PT	AU	BA	BE	GP	AF	BF	CA	TI	SO	SE	BS	LA	DT	CT	CY	CL	SP	HO	DE	ID	AB	C1	RP	EM	RI	OI	FU	FX	CR	NR	TC	Z9	U1	U2	PU	PI	PA	SN	EI	BN	J9	JI	PD	PY	VL	IS	PN	SU	SI	MA	BP	EP	AR	DI	D2	EA	PG	WC	SC	GA	UT	PM	OA	HC	HP	DA
J	Deckl, P; Weydt, P; Thal, DR; Weishaupt, JH; Ludolph, AC; Otto, M				Deckl, Patrick; Weydt, Patrick; Thal, Dietmar R.; Weishaupt, Jochen H.; Ludolph, Albert C.; Otto, Markus			Proteomics in cerebrospinal fluid and spinal cord suggests UCHL1, MAP2 and GPNMB as biomarkers and underpins importance of transcriptional pathways in amyotrophic lateral sclerosis	ACTA NEUROPATHOLOGICA												Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and the proteins and pathways involved in the pathophysiology are not fully understood. Even less is known about the preclinical disease phase. To uncover new ALS-related proteins and pathways, we performed a comparative proteomic analysis in cerebrospinal fluid (CSF) of asymptomatic (n = 14) and symptomatic (n = 14) ALS mutation carriers and sporadic ALS patients (n = 12) as well as post-mortem human spinal cord tissue (controls: n = 7, ALS, n = 8). Using a CSF-optimized proteomic workflow, we identified novel (e.g., UCHL1, MAP2, CAPG, GPNMB, HIST1H4A, HIST1H2B) and well-described (e.g., NEFL, NEFH, NEFM, CHIT1, CHI3L1) protein level changes in CSF of sporadic and genetic ALS patients with enrichment of proteins related to transcription, cell cycle and lipoprotein remodeling (total protein IDs: 2303). No significant alteration was observed in asymptomatic ALS mutation carriers representing the prodromal disease phase. We confirmed UCHL1, MAP2, CAPG and GPNMB as novel biomarker candidates for ALS in an independent validation cohort of patients (n = 117) using multiple reaction monitoring. In spinal cord tissue, 292 out of 6810 identified proteins were significantly changed in ALS with enrichment of proteins involved in mRNA splicing and of the neurofilament compartment. In conclusion, our proteomic data in asymptomatic ALS mutation carriers support the hypothesis of a sudden disease onset instead of a long preclinical phase. Both CSF and tissue proteomic data indicate transcriptional pathways to be amongst the most affected. UCHL1, MAP2 and GPNMB are promising ALS biomarker candidates which might provide additional value to the established neurofilaments in patient follow-up and clinical trials.				Thal, Dietmar/O-7483-2018	Thal, Dietmar/0000-0002-1036-1075												0001-6322	1432-0533															10.1007/s00401-019-02093-x		NOV 2019					WOS:000495024500001	31701227					
J	Mayeuf-Louchart, A; Lancel, S; Sebti, Y; Pourcet, B; Loyens, A; Delhaye, S; Duhem, C; Beauchamp, J; Ferri, L; Thorel, Q; Boulinguiez, A; Zecchin, M; Dubois-Chevalier, J; Eeckhoute, J; Vaughn, LT; Roach, PJ; Dani, C; Pederson, BA; Vincent, SD; Staels, B; Duez, H				Mayeuf-Louchart, Alicia; Lancel, Steve; Sebti, Yasmine; Pourcet, Benoit; Loyens, Anne; Delhaye, Stephane; Duhem, Christian; Beauchamp, Justine; Ferri, Lise; Thorel, Quentin; Boulinguiez, Alexis; Zecchin, Mathilde; Dubois-Chevalier, Julie; Eeckhoute, Jerome; Vaughn, Logan T.; Roach, Peter J.; Dani, Christian; Pederson, Bartholomew A.; Vincent, Stephane D.; Staels, Bart; Duez, Helene			Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation	CELL REPORTS												Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs.					Dani, Christian/0000-0003-3228-0230												2211-1247					NOV 5	2019	29	6					1410	+		10.1016/j.celrep.2019.09.073							WOS:000495045400002	31693883					
J	Yan, XB; Ramos, RANS; Alcouffe, P; Munoz, LE; Bilyy, RO; Ganachaud, F; Bernard, J				Yan, Xibo; Ramos, Ricardo Almeida Neves Sampayo; Alcouffe, Pierre; Munoz, Luis E.; Bilyy, Rostyslav O.; Ganachaud, Francois; Bernard, Julien			Programmable Hierarchical Construction of Mixed/Multilayered Polysaccharide Nanocapsules through Simultaneous/Sequential Nanoprecipitation Steps	BIOMACROMOLECULES												We report here on a one-pot construction of oil filled hierarchical capsular assemblies using the nanoprecipitation technique. Relying on multicomponent phase diagrams, we show that simultaneous and/or sequential nanoprecipitations involving polymer combinations can be precisely programmed to design a new class of mixed/multilayered multicomponent nanocapsules, with a precise control of the dimensions, shell thickness/composition, and spatial distribution of the building blocks. The simplicity and tunability of this approach are exemplified here with a library of neutral and ionic polysaccharides giving access to a range of functional multilayered nanocarriers of interest for biomedical applications.					Bernard, Julien/0000-0002-9969-1686												1525-7797	1526-4602				OCT	2019	20	10					3915	3923		10.1021/acs.biomac.9b00990							WOS:000490658900029	31479237					
J	Munoz, LE; Boeltz, S; Bilyy, R; Schauer, C; Mahajan, A; Widulin, N; Gruneboom, A; Herrmann, I; Boada, E; Rauh, M; Krenn, V; Biermann, MHC; Podolska, MJ; Hahn, J; Knopf, J; Maueroder, C; Paryzhak, S; Dumych, T; Zhao, Y; Neurath, MF; Hoffmann, MH; Fuchs, TA; Leppkes, M; Schett, G; Herrmann, M				Munoz, Luis E.; Boeltz, Sebastian; Bilyy, Rostyslav; Schauer, Christine; Mahajan, Aparna; Widulin, Navena; Grueneboom, Anika; Herrmann, Irmgard; Boada, Edgyda; Rauh, Manfred; Krenn, Veit; Biermann, Mona H. C.; Podolska, Malgorzata J.; Hahn, Jonas; Knopf, Jasmin; Maueroeder, Christian; Paryzhak, Solomiya; Dumych, Tetiana; Zhao, Yi; Neurath, Markus F.; Hoffmann, Markus H.; Fuchs, Tobias A.; Leppkes, Moritz; Schett, Georg; Herrmann, Martin			Neutrophil Extracellular Traps Initiate Gallstone Formation	IMMUNITY												The presence of gallstones (cholelithiasis) is a highly prevalent and severe disease and one of the leading causes of hospital admissions worldwide. Due to its substantial health impact, we investigated the biological mechanisms that lead to the formation and growth of gallstones. We show that gallstone assembly essentially requires neutrophil extracellular traps (NETs). We found consistent evidence for the presence of NETs in human and murine gallstones and describe an immune-mediated process requiring activation of the innate immune system for the formation and growth of gallstones. Targeting NET formation via inhibition of peptidyl arginine deiminase type 4 or abrogation of reactive oxygen species (ROS) production, as well as damping of neutrophils by metoprolol, effectively inhibit gallstone formation in vivo. Our results show that after the physicochemical process of crystal formation, NETs foster their assembly into larger aggregates and finally gallstones. These insights provide a feasible therapeutic concept to prevent cholelithiasis in patients at risk.				Maueroder, Christian/H-7412-2016; Boeltz, Sebastian/H-3594-2014	Maueroder, Christian/0000-0002-7563-883X; Boeltz, Sebastian/0000-0001-5227-8707; Hahn, Jonas/0000-0003-3944-2108												1074-7613	1097-4180				SEP 17	2019	51	3					443	+		10.1016/j.immuni.2019.07.002							WOS:000486184600008	31422870					
J	Li, CN; Pagneux, Q; Voronova, A; Barras, A; Abderrahmani, A; Plaisance, V; Pawlowski, V; Hennuyer, N; Staels, B; Rosselle, L; Skandrani, N; Li, MS; Boukherroub, R; Szunerits, S				Li Chengnan; Pagneux, Quentin; Voronova, Anna; Barras, Alexandre; Abderrahmani, Amar; Plaisance, Valerie; Pawlowski, Valerie; Hennuyer, Nathalie; Staels, Bart; Rosselle, Lea; Skandrani, Nadia; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine			Near-infrared light activatable hydrogels for metformin delivery	NANOSCALE												Drug loaded hydrogels have proven to be versatile controlled-release systems. We report here on heat active hydrogel formation by mixing graphene oxide (GO) or carboxyl enriched reduced graphene oxide (rGO-COOH) with metformin hydrochloride, an insulin sensitizer drug currently used as the first line therapy to treat patients with type 2 diabetes. The driving forces of the gelation process between the graphene- based nanomaterial and metformin are hydrogen bonding and electrostatic interactions, weakened at elevated temperature. Using the excellent photothermal properties of the graphene matrixes, we demonstrate that these supramolecular drug reservoirs can be photothermally activated for transdermal metformin delivery. A sustained delivery of metformin was achieved using a laser power of 1 W cm-2. In vitro assessment of the key target Glucose-6 Phosphatase (G6P) gene expression using a human hepatocyte model confirmed that metformin activity was unaffected by photothermal activation. In vivo, metformin was detected in mice plasma at 1 h post-activation of the metformin loaded rGO-COOH gel.				Abderrahmani, Amar/O-3124-2017	Abderrahmani, Amar/0000-0003-0752-0343												2040-3364	2040-3372				SEP 14	2019	11	34					15810	15820		10.1039/c9nr02707f							WOS:000483691300039	31270521					
J	Nyazika, T; Jimenez, M; Samyn, F; Bourbigot, S				Nyazika, Tatenda; Jimenez, Maude; Samyn, Fabienne; Bourbigot, Serge			Pyrolysis modeling, sensitivity analysis, and optimization techniques for combustible materials: A review	JOURNAL OF FIRE SCIENCES												Over the past years, pyrolysis models have moved from thermal models to comprehensive models with great flexibility including multi-step decomposition reactions. However, the downside is the need for a complete set of input data such as the material properties and the parameters related to the decomposition kinetics. Some of the parameters are not directly measurable or are difficult to determine and they carry a certain degree of uncertainty at high temperatures especially for materials that can melt, shrink, or swell. One can obtain input parameters by searching through the literature; however, certain materials may have the same nomenclature but the material properties may vary depending on the manufacturer, thereby inducing uncertainties in the model. Modelers have resorted to the use of optimization techniques such as gradient-based and direct search methods to estimate input parameters from experimental bench-scale data. As an integral part of the model, a sensitivity study allows to identify the role of each input parameter on the outputs. This work presents an overview of pyrolysis modeling, sensitivity analysis, and optimization techniques used to predict the fire behavior of combustible solids when exposed to an external heat flux.					Bourbigot, Serge/0000-0003-1536-2015												0734-9041	1530-8049														UNSP 0734904119852740	10.1177/0734904119852740		SEP 2019					WOS:000485082400001						
J	Hahn, J; Euler, M; Kilgus, E; Kienhofer, D; Stoof, J; Knopf, J; Hahn, M; Harrer, T; Hultqvist, M; Olofsson, P; Mokhir, A; Holmdahl, R; Herrmann, M; Schett, G; Munoz, LE; Hoffmann, MH				Hahn, Jonas; Euler, Maximilien; Kilgus, Emelie; Kienhoefer, Deborah; Stoof, Julia; Knopf, Jasmin; Hahn, Madelaine; Harrer, Thomas; Hultqvist, Malin; Olofsson, Peter; Mokhir, Andriy; Holmdahl, Rikard; Herrmann, Martin; Schett, Georg; Munoz, Luis E.; Hoffmann, Markus H.			NOX2 mediates quiescent handling of dead cell remnants in phagocytes	REDOX BIOLOGY												The phagocyte NADPH oxidase (the NOX2 complex) generates superoxide, the precursor to reactive oxygen species (ROS). ROS possess both antimicrobial and immunoregulatory function. Inactivating mutations in alleles of the NOX2 complex cause chronic granulomatous disease (CGD), characterized by an enhanced susceptibility to infections and autoimmune diseases such as Systemic lupus erythematosus (SLE). The latter is characterized by insufficient removal of dead cells, resulting in an autoimmune response against components of the cell's nucleus when non-cleared apoptotic cells lose their membrane integrity and present autoantigenic molecules in an inflammatory context. Here we aimed to shed light on the role of the NOX2 complex in handling of secondary necrotic cells (SNECs) and associated consequences for inflammation and autoimmunity during lupus. We show that individuals with SLE and CGD display accumulation of SNECs in blood monocytes and neutrophils. In a CGD phenotypic mouse strain (Ncf1** mice) build-up of SNECs in Ly6C(HI) blood monocytes was connected with a delayed degradation of the phagosomal cargo and accompanied by production of inflammatory mediators. Treatment with H2O2 or activators of ROS-formation reconstituted phagosomal abundance of SNECs to normal levels. Induction of experimental lupus further induced increased antibody-dependent uptake of SNECs into neutrophils. Lupus-primed Ncf1** neutrophils took up more SNECs than wild type neutrophils, whereas SNEC-accumulation in regulatory Ly6C(-/LO) monocytes was lower in Ncf1**mice. We deduce that the inflammatory rerouting of immune-stimulatory necrotic material into inflammatory phagocyte subsets contributes to the connection between low ROS production by the NOX2 complex and SLE.					Hahn, Jonas/0000-0003-3944-2108												2213-2317					SEP	2019	26								UNSP 101279	10.1016/j.redox.2019.101279							WOS:000493821500036	31349119					
J	Hopfner, F; Hobert, MA; Maetzler, C; Hansen, C; Pham, MH; Moreau, C; Berg, D; Devos, D; Maetzler, W				Hopfner, Franziska; Hobert, Markus A.; Maetzler, Corina; Hansen, Clint; Minh Hoang Pham; Moreau, Caroline; Berg, Daniela; Devos, David; Maetzler, Walter		Fair-Park II Study Grp	Mobility Deficits Assessed With Mobile Technology: What Can We Learn From Brain Iron-Altered Animal Models?	FRONTIERS IN NEUROLOGY												Background: Recent developments inmobile technology have enabled the investigation of human movements and mobility under natural conditions, i.e., in the home environment. Iron accumulation in the basal ganglia is deleterious in Parkinson's disease (i.e., iron accumulation with lower striatal level of dopamine). The effect of iron chelation (i.e., re-deployment of iron) in Parkinson's disease patients is currently tested in a large investigator-initiated multicenter study. Conversely, restless legs syndrome (RLS) is associated with iron depletion and higher striatal level of dopamine. To determine from animal models which movement and mobility parameters might be associated with iron content modulation and the potential effect of therapeutic chelation inhuman. Methods: We recapitulated pathophysiological aspects of the association between iron, dopamine, and neuronal dysfunction and deterioration in the basal ganglia, and systematically searched PubMed to identify original articles reporting about quantitatively assessed mobility deficits in animal models of brain iron dyshomeostasis. Results: We found six original studies using murine and fly models fulfilling the inclusion criteria. Especially postural and trunk stability were altered in animal models with iron overload. Animal models with lowered basal ganglia iron suffered from alterations in physical activity, mobility, and sleep fragmentation. Conclusion: From preclinical investigations in the animal model, we can deduce that possibly also in humans with iron accumulation in the basal ganglia undergoing therapeutic chelation may primarily show changes in physical activity (such as daily "motor activity"), postural and trunk stability and sleep fragmentation. These changes can readily be monitored with currently available mobile technology.				Berg, Daniela D/A-8728-2019	Berg, Daniela D/0000-0001-5796-5442												1664-2295					AUG 8	2019	10								833	10.3389/fneur.2019.00833							WOS:000479228100001	31440200					
J	Addad, A; Carrez, P; Cordier, P; Jacob, D; Karato, SI; Mohiuddin, A; Mussi, A; Nzogang, BC; Roussel, P; Tommasi, A				Addad, A.; Carrez, P.; Cordier, P.; Jacob, D.; Karato, S-, I; Mohiuddin, A.; Mussi, A.; Nzogang, B. C.; Roussel, P.; Tommasi, A.			Anhydrous Phase B: Transmission Electron Microscope Characterization and Elastic Properties	GEOCHEMISTRY GEOPHYSICS GEOSYSTEMS												We have performed an extensive characterization by transmission electron microscopy (including precession electron diffraction tomography and ab initio electron diffraction refinement as well as electron energy loss spectroscopy) of anhydrous phase B (Anh-B) formed directly from olivine at 14 GPa, 1400 degrees C. We show that Anh-B, which can be considered as a superstructure of olivine, exhibits strong topotactic relationships with it. This lowers the interfacial energy between the two phases and the energy barrier for nucleation of Anh-B, which can form as a metastable phase. We have calculated the elastic and seismic properties of Anh-B. From the elastic point of view, Anh-B appears to be more isotropic than olivine. Anh-B displays only a moderate seismic anisotropy quite similar to the one of wadsleyite.				; Jacob, Damien/N-8419-2013; MUSSI, Alexandre/N-9476-2013; Cordier, Patrick/D-2357-2012	Roussel, Pascal/0000-0001-7243-7293; Jacob, Damien/0000-0001-7931-7171; Tommasi, Andrea/0000-0002-6457-1852; Karato, Shun-ichiro/0000-0002-1483-4589; MUSSI, Alexandre/0000-0003-2093-0144; Cordier, Patrick/0000-0002-1883-2994; MOHIUDDIN, ANWAR/0000-0002-6058-4891													1525-2027				AUG	2019	20	8					4059	4072		10.1029/2019GC008429							WOS:000490955300015	31762710					
J	Geoffroy, L; Samyn, F; Jimenez, M; Bourbigot, S				Geoffroy, Laura; Samyn, Fabienne; Jimenez, Maude; Bourbigot, Serge			Additive manufacturing of fire-retardant ethylene-vinyl acetate	POLYMERS FOR ADVANCED TECHNOLOGIES												Thermocompression (with also extrusion and injection molding) is a classical polymer shaping manufacturing, but it does not easily allow designing sophisticated shapes without using a complex mold, on the contrary to 3D printing (or polymer additive manufacturing), which is a very flexible technique. Among all 3D printing techniques, fused deposition modeling is of high potential for product manufacturing, with the capability to compete with conventional polymer processing techniques. This is a quite low cost 3D printing technique, but the range of filaments commercially available is limited. However, in some specific 3D printing processes, no filaments are necessary. Polymers pellets feed directly the printing nozzle allowing to investigate many polymeric matrices with no commercial limitation. This is of high interest for the design of flame-retarded materials, but literature is scarce in that field. In this paper, a comparison between thermocompression and 3D printing processes was performed on both neat ethylene-vinyl acetate (EVA) copolymer and EVA flame retarded with aluminum triHydroxyde (ATH) containing different loadings (30 or 65 wt%) and with expandable graphite (EG), ie, EVA/ATH (30 wt%), EVA/ATH (65 wt%), and EVA/EG (10 wt%), respectively. Morphological comparisons, using microscopic and electronic microprobe analyses, revealed that 3D printed plates have lower apparent density and higher porosity than thermocompressed plate. The fire-retardant properties of thermocompressed and 3D printed plates were then evaluated using mass loss calorimeter test at 50 kW/m(2). Results highlight that 3D printing can be used to produce flame-retardant systems. This work is a pioneer study exploring the feasibility of using polymer additive manufacturing technology for designing efficient flame-retarded materials.					Bourbigot, Serge/0000-0003-1536-2015; GEOFFROY, Laura/0000-0002-0834-2000												1042-7147	1099-1581				JUL	2019	30	7					1878	1890		10.1002/pat.4620							WOS:000472523900035						
J	Mukherji, A; Bailey, SM; Staels, B; Baumert, TF				Mukherji, Atish; Bailey, Shannon M.; Staels, Bart; Baumert, Thomas F.			The circadian clock and liver function in health and disease	JOURNAL OF HEPATOLOGY												Each day, all organisms are subjected to changes in light intensity because of the Earth's rotation around its own axis. To anticipate this geo-physical variability, and to appropriately respond biochemically, most species, including mammals, have evolved an approximate 24-hour endogenous timing mechanism known as the circadian clock (CC). The 'clock' is self-sustained, cell autonomous and present in every cell type. At the core of the clock resides the CC-oscillator, an exquisitely crafted transcriptional-translational feedback system. Remarkably, components of the CC-oscillator not only maintain daily rhythmicity of their own synthesis, but also generate temporal variability in the expression levels of numerous target genes through transcriptional, post-transcriptional and post-translational mechanisms, thus, ensuring proper chronological coordination in the functioning of cells, tissues and organs, including the liver. Indeed, a variety of physiologically critical hepatic functions and cellular processes are CC-controlled. Thus, it is not surprising that modern lifestyle factors (e.g. travel and jet lag, night and rotating shift work), which force 'circadian misalignment', have emerged as major contributors to global health problems including obesity, non-alcoholic fatty liver disease and steatohepatitis. Herein, we provide an overview of the CC-dependent pathways which play critical roles in mediating several hepatic functions under physiological conditions, and whose deregulation is implicated in chronic liver diseases including non-alcoholic steatohepatitis and alcohol-related liver disease. (C) 2019 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.				Staels, Bart/N-9497-2016	Staels, Bart/0000-0002-3784-1503												0168-8278	1600-0641				JUL	2019	71	1					200	211		10.1016/j.jhep.2019.03.020							WOS:000471646900021	30930223					
J	Margerie, D; Lefebvre, P; Raverdy, V; Schwahn, U; Ruetten, H; Larsen, P; Duhamel, A; Labreuche, J; Thuillier, D; Derudas, B; Gheeraert, C; Dehondt, H; Dhalluin, Q; Alexandre, J; Caiazzo, R; Nesslany, P; Verkindt, H; Pattou, F; Staels, B				Margerie, Daniel; Lefebvre, Philippe; Raverdy, Violeta; Schwahn, Uwe; Ruetten, Hartmut; Larsen, Philip; Duhamel, Alain; Labreuche, Julien; Thuillier, Dorothee; Derudas, Bruno; Gheeraert, Celine; Dehondt, Helene; Dhalluin, Quentin; Alexandre, Jeremy; Caiazzo, Robert; Nesslany, Pamela; Verkindt, Helene; Pattou, Francois; Staels, Bart			Hepatic transcriptomic signatures of statin treatment are associated with impaired glucose homeostasis in severely obese patients	BMC MEDICAL GENOMICS												BackgroundClinical data identified an association between the use of HMG-CoA reductase inhibitors (statins) and incident diabetes in patients with underlying diabetes risk factors such as obesity, hypertension and dyslipidemia. The molecular mechanisms however are unknown.MethodsAn observational cross-sectional study included 910 severely obese patients, mean (SD) body mass index (BMI) 46.7 (8.7), treated with or without statins (ABOS cohort: a biological atlas of severe obesity). Data and sample collection took place in France between 2006 and 2016. Transcriptomic signatures of statin treatment in human liver obtained from genome-wide transcriptomic profiling of five different statin drugs using microarrays were correlated to clinico-biological phenotypes and also assigned to biological pathways and mechanisms. Patients from the non-statin-users group were matched to patients in the statin users group by propensity score analysis to minimize confounding effects from age, gender, parental familial history of diabetes, BMI, waist circumference, systolic and diastolic blood pressure and use of anti-hypertensive drugs as pre-specified covariates.ResultsWe determined the hepatic, statin-related gene signature from genome-wide transcriptomic profiling in severely obese patients with varying degrees of glucose tolerance and cardio-metabolic comorbidities. One hundred and fifty seven patients on statin treatment in the matched cohort showed higher diabetes prevalence (OR = 2.67; 95%CI, 1.60-4.45; P = 0.0002) and impairment of glucose homeostasis. This phenotype was associated with molecular signatures of increased hepatic de novo lipogenesis (DNL) via activation of sterol regulatory element-binding protein 1 (SREBP1) and concomitant upregulation of the expression of key genes in both fatty acid and triglyceride metabolism.ConclusionsA DNL gene activation profile in response to statins is associated with insulin resistance and the diabetic status of the patients. Identified molecular signatures thus suggest that statin treatment increases the risk for diabetes in humans at least in part via induction of DNL.Trial registrationNCT01129297. Registered May 242,010 (retrospectively registered).				Staels, Bart/N-9497-2016; Pattou, Francois/Y-8448-2019; caiazzo, robert/Y-9692-2019	Staels, Bart/0000-0002-3784-1503; caiazzo, robert/0000-0001-5383-0540												1755-8794					JUN 3	2019	12								80	10.1186/s12920-019-0536-1							WOS:000470111200001	31159817					
J	Chavez-Talavera, O; Haas, J; Grzych, G; Tailleux, A; Staels, B				Chavez-Talavera, Oscar; Haas, Joel; Grzych, Guillaume; Tailleux, Anne; Staels, Bart			Bile acid alterations in nonalcoholic fatty liver disease, obesity, insulin resistance and type 2 diabetes: what do the human studies tell?	CURRENT OPINION IN LIPIDOLOGY												Purpose of review The purpose of this review is to discuss the influence of obesity, insulin resistance, type 2 diabetes (T2D), and nonalcoholic fatty liver disease (NAFLD) on bile acid metabolism and to analyze whether these findings reinforce current beliefs about the role of bile acids in the pathophysiology of these diseases. Recent findings Discordant results on plasma bile acid alterations in NAFLD patients have been reported. Obesity, insulin resistance, and T2D, common comorbidities of NAFLD, have been associated with bile acid changes, but the individual bile acid species variations differ between studies (summarized in this review), perhaps because of clinicobiological differences between the studied patient populations and the heterogeneity of statistical analyses applied. Summary The regulatory role of bile acids in metabolic and cellular homeostasis renders bile acids attractive candidates as players in the pathophysiology of NAFLD. However, considering the complex relationship between NAFLD, obesity, insulin resistance and T2D, it is difficult to establish clear and independent associations between bile acid alterations and these individual diseases. Though bile acid alterations may not drive NAFLD progression, signaling pathways activated by bile acids remain potent therapeutic targets for its treatment. Further studies with appropriate matching or adjustment for potential confounding factors are necessary to determine which pathophysiological conditions drive the alterations in bile acid metabolism.				GRZYCH, Guillaume GG/C-8094-2019; Staels, Bart/N-9497-2016	Staels, Bart/0000-0002-3784-1503; Grzych, Guillaume/0000-0003-2813-0109; Haas, Joel/0000-0002-0028-5988												0957-9672	1473-6535				JUN	2019	30	3					244	254		10.1097/MOL.0000000000000597							WOS:000467647900013	30893108					
J	Mogilenko, DA; Haas, JT; L'homme, L; Fleury, S; Quemener, S; Levavasseur, M; Becquart, C; Wartelle, J; Bogomolova, A; Pineau, L; Molendi-Coste, O; Lancel, S; Dehondt, H; Gheeraert, C; Melchior, A; Dewas, C; Nikitin, A; Pic, S; Rabhi, N; Annicotte, JS; Oyadomari, S; Velasco-Hernandez, T; Cammenga, J; Foretz, M; Viollet, B; Vukovic, M; Villacreces, A; Kranc, K; Carmeliet, P; Marot, G; Boulter, A; Tavernier, S; Berod, L; Longhi, MP; Paget, C; Janssens, S; Staumont-Salle, D; Aksoy, E; Staels, B; Dombrowicz, D				Mogilenko, Denis A.; Haas, Joel T.; L'homme, Laurent; Fleury, Sebastien; Quemener, Sandrine; Levavasseur, Matthieu; Becquart, Coralie; Wartelle, Julien; Bogomolova, Alexandra; Pineau, Laurent; Molendi-Coste, Olivier; Lancel, Steve; Dehondt, Helene; Gheeraert, Celine; Melchior, Aurelie; Dewas, Cedric; Nikitin, Artemii; Pic, Samuel; Rabhi, Nabil; Annicotte, Jean-Sebastien; Oyadomari, Seiichi; Velasco-Hernandez, Talia; Cammenga, Jorg; Foretz, Marc; Viollet, Benoit; Vukovic, Milica; Villacreces, Arnaud; Kranc, Kamil; Carmeliet, Peter; Marot, Guillemette; Boulter, Alexis; Tavernier, Simon; Berod, Luciana; Longhi, Maria P.; Paget, Christophe; Janssens, Sophie; Staumont-Salle, Delphine; Aksoy, Ezra; Staels, Bart; Dombrowicz, David			Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR	CELL												Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-like receptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatory signals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect the immune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DCs) are exacerbated by a high-fatty-acid (FA) metabolic environment. FAs suppress the TLR-induced hexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changes enhance mitochondria! reactive oxygen species (mtROS) production and, in turn, the unfolded protein response (UPR), leading to a distinct transcriptomic signature with IL-23 as hallmark. Interestingly, chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response. Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23 expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innate immunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.				Tavernier, Simon/L-9949-2019; Velasco-Hernandez, Talia/AAD-9753-2019; Staels, Bart/N-9497-2016; L'homme, Laurent/I-8099-2019; Dombrowicz, David/F-7044-2013; Viollet, Benoit/O-6927-2017; Annicotte, Jean-Sebastien/H-4641-2018; Paget, Christophe/P-5165-2014	Tavernier, Simon/0000-0003-2514-5655; Velasco-Hernandez, Talia/0000-0003-2183-7443; Staels, Bart/0000-0002-3784-1503; L'homme, Laurent/0000-0002-5069-1837; Dombrowicz, David/0000-0002-0485-8923; Viollet, Benoit/0000-0002-0121-0224; Haas, Joel/0000-0002-0028-5988; Aksoy, Ezra/0000-0002-6962-1572; Lancel, Steve/0000-0002-3292-5433; Annicotte, Jean-Sebastien/0000-0002-2109-4849; Paget, Christophe/0000-0002-5374-5407												0092-8674	1097-4172				MAY 16	2019	177	5					1201	+		10.1016/j.cell.2019.03.018							WOS:000468103800013	31031005					
J	Budimir, M; Jijie, R; Ye, R; Barras, A; Melinte, S; Silhanek, A; Markovic, Z; Szunerits, S; Boukherroub, R				Budimir, Milica; Jijie, Roxana; Ye, Ran; Barras, Alexandre; Melinte, Sorin; Silhanek, Alejandro; Markovic, Zoran; Szunerits, Sabine; Boukherroub, Rabah			Efficient capture and photothermal ablation of planktonic bacteria and biofilms using reduced graphene oxide-polyethyleneimine flexible nanoheaters	JOURNAL OF MATERIALS CHEMISTRY B												Bacterial infections are one of the leading causes of disease worldwide. Conventional antibiotics are becoming less efficient, due to antibiotic-resistant bacterial strains. Therefore, the development of novel antibacterial materials and advanced treatment strategies are becoming increasingly important. In the present work, we developed a simple and efficient strategy for effective bacterial capture and their subsequent eradication through photothermal killing. The developed device consists of a flexible nanoheater, comprising a Kapton/Au nanoholes substrate, coated with reduced graphene oxide-polyethyleneimine (K/Au NH/rGO-PEI) thin films. The Au NH plasmonic structure was tailored to feature strong absorption in the near-infrared (NIR) region, where most biological matter has limited absorption, while PEI was investigated for its strong binding with bacteria through electrostatic interactions. The K/Au NH/rGO-PEI device was demonstrated to capture and eliminate effectively both planktonic Gram-positive Staphilococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria after 10 min of NIR (980 nm) irradiation and, to destroy and eradicate Staphilococcus epidermidis (S. epidermidis) biofilms after 30 min irradiation. The technique developed herein is simple and universal with potential applications for eradication of different micro-organisms.				Jijie, Roxana/N-6837-2017	Jijie, Roxana/0000-0003-0354-943X; Szunerits, Sabine/0000-0002-1567-4943; Markovic, Zoran/0000-0001-5917-4337; Budimir, Milica/0000-0003-0742-0983												2050-750X	2050-7518				MAY 7	2019	7	17					2771	2781		10.1039/c8tb01676c							WOS:000471328500014						
J	Molinaro, A; Caesar, R; L'homme, L; Koh, A; Stahlman, M; Staels, B; Backhed, F				Molinaro, Antonio; Caesar, Robert; L'homme, Laurent; Koh, Ara; Stahlman, Marcus; Staels, Bart; Backhed, Fredrik			Liver-specific ROR alpha deletion does not affect the metabolic susceptibility to western style diet feeding	MOLECULAR METABOLISM												Objectives: The nuclear receptor superfamily is a potential target for the development of new treatments for obesity and metabolic diseases. Increasing evidence has pointed towards the retinoic acid-related orphan receptor-alpha (ROR alpha) as an important nuclear receptor involved in several biological processes. ROR alpha full body knockout mice display improved metabolic phenotypes on both chow and high fat (60% fat, 20% carbohydrate) diets, but also have severe behavioral abnormalities. Here we investigated the effect of hepatic ROR alpha by generating mice with liver-specific ROR alpha deletion to elucidate the role of this nuclear receptor on host metabolism. Methods: 8 week-old mice with liver-specific ROR alpha deletion and littermate controls were fed either chow or western-style diets (40% fat, 40% carbohydrate) for 12 weeks. Metabolic phenotyping was performed at the end of the dietary intervention. Results: Here, we show that hepatic ROR alpha deletion does not affect the metabolic susceptibility to either chow or western-style diet in terms of glucose metabolism and adiposity. Conclusions: Our data indicate that liver deletion of ROR alpha does not have a pivotal role in the regulation of hepatic glucose and lipid metabolism on chow or western-style diet. (C) 2019 The Authors. Published by Elsevier GmbH.				Staels, Bart/N-9497-2016; L'homme, Laurent/I-8099-2019	Staels, Bart/0000-0002-3784-1503; L'homme, Laurent/0000-0002-5069-1837												2212-8778					MAY	2019	23						82	87		10.1016/j.molmet.2019.02.010							WOS:000464989600008	30904385					
J	Paumelle, R; Haas, JT; Hennuyer, N; Bauge, E; Deleye, Y; Mesotten, D; Langouche, L; Vanhoutte, J; Cudejko, C; Wouters, K; Hannou, SA; Legry, V; Lancel, S; Lalloyer, F; Polizzi, A; Smati, S; Gourdy, P; Vallez, E; Bouchaert, E; Derudas, B; Dehondt, H; Gheeraert, C; Fleury, S; Tailleux, A; Montagner, A; Wahli, W; Van den Berghe, G; Guillou, H; Dombrowicz, D; Staels, B				Paumelle, Rejane; Haas, Joel T.; Hennuyer, Nathalie; Bauge, Eric; Deleye, Yann; Mesotten, Dieter; Langouche, Lies; Vanhoutte, Jonathan; Cudejko, Celine; Wouters, Kristiaan; Hannou, Sarah Anissa; Legry, Vanessa; Lancel, Steve; Lalloyer, Fanny; Polizzi, Arnaud; Smati, Sarra; Gourdy, Pierre; Vallez, Emmanuelle; Bouchaert, Emmanuel; Derudas, Bruno; Dehondt, Helene; Gheeraert, Celine; Fleury, Sebastien; Tailleux, Anne; Montagner, Alexandra; Wahli, Walter; Van den Berghe, Greet; Guillou, Herve; Dombrowicz, David; Staels, Bart			Hepatic PPAR alpha is critical in the metabolic adaptation to sepsis	JOURNAL OF HEPATOLOGY												Background & Aims: Although the role of inflammation to combat infection is known, the contribution of metabolic changes in response to sepsis is poorly understood. Sepsis induces the release of lipid mediators, many of which activate nuclear receptors such as the peroxisome proliferator-activated receptor (PPAR)alpha, which controls both lipid metabolism and inflammation. We aimed to elucidate the previously unknown role of hepatic PPAR alpha in the response to sepsis. Methods: Sepsis was induced by intraperitoneal injection of Escherichia coli in different models of cell-specific PPAR alpha-deficiency and their controls. The systemic and hepatic metabolic response was analyzed using biochemical, transcriptomic and functional assays. PPAR alpha expression was analyzed in livers from elective surgery and critically ill patients and correlated with hepatic gene expression and blood parameters. Results: Both whole body and non-hematopoietic PPAR alpha-deficiency in mice decreased survival upon bacterial infection. Livers of septic PPAR alpha-deficient mice displayed an impaired metabolic shift from glucose to lipid utilization resulting in more severe hypoglycemia, impaired induction of hyperketonemia and increased steatosis due to lower expression of genes involved in fatty acid catabolism and ketogenesis. Hepatocyte-specific deletion of PPAR alpha impaired the metabolic response to sepsis and was sufficient to decrease survival upon bacterial infection. Hepatic PPAR alpha expression was lower in critically ill patients and correlated positively with expression of lipid metabolism genes, but not with systemic inflammatory markers. Conclusion: During sepsis, PPAR alpha-deficiency in hepatocytes is deleterious as it impairs the adaptive metabolic shift from glucose to FA utilization. Metabolic control by PPAR alpha in hepatocytes plays a key role in the host defense against infection. Lay summary: As the main cause of death in critically ill patients, sepsis remains a major health issue lacking efficacious therapies. While current clinical literature suggests an important role for inflammation, metabolic aspects of sepsis have mostly been overlooked. Here, we show that mice with an impaired metabolic response, due to deficiency of the nuclear receptor PPAR alpha in the liver, exhibit enhanced mortality upon bacterial infection despite a similar inflammatory response, suggesting that metabolic interventions may be a viable strategy for improving sepsis outcomes. (C) 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.				Dombrowicz, David/F-7044-2013; , Lancel/H-9047-2019; Wouters, Kristiaan/A-8536-2013; Langouche, Lies/C-1098-2013; Staels, Bart/N-9497-2016	Dombrowicz, David/0000-0002-0485-8923; , Lancel/0000-0002-3292-5433; Wouters, Kristiaan/0000-0001-7127-6950; Langouche, Lies/0000-0002-8564-6809; Staels, Bart/0000-0002-3784-1503; Hannou, sarah/0000-0003-4780-5773; Van den Berghe, Greet/0000-0002-5320-1362; Haas, Joel/0000-0002-0028-5988												0168-8278	1600-0641				MAY	2019	70	5					963	973		10.1016/j.jhep.2018.12.037							WOS:000464016500019	30677458					
J	Liang, N; Damdimopoulos, A; Goni, S; Huang, ZQ; Vedin, LL; Jakobsson, T; Giudici, M; Ahmed, O; Pedrelli, M; Barilla, S; Alzaid, F; Mendoza, A; Schroder, T; Kuiper, R; Parini, P; Hollenberg, A; Lefebvre, P; Francque, S; Van Gaal, L; Staels, B; Venteclef, N; Treuter, E; Fan, RR				Liang, Ning; Damdimopoulos, Anastasius; Goni, Saioa; Huang, Zhiqiang; Vedin, Lise-Lotte; Jakobsson, Tomas; Giudici, Marco; Ahmed, Osman; Pedrelli, Matteo; Barilla, Serena; Alzaid, Fawaz; Mendoza, Arturo; Schroder, Tarja; Kuiper, Raoul; Parini, Paolo; Hollenberg, Anthony; Lefebvre, Philippe; Francque, Sven; Van Gaal, Luc; Staels, Bart; Venteclef, Nicolas; Treuter, Eckardt; Fan, Rongrong			Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPAR alpha	NATURE COMMUNICATIONS												Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor alpha (PPAR alpha, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPAR alpha partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.				Staels, Bart/N-9497-2016; Fan, Rongrong/N-3446-2017	Staels, Bart/0000-0002-3784-1503; Fan, Rongrong/0000-0002-5707-1497												2041-1723					APR 11	2019	10								1684	10.1038/s41467-019-09524-z							WOS:000464093800015	30975991					
J	Bourbigot, S; Sarazin, J; Bensabath, T; Samyn, F; Jimenez, M				Bourbigot, Serge; Sarazin, Johan; Bensabath, Tsilla; Samyn, Fabienne; Jimenez, Maude			Intumescent polypropylene: Reaction to fire and mechanistic aspects	FIRE SAFETY JOURNAL					3rd European Symposium on fire Safety Sciences (ESFSS)	SEP 12-14, 2018	Nancy, FRANCE					The concept of intumescence was applied to make flame retarded polypropylene (PP). This paper examines two types of intumescence in PP based on expandable graphite (EG, physical expansion) and on modified ammonium polyphosphate (AP760, chemical expansion). Reaction to fire of PP containing EG and AP760 was first evaluated by cone calorimetry. The incorporation of intumescent additives at relatively low loading (10 wt%) in PP permits the reduction by 70% of peak of heat release rate (pHRR). The mode of action occurs via the formation of an expanded carbonaceous layer in all cases. The protective coating acts mainly as heat barrier in the case of the formulations containing AP760 or as heat dissipater with EG. The incorporation of small amount of EG in PP-AP760 modifies heat transfer in the coating creating a strong anisotropy. Upon expansion, graphite worms align normal to the surface increasing the transverse heat conductivity (lower efficiency of the heat barrier) and hence, decreasing the fire performance (decrease by only 30% of pHRR). Kinetic analysis was then performed to quantify the thermal stability of the intumescent systems. It reveals that the intumescent additives do not modify the reactional scheme of the PP thermal decomposition but they increase slightly the thermal stability of the intumescent systems. For all materials, the decomposition model follows a reactional scheme at two successive reactions. This model was determined in dynamic conditions (conditions of thermogravimetry with linear heating rates) but it is able to simulate the decomposition of the materials in isothermal conditions (excellent agreement between the simulated and experimental curves).					Bourbigot, Serge/0000-0003-1536-2015												0379-7112	1873-7226				APR	2019	105						261	269		10.1016/j.firesaf.2019.03.007							WOS:000468254800021						
J	Okyay, G; Samyn, F; Jimenez, M; Bourbigot, S				Okyay, Gizem; Samyn, Fabienne; Jimenez, Maude; Bourbigot, Serge			A Facile Technique to Extract the Cross-Sectional Structure of Brittle Porous Chars from Intumescent Coatings	POLYMERS												Intumescent coatings are part of passive fire protection systems. In case of fire, they expand under thermal stimuli and reduce heat transfer rates. Their expansion mechanisms are more or less recognized, but the fire testing data shall be interpreted as function of coating morphology. Expansion ratios are examined together with the inner structures of specimens submitted to fire. Bare cutting techniques damage the highly porous and fibrous specimens because they become very crumbly due to charring. So far, absorption contrasted X-ray computed microtomography (CT) was used as a non-destructive technique. Nevertheless, access to X-ray platforms can be relatively expensive and scarce for regular use. Also, it has some drawbacks for carbon rich specimens strongly adhering on steel substrates because it leads sometimes to noisy images and lost data due to resolution limits on specimens reaching ten of centimeters. Therefore, we propose an inexpensive and more accessible experimental approach to observe those specimens with minimized structural damage under visible lighting. To that end, charred specimens were casted into pigmented epoxy resin. After surface treatments, color contrasted cross-sections could be observed under optical digital microscopy thanks to high level of interconnectivity of pores. Subsequent image treatments confirmed that the structural integrity was kept when compared to previous CT data. The proposed method is practical, cheaper and more accessible for the quantitative assessment of inner structure of charred brittle specimens.					Okyay, Gizem/0000-0002-9661-6728; Bourbigot, Serge/0000-0003-1536-2015													2073-4360				APR	2019	11	4							640	10.3390/polym11040640							WOS:000467312900069	30970579					
J	Marques, TM; van Rumund, A; Oeckl, P; Kuiperij, HB; Esselink, RAJ; Bloem, BR; Otto, M; Verbeek, MM				Marques, Taina M.; van Rumund, Anouke; Oeckl, Patrick; Kuiperij, H. Bea; Esselink, Rianne A. J.; Bloem, Bastiaan R.; Otto, Markus; Verbeek, Marcel M.			Serum NFL discriminates Parkinson disease from atypical parkinsonisms	NEUROLOGY												Objective To investigate the diagnostic value of serum neurofilament light chain (NFL) in patients with clear signs of parkinsonism but whose specific diagnosis was yet uncertain. Methods Serum samples were collected from patients with clear signs of parkinsonism but with uncertain diagnosis at the inclusion. Clinical diagnoses of Parkinson disease (PD) and atypical parkinsonism disorders (APDs) were established after 3 years of follow-up and updated again after a maximum of 12 years in case longer follow-up data were available. Serum NFL was quantified by single molecule array in patients with PD (n = 55) and APD (n = 29, multiple system atrophy = 22, progressive supranuclear palsy = 7) and 53 nonneurologic controls. Results Serum NFL levels were elevated and differentiated the APD group (mean 23.8 +/- 10.3 ng/L) from PD (mean 10.4 +/- 4.9 ng/L) and controls (mean 11.5 +/- 6.5 ng/L, p < 0.0001) with accuracy levels up to 91% (sensitivity = 86% and specificity = 85%). Serum NFL strongly correlated with CSF NFL levels (r = 0.72, p < 0.0001) in all groups and with age in PD (r = 0.78, p < 0.0001) and controls (r = 0.66, p < 0.0001). In our cohort, the probability of having APD was 76% (positive predictive value) and of having PD 92% (negative predictive value). Conclusion Serum NFL levels are markedly elevated in APD compared to PD and discriminate APDs from PD with high accuracy. Serum NFL may be a useful clinical biomarker to identify APD, even at stages when clinical symptoms are not yet conclusive. Classification of evidence This study provides Class II evidence that serum NFL levels accurately discriminate APDs from PD.				Marques, Taina M/D-9702-2016; Verbeek, Marcel M/D-1971-2010; Otto, Markus/F-4304-2015; Kuiperij, Bea/A-4737-2013	Marques, Taina M/0000-0001-6098-2817; Verbeek, Marcel M/0000-0003-4635-7876; Otto, Markus/0000-0003-4273-4267; Kuiperij, Bea/0000-0002-0635-7428; Oeckl, Patrick/0000-0002-7652-7023												0028-3878	1526-632X				MAR 26	2019	92	13					E1479	E1486		10.1212/WNL.0000000000007179							WOS:000463260800021	30814322					
J	Li, KY; Hostikka, S				Li, Kaiyuan; Hostikka, Simo			Embedded flame heat flux method for simulation of quasi-steady state vertical flame spread	FIRE SAFETY JOURNAL												Flame spread has been an important but unsolved problem for decades as its numerical solution requires simultaneous accurate solutions in solid and gas phases. In the current study, a numerical model involving gas phase Large Eddy Simulation (LES) and comprehensive solid pyrolysis model was built as the first step of the research with a sufficient resolution for reproducing the flame spread rates in a set of upward flame spread experiments on birch rods. In the current conditions, the flame spread is dominated by the convective heat transfer and the predicted spread rates are thus sensitive to the heat transfer model. The convective and radiative heat fluxes during steady state were then extracted from the model results and used to improve the accuracy of coarse mesh simulations by embedding them as thermal boundary conditions for the solid phase. Three alternative techniques were investigated: Normalizing the heat flux profile with the length of the pyrolysis zone (fully coupled technique) resulted in accurate spread rates only if the initial pyrolysis zone was specified precisely and the gas phase resolution remained sufficiently fine. In the second, uncoupled technique, the length of the pyrolysis zone was fixed. Accurate steady state flame spread rates were then achieved regardless of the mesh resolution and the initial length of the pyrolysis zone. Finally, the most promising technique involved a normalized heat flux profile within the pyrolysis zone and a generalized heat flux function within the preheating zone. Correct spread rates were achieved with up to ten times increase in cell size regardless of the initial pyrolysis zone properties.				Hostikka, Simo/K-8622-2015	Hostikka, Simo/0000-0002-3581-1677												0379-7112	1873-7226				MAR	2019	104						117	129		10.1016/j.firesaf.2019.01.011							WOS:000464087500011						
J	Bourbigot, S; Sarazin, J; Samyn, F; Jimenez, M				Bourbigot, Serge; Sarazin, Johan; Samyn, Fabienne; Jimenez, Maude			Intumescent ethylene-vinyl acetate copolymer: Reaction to fire and mechanistic aspects	POLYMER DEGRADATION AND STABILITY												The concept of intumescence was applied to flame retard ethylene vinyl acetate copolymer (EVA). The paper examines two types of intumescence based on expandable graphite (EG, physical expansion) and on modified ammonium polyphosphate (AP760, chemical expansion). The incorporation of expandable graphite (EG) at relatively low loading (10wt%) in EVA permits the reduction up to 65% of peak of heat release rate (pHRR) measured by cone calorimetry. The mode of action occurs via the formation of an expanded carbonaceous layer acting mainly as heat barrier limiting heat and mass transfer as evidenced by the temperature measurement as a function of time during cone calorimetry. The incorporation of small amount of ZnCO3 in EVA-AP760 enhances strongly the performance: pHRR was not reduced using the sole AP760 while it is decreased by 54% when only 2 wt% of AP760 is substituted by ZnCO3. A strong synergistic effect was therefore observed. Solid state NMR of P-31 and C-13 on cone residues prepared at different characteristic times evidenced the mechanism involved is the reinforcement of the protective char by the formation of phosphate glass limiting the creation of cracks and increasing the char strength. (C) 2019 Elsevier Ltd. All rights reserved.					Bourbigot, Serge/0000-0003-1536-2015												0141-3910	1873-2321				MAR	2019	161						235	244		10.1016/j.polymdegradstab.2019.01.029							WOS:000462691200027						
J	Masaldan, S; Bush, AI; Devos, D; Rolland, AS; Moreau, C				Masaldan, Shashank; Bush, Ashley I.; Devos, David; Rolland, Anne Sophie; Moreau, Caroline			Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration	FREE RADICAL BIOLOGY AND MEDICINE												Perturbations in iron homeostasis and iron accumulation feature in several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). Proteins such as a-synuclein, tau and amyloid precursor protein that are pathologically associated with neurodegeneration are involved in molecular crosstalk with iron homeostatic proteins. Quantitative susceptibility mapping, an MRI based non-invasive technique, offers proximal evaluations of iron load in regions of the brain and powerfully predicts cognitive decline. Further, small molecules that target elevated iron have shown promise against PD and AD in preclinical studies and clinical trials. Despite these strong links between altered iron homeostasis and neurodegeneration the molecular biology to describe the association between enhanced iron levels and neuron death, synaptic impairment and cognitive decline is ill defined. In this review we discuss the current understanding of brain iron homeostasis and how it may be perturbed under pathological conditions. Further, we explore the ramifications of a novel cell death pathway called ferroptosis that has provided a fresh impetus to the "metal hypothesis" of neurodegeneration. While lipid peroxidation plays a central role in the execution of this cell death modality the removal of iron through chelation or genetic modifications appears to extinguish the ferroptotic pathway. Conversely, tissues that harbour elevated iron may be predisposed to ferroptotic damage. These emerging findings are of relevance to neurodegeneration where ferroptotic signalling may offer new targets to mitigate cell death and dysfunction.				Bush, Ashley I/A-1186-2007; Bush, Ashley/Y-2457-2019; Masaldan, Shashank/R-7591-2019; Devos, David/E-4059-2013	Bush, Ashley I/0000-0001-8259-9069; Bush, Ashley/0000-0001-8259-9069; Masaldan, Shashank/0000-0003-4960-4983; Devos, David/0000-0002-2417-799X												0891-5849	1873-4596				MAR	2019	133				SI		221	233		10.1016/j.freeradbiomed.2018.09.033							WOS:000457712300026	30266679					
J	Okyay, G; Naik, AD; Samyn, F; Jimenez, M; Bourbigot, S				Okyay, Gizem; Naik, Anil D.; Samyn, Fabienne; Jimenez, Maude; Bourbigot, Serge			Fractal conceptualization of intumescent fire barriers, toward simulations of virtual morphologies	SCIENTIFIC REPORTS												By limiting the heat spread during a fire hazard, intumescent coatings are important components of passive protection systems. They swell due to heat induced reactions of micro constituents and are transformed into carbonaceous porous-like media, known as intumescent chars. Their multiscale inner structures, key elements of performance, are costly to predict by recurrent and large scale fire testing while numerical simulations are challenging due to complex kinetics. Hence, we propose a novel approach using the fractal theory and the random nature of events to conceptualize the coating expansion. Experimental specimens were obtained from fire protective coatings exposed to bench scale hydrocarbon fire. Mass fractals were evidenced in the slices of 3D sample volumes reconstructed from X-ray microtomography. Consequently, geometrical building blocks were simulated by random walk, active walk, aggregation-like and site percolation: physical-chemical modes of action were inherent in the attribution of the randomness. It is a first demonstration to conceptualize different types of intumescent actions by a generalized approach with dimensionless parameters at multiscale, thus eliminating the simulation of complex kinetics to obtain a realistic morphology. Also, fractal results brought new evidence to former chemical analyses on fire test residues trying to explain the kinetics of expansion. Expected outcomes are to predict virtually the reaction of fire protective systems hence to speed-up the assessment of fire performance through computed properties of virtual volumes.					Okyay, Gizem/0000-0002-9661-6728												2045-2322					FEB 12	2019	9								1872	10.1038/s41598-019-38515-9							WOS:000458401500075	30755722					
J	Schonecker, S; Hell, F; Botzel, K; Wlasich, E; Ackl, N; Sussmair, C; Otto, M; Anderl-Straub, S; Ludolph, A; Kassubek, J; Huppertz, HJ; Diehl-Schmid, J; Riedl, L; Rossmeier, C; Fassbender, K; Lyros, E; Kornhuber, J; Oberstein, TJ; Fliessbach, K; Schneider, A; Schroeter, ML; Prudlo, J; Lauer, M; Jahn, H; Levin, J; Danek, A				Schoenecker, Sonja; Hell, Franz; Boetzel, Kai; Wlasich, Elisabeth; Ackl, Nibal; Suessmair, Christine; Otto, Markus; Anderl-Straub, Sarah; Ludolph, Albert; Kassubek, Jan; Huppertz, Hans-Juergen; Diehl-Schmid, Janine; Riedl, Lina; Rossmeier, Carola; Fassbender, Klaus; Lyros, Epameinondas; Kornhuber, Johannes; Oberstein, Timo Jan; Fliessbach, Klaus; Schneider, Anja; Schroeter, Matthias L.; Prudlo, Johannes; Lauer, Martin; Jahn, Holger; Levin, Johannes; Danek, Adrian		German FTLD Consortium	The applause sign in frontotemporal lobar degeneration and related conditions	JOURNAL OF NEUROLOGY												The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Recent research, however, has provided evidence for the occurrence of the applause sign in various conditions. The aim of this study was to determine the prevalence of the applause sign and correlate its presence with neuropsychological and MRI volumetry findings in frontotemporal lobar degeneration and related conditions. The applause sign was elicited with the three clap test (TCT), with a higher score indicating poorer performance. Data were recorded from 272 patients from the cohort of the German consortium for frontotemporal lobar degeneration (FTLDc): 111 with behavioral variant frontotemporal dementia (bvFTD), 98 with primary progressive aphasia (PPA), 30 with progressive supranuclear palsy Richardson's syndrome, 17 with corticobasal syndrome (CBS) and 16 with amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). For comparison, 29 healthy elderly control subjects (HC) were enrolled in the study. All subjects underwent detailed language and neuropsychological assessment. In a subset of 156 subjects, atlas-based volumetry was performed. The applause sign occurred in all patient groups (40% in PSP, 29.5% in CBS, 25% in ALS/FTD, 13.3% in PPA and 9.0% in bvFTD) but not in healthy controls. The prevalence was highest in PSP patients. It was significantly more common in PSP as compared to bvFTD, PPA and HC. The comparison between the other groups failed to show a significant difference regarding the occurrence of the applause sign. The applause sign was highly correlated to a number of neuropsychological findings, especially to measures of executive, visuospatial, and language function as well as measures of disease severity. TCT scores showed an inverse correlation with the volume of the ventral diencephalon and the pallidum. Furthermore the volume of the ventral diencephalon and pallidum were significantly smaller in patients displaying the applause sign. Our study confirms the occurrence of the applause sign in bvFTD, PSP and CBS and adds PPA and ALS/FTD to these conditions. Although still suggestive of PSP, clinically it must be interpreted with caution. From the correlation with various cognitive measures we suggest the applause sign to be indicative of disease severity. Furthermore we suggest that the applause sign represents dysfunction of the pallidum and the subthalamic nucleus, structures which are known to play important roles in response inhibition.				Levin, Johannes/E-4052-2010; Kassubek, Jan/F-2774-2015	Levin, Johannes/0000-0001-5092-4306; Kassubek, Jan/0000-0002-7106-9270; Huppertz, Hans-Jurgen/0000-0003-3856-9094; Diehl-Schmid, Janine/0000-0002-7745-1382; Fassbender, Klaus/0000-0003-3596-868X												0340-5354	1432-1459				FEB	2019	266	2					330	338		10.1007/s00415-018-9134-y							WOS:000458151200006	30506397					
J	Oeckl, P; Weydt, P; Steinacker, P; Anderl-Straub, S; Nordin, F; Volk, AE; Diehl-Schmid, J; Andersen, PM; Kornhuber, J; Danek, A; Fassbender, K; Fliessbach, K; Jahn, H; Lauer, M; Muller, K; Knehr, A; Prudlo, J; Schneider, A; Thal, DR; Yilmazer-Hanke, D; Weishaupt, JH; Ludolph, AC; Otto, M				Oeckl, Patrick; Weydt, Patrick; Steinacker, Petra; Anderl-Straub, Sarah; Nordin, Frida; Volk, Alexander E.; Diehl-Schmid, Janine; Andersen, Peter M.; Kornhuber, Johannes; Danek, Adrian; Fassbender, Klaus; Fliessbach, Klaus; Jahn, Holger; Lauer, Martin; Mueller, Kathrin; Knehr, Antje; Prudlo, Johannes; Schneider, Anja; Thal, Dietmar R.; Yilmazer-Hanke, Deniz; Weishaupt, Jochen H.; Ludolph, Albert C.; Otto, Markus		German Consortium Frontotemporal L	Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase	JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY												Objective To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers. Methods The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA. Results CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05). Conclusion Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.				Thal, Dietmar/Y-8405-2019; Jahn, Holger/A-9255-2008; Danek, Adrian/G-7339-2011; Otto, Markus/F-4304-2015	Thal, Dietmar/0000-0002-1036-1075; Jahn, Holger/0000-0003-3607-7651; Danek, Adrian/0000-0001-8857-5383; Otto, Markus/0000-0003-4273-4267; Oeckl, Patrick/0000-0002-7652-7023; Fassbender, Klaus/0000-0003-3596-868X; Diehl-Schmid, Janine/0000-0002-7745-1382												0022-3050	1468-330X				JAN	2019	90	1					4	10		10.1136/jnnp-2018-318868							WOS:000459181800004	30224549					
J	Bilyy, R; Paryzhak, S; Turcheniuk, K; Dumych, T; Barras, A; Boukherroub, R; Wang, FJ; Yushin, G; Szunerits, S				Bilyy, Rostyslav; Paryzhak, Solomiya; Turcheniuk, Kostiantyn; Dumych, Tetiana; Barras, Alexandre; Boukherroub, Rabah; Wang, Fujia; Yushin, Gleb; Szunerits, Sabine			Aluminum oxide nanowires as safe and effective adjuvants for next-generation vaccines	MATERIALS TODAY												Improving efficiency of an adjuvant, material that enhances the body's immune response to an antigen, has become vital for the development of safer, cheaper, and more effective next-generation vaccines. Commercial vaccines typically use aluminum salt-based adjuvant particles, most commonly aluminum oxyhydroxide (AlOOH) and aluminum hydroxide (Al(OH)(3)) based, often referred to as "alum". Despite their broad use, their adjuvant properties are rather moderate. This is even worse in the case of aluminum oxide (Al2O3)-based adjuvant. While being more robust and less cytotoxic, Al2O3 is a significantly less effective adjuvant than above-mentioned Al compounds and is consequently not commonly used. Here, we report on the remarkably enhanced adjuvant properties of Al2O3 when produced in the form of nanowires (NWs). Based on recent advances in understanding neutrophil activation by inert nanoscaffolds, we have created ultra-long Al2O3 NWs with a high aspect ratio of similar to 1000. These NWs showed strong humoral immune response with no damaging effect on the microvasculature. Since only the change of shape of Al adjuvants is responsible for the excellent adjuvant properties, our finding holds great promise for rapid implementation as safer and more effective adjuvant alternative for human vaccines. The mechanism behind human blood-derived neutrophil activation with Al2O3 NWs was found to be sequestering of Al2O3 NWs by neutrophils via formation of neutrophil extracellular traps (NETs).				Yushin, Gleb/B-4529-2013; Bilyy, Rostyslav/A-9777-2010; Paryzhak, Solomiya/G-4819-2019	Yushin, Gleb/0000-0002-3274-9265; Bilyy, Rostyslav/0000-0002-2344-1349; Paryzhak, Solomiya/0000-0002-1491-3711; Szunerits, Sabine/0000-0002-1567-4943												1369-7021	1873-4103				JAN-FEB	2019	22						58	66		10.1016/j.mattod.2018.10.034							WOS:000458525700026						
J	Oeckl, P; Halbgebauer, S; Anderl-Straub, S; Steinacker, P; Huss, AM; Neugebauer, H; von Arnim, CAF; Diehl-Schmid, J; Grimmer, T; Kornhuber, J; Lewczuk, P; Danek, A; Ludolph, AC; Otto, M				Oeckl, Patrick; Halbgebauer, Steffen; Anderl-Straub, Sarah; Steinacker, Petra; Huss, Andre M.; Neugebauer, Hermann; von Arnim, Christine A. F.; Diehl-Schmid, Janine; Grimmer, Timo; Kornhuber, Johannes; Lewczuk, Piotr; Danek, Adrian; Ludolph, Albert C.; Otto, Markus		German Consortium Frontotemporal L	Glial Fibrillary Acidic Protein in Serum is Increased in Alzheimer's Disease and Correlates with Cognitive Impairment	JOURNAL OF ALZHEIMERS DISEASE												Reliable blood biomarkers for Alzheimer's disease (AD) are missing. We measured astroglial GFAP in patients with AD (n = 28), frontotemporal dementia (bvFTD, n = 35), Parkinson's disease (n = 11), Lewy body dementias (n = 19), and controls (n = 34). Serum GFAP was increased in AD (p < 0.001) and DLB/PDD (p < 0.01), and cerebrospinal fluid GFAP was increased in all neurodegenerative diseases (p < 0.001). Serum GFAP correlated with the Mini-Mental State Examination score (r = -0.42, p < 0.001) and might be a follow-up marker in clinical trials. Sensitivity and specificity of serum GFAP for AD versus bvFTD was 89% and 79% and might be the first blood biomarker in the differential diagnosis of AD and bvFTD.				Danek, Adrian/G-7339-2011; Neugebauer, Hermann/AAD-8309-2019; Otto, Markus/F-4304-2015	Danek, Adrian/0000-0001-8857-5383; Neugebauer, Hermann/0000-0003-3759-356X; Otto, Markus/0000-0003-4273-4267; Oeckl, Patrick/0000-0002-7652-7023; Diehl-Schmid, Janine/0000-0002-7745-1382												1387-2877	1875-8908					2019	67	2					481	488		10.3233/JAD-180325							WOS:000457779300004	30594925					
J	Altinbasak, I; Jijie, R; Barras, A; Golba, B; Sanyal, R; Bouckaert, J; Drider, D; Bilyy, R; Dumych, T; Paryzhak, S; Vovk, V; Boukherroub, R; Sanyal, A; Szunerits, S				Altinbasak, Ismail; Jijie, Roxana; Barras, Alexandre; Golba, Bianka; Sanyal, Rana; Bouckaert, Julie; Drider, Djamel; Bilyy, Rostyslav; Dumych, Tetiana; Paryzhak, Solomiya; Vovk, Volodymyr; Boukherroub, Rabah; Sanyal, Amitav; Szunerits, Sabine			Reduced Graphene-Oxide-Embedded Polymeric Nanofiber Mats: An "On-Demand" Photothermally Triggered Antibiotic Release Platform	ACS APPLIED MATERIALS & INTERFACES												The steady increase of antimicrobial resistance of different pathogens requires the development of alternative treatment strategies next to the oral delivery of antibiotics. A photothermally activated platform based on reduced graphene oxide (rGO)-embedded polymeric nanofiber mats for on-demand release of antibiotics upon irradiation in the near-infrared is fabricated. Cross-linked hydrophilic nanofibers, obtained by electrospinning a mixture of poly(acrylic acid) (PAA) and rGO, show excellent stability in aqueous media. Importantly, these PAA@rGO nanofiber mats exhibit controlled photothermal heating upon irradiation at 980 nm. Nanofiber mats are efficiently loaded with antibiotics through simple immersion into corresponding antibiotics solutions. Whereas passive diffusion based release at room temperature is extremely low, photothermal activation results in increased release within few minutes, with release rates tunable through power density of the applied irradiation. The large difference over passive and active release, as regulation of the dosage of the antibiotics, as evidenced by the inhibition of planktonic bacteria growth. Treatment of superficial skin infections with the antibiotic-loaded nanofiber mats shows efficient wound healing of the infected site. Facile fabrication and implementation of these photothermally active nanofiber mats makes this novel platform adaptable for on-demand delivery of various therapeutic agents.				Bilyy, Rostyslav/A-9777-2010	Bilyy, Rostyslav/0000-0002-2344-1349; Vovk, Volodymyr/0000-0002-8411-267X; Bouckaert, Julie/0000-0001-8112-1442												1944-8244					DEC 5	2018	10	48					41098	41106		10.1021/acsami.8b14784							WOS:000452694100017	30376295					
J	Szunerits, S; Boukherroub, R				Szunerits, Sabine; Boukherroub, Rabah			Graphene-based bioelectrochemistry and bioelectronics: A concept for the future?	CURRENT OPINION IN ELECTROCHEMISTRY												Situated at the interface of materials science, chemistry and the life sciences, graphene-based electronics and electrochemistry offer a broad palette of opportunities for researchers and clinicians for targeted theranostics as outlined in this article.					Szunerits, Sabine/0000-0002-1567-4943												2451-9103					DEC	2018	12						141	147		10.1016/j.coelec.2018.03.028							WOS:000453329900019						
J	Berthier, A; Vinod, M; Porez, G; Steenackers, A; Alexandre, J; Yamakawa, N; Gheeraert, C; Ploton, M; Marechal, X; Dubois-Chevalier, J; Hovasse, A; Schaeffer-Reiss, C; Cianferani, S; Rolando, C; Bray, F; Duez, H; Eeckhoute, J; Lefebvre, T; Staels, B; Lefebvre, P				Berthier, Alexandre; Vinod, Manjula; Porez, Geoffrey; Steenackers, Agata; Alexandre, Jeremy; Yamakawa, Nao; Gheeraert, Celine; Ploton, Maheul; Marechal, Xavier; Dubois-Chevalier, Julie; Hovasse, Agnes; Schaeffer-Reiss, Christine; Cianferani, Sarah; Rolando, Christian; Bray, Fabrice; Duez, Helene; Eeckhoute, Jerome; Lefebvre, Tony; Staels, Bart; Lefebvre, Philippe			Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERB alpha complex	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA												The nuclear receptor REV-ERB alpha integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERB alpha-interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT activity in the nucleus, REV-ERB alpha cyclically increased O-GlcNAcylation of multiple cytoplasmic and nuclear proteins as a function of its rhythmically regulated expression, while REV-ERB alpha ligands mostly affected cytoplasmic OGT activity. We illustrate this finding by showing that REV-ERB alpha controls OGT-dependent activities of the cytoplasmic protein kinase AKT, an essential relay in insulin signaling, and of ten-of-eleven translocation (TET) enzymes in the nucleus. AKT phosphorylation was inversely correlated to REV-ERB alpha expression. REV-ERB alpha enhanced TET activity and DNA hydroxymethylated cytosine (5hmC) levels in the vicinity of REV-ERB alpha genomic binding sites. As an example, we show that the REV-ERB alpha/OGT complex modulates SREBP-1c gene expression throughout the fasting/feeding periods by first repressing AKT phosphorylation and by epigenomically priming the Srebf1 promoter for a further rapid response to insulin. Conclusion: REV-ERB alpha regulates cytoplasmic and nuclear OGT-controlled processes that integrate at the hepatic SREBF1 locus to control basal and insulin-induced expression of the temporally and nutritionally regulated lipogenic SREBP-1c transcript.				Duez, Helene/AAC-3217-2019; Berthier, Alexandre/O-6566-2019; Staels, Bart/N-9497-2016	Duez, Helene/0000-0002-4130-7987; Berthier, Alexandre/0000-0003-4153-4810; Staels, Bart/0000-0002-3784-1503; PLOTON, Maheul/0000-0002-1569-0070; Bray, Fabrice/0000-0002-4723-8206												0027-8424					NOV 20	2018	115	47					E11033	E11042		10.1073/pnas.1805397115							WOS:000450642800008	30397120					
J	Ploton, M; Mazuy, C; Gheeraert, C; Dubois, V; Berthier, A; Dubois-Chevalier, J; Marechal, X; Bantubungi, K; Diemer, H; Cianferani, S; Strub, JM; Helleboid-Chapman, A; Eeckhoute, J; Staels, B; Lefebvre, P				Ploton, Maheul; Mazuy, Claire; Gheeraert, Celine; Dubois, Vanessa; Berthier, Alexandre; Dubois-Chevalier, Julie; Marechal, Xavier; Bantubungi, Kadiombo; Diemer, Helene; Cianferani, Sarah; Strub, Jean-Marc; Helleboid-Chapman, Audrey; Eeckhoute, Jerome; Staels, Bart; Lefebvre, Philippe			The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis	JOURNAL OF HEPATOLOGY												Background & Aims: Embedded into a complex signaling network that coordinates glucose uptake, usage and production, the nuclear bile acid receptor FXR is expressed in several glucose-processing organs including the liver. Hepatic gluconeogenesis is controlled through allosteric regulation of gluconeogenic enzymes and by glucagon/cAMP-dependent transcriptional regulatory pathways. We aimed to elucidate the role of FXR in the regulation of fasting hepatic gluconeogenesis. Methods: The role of FXR in hepatic gluconeogenesis was assessed in vivo and in mouse primary hepatocytes. Gene expression patterns in response to glucagon and FXR agonists were characterized by quantitative reverse transcription PCR and microarray analysis. FXR phosphorylation by protein kinase A was determined by mass spectrometry. The interaction of FOXA2 with FXR was identified by cistromic approaches and in vitro protein-protein interaction assays. The functional impact of the crosstalk between FXR, the PKA and FOXA2 signaling pathways was assessed by site-directed mutagenesis, transactivation assays and restoration of FXR expression in FXR-deficient hepatocytes in which gene expression and glucose production were assessed. Results: FXR positively regulates hepatic glucose production through two regulatory arms, the first one involving protein kinase A-mediated phosphorylation of FXR, which allowed for the synergistic activation of gluconeogenic genes by glucagon, agonist-activated FXR and CREB. The second arm involves the inhibition of FXR's ability to induce the anti-gluconeogenic nuclear receptor SHP by the glucagon-activated FOXA2 transcription factor, which physically interacts with FXR. Additionally, knockdown of Foxa2 did not alter glucagon-induced and FXR agonist enhanced expression of gluconeogenic genes, suggesting that the PKA and FOXA2 pathways regulate distinct subsets of FXR responsive genes. Conclusions: Thus, hepatic glucose production is regulated during physiological fasting by FXR, which integrates the glucagon/cAMP signal and the FOXA2 signal, by being post-translationally modified, and by engaging in protein-protein interactions, respectively. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V.				Berthier, Alexandre/O-6566-2019; Lefebvre, Philippe/F-2685-2010; Marechal, Xavier/R-5762-2018; Staels, Bart/N-9497-2016	Berthier, Alexandre/0000-0003-4153-4810; Lefebvre, Philippe/0000-0002-9366-5129; Marechal, Xavier/0000-0001-6399-7811; Staels, Bart/0000-0002-3784-1503; Dubois, Vanessa/0000-0001-8894-2980; PLOTON, Maheul/0000-0002-1569-0070; bantubungi, kadiombo/0000-0002-6152-5623; Dubois-Chevalier, Julie/0000-0003-0471-752X												0168-8278	1600-0641				NOV	2018	69	5					1099	1109		10.1016/j.jhep.2018.06.022							WOS:000447267500015	29981427					
J	Dumych, T; Bridot, C; Gouin, SG; Lensink, MF; Paryzhak, S; Szunerits, S; Blossey, R; Bilyy, R; Bouckaert, J; Krammer, EM				Dumych, Tetiana; Bridot, Clarisse; Gouin, Sebastien G.; Lensink, Marc F.; Paryzhak, Solomiya; Szunerits, Sabine; Blossey, Ralf; Bilyy, Rostyslav; Bouckaert, Julie; Krammer, Eva-Maria			A Novel Integrated Way for Deciphering the Glycan Code for the FimH Lectin	MOLECULES												The fimbrial lectin FimH from uro- and enteropathogenic Escherichia coli binds with nanomolar affinity to oligomannose glycans exposing Man alpha 1,3Man dimannosides at their non-reducing end, but only with micromolar affinities to Man alpha 1,2Man dimannosides. These two dimannoses play a significantly distinct role in infection by E. coli. Man alpha 1,2Man has been described early on as shielding the (Man alpha 1,3Man) glycan that is more relevant to strong bacterial adhesion and invasion. We quantified the binding of the two dimannoses (Man alpha 1,2Man and Man alpha 1,3Man to FimH using ELLSA and isothermal microcalorimetry and calculated probabilities of binding modes using molecular dynamics simulations. Our experimentally and computationally determined binding energies confirm a higher affinity of FimH towards the dimannose Man alpha 1,3Man. Man alpha 1,2Man displays a much lower binding enthalpy combined with a high entropic gain. Most remarkably, our molecular dynamics simulations indicate that Man alpha 1,2Man cannot easily take its major conformer from water into the FimH binding site and that FimH is interacting with two very different conformers of Man alpha 1,2Man that occupy 42% and 28% respectively of conformational space. The finding that Man alpha 1,2Man binding to FimH is unstable agrees with the earlier suggestion that E. coli may use the Man alpha 1,2Man epitope for transient tethering along cell surfaces in order to enhance dispersion of the infection.				Lensink, Marc F/A-1678-2008; Bilyy, Rostyslav/A-9777-2010; Krammer, Eva-Maria/H-2543-2013; Dumych, Tetiana/H-9450-2018	Lensink, Marc F/0000-0003-3957-9470; Bilyy, Rostyslav/0000-0002-2344-1349; Krammer, Eva-Maria/0000-0002-4821-2550; Dumych, Tetiana/0000-0002-8489-5600; gouin, sebastien/0000-0002-0985-1165; Blossey, Ralf/0000-0002-4823-7037; Bouckaert, Julie/0000-0001-8112-1442												1420-3049					NOV	2018	23	11							2794	10.3390/molecules23112794							WOS:000451641900066	30373288					
J	Barras, A; Skandrani, N; Pisfil, MG; Paryzhak, S; Dumych, T; Haustrate, A; Heliot, L; Gharbi, T; Boulahdour, H; Lehen'kyi, V; Bilyy, R; Szunerits, S; Bidaux, G; Boukherroub, R				Barras, Alexandre; Skandrani, Nadia; Pisfil, Mariano Gonzalez; Paryzhak, Solomiya; Dumych, Tetiana; Haustrate, Aurelien; Heliot, Laurent; Gharbi, Tijani; Boulahdour, Hatem; Lehen'kyi, V'yacheslav; Bilyy, Rostyslav; Szunerits, Sabine; Bidaux, Gabriel; Boukherroub, Rabah			Improved photodynamic effect through encapsulation of two photosensitizers in lipid nanocapsules	JOURNAL OF MATERIALS CHEMISTRY B												Photodynamic therapy (PDT) has developed into a new clinical and non-invasive treatment for cancer over the past 30 years. By the combination of three non-toxic partners, i.e. a photosensitizer (PS), molecular oxygen (O-2) and light, cytotoxic reactive oxygen species (ROS) are locally produced leading to irreversible vascular and cellular damage. In the present study, we report for the first time that the combination of two photosensitizers (2 PSs: Protoporphyrin IX, PpIX and Hypericin, Hy) loaded in the same lipid nanocapsules (LNCs) leads to enhanced photodynamic therapy efficiency when compared with previously reported systems. The 2 PS-loaded LNCs are shown to increase the in vitro phototoxicity at the nanomolar range (IC50 = 274 and 278 nM on HeLa and MDA-MB-231 cell lines, respectively), whereas the corresponding single PS-loaded LNCs at the same concentration exhibit a phototoxicity two times lower. Intracellular localization in HeLa cells indicates a subcellular asymmetry of PpIX and Hy, in the plasma, ER membranes and round internal structures. The biodistribution of LNCs was studied upon different routes of injection into Swiss nude mice; based on the obtained data, LNCs were injected intratumorally and used to slow the growth of xenograft tumors in mice. The results obtained in this study suggest that the combination of two or more PSs may be a promising strategy to improve the efficacy of conventional photodynamic therapy as well as to reduce dark toxicity.				Paryzhak, Solomiya/G-4819-2019; LAB, Carmen/X-8895-2019; Carmen, Team3/Y-7384-2019; Dumych, Tetiana/H-9450-2018; Bidaux, Gabriel/F-1294-2016	Paryzhak, Solomiya/0000-0002-1491-3711; LAB, Carmen/0000-0002-5935-3236; Carmen, Team3/0000-0002-3614-0924; LEHEN'KYI, V'yacheslav/0000-0003-0806-8766; Dumych, Tetiana/0000-0002-8489-5600; Bidaux, Gabriel/0000-0002-6162-3223												2050-750X	2050-7518				OCT 7	2018	6	37					5949	5963		10.1039/c8tb01759j							WOS:000447949600012						
J	Jijie, R; Barras, A; Bouckaert, J; Dumitrascu, N; Szunerits, S; Boukherroub, R				Jijie, Roxana; Barras, Alexandre; Bouckaert, Julie; Dumitrascu, Nicoleta; Szunerits, Sabine; Boukherroub, Rabah			Enhanced antibacterial activity of carbon dots functionalized with ampicillin combined with visible light triggered photodynamic effects	COLLOIDS AND SURFACES B-BIOINTERFACES												In the last years, carbon-based nanomaterials have attracted considerable attention in a wide range of fields, particularly in biomedicine, owing to their remarkable photo-physical and chemical properties. In this study, we demonstrate that amine-terminated carbon dots (CDs-NH2) functionalized with ampicillin (AMP) offer a new perspective for antibacterial treatment. The amine-functionalized carbon dots were used as a carrier for immobilization and delivery of ampicillin (CDs-AMP) and as a visible light-triggered antibacterial material. Additionally, AMP immobilization on the CDs-NH2 surface improves its stability in solution as compared to free AMP. The AMP conjugated CDs platform combines the antibacterial function of AMP and conserves the intrinsic theranostic properties of CDs-NH2. Therefore, the AMP immobilized onto CDs-NH2 surface together with the generation of moderate quantities of reactive oxygen species under visible light illumination are very effective to inactivate the growth of Escherichia coli.																	0927-7765	1873-4367				OCT 1	2018	170						347	354		10.1016/j.colsurfb.2018.06.040							WOS:000445989400041	29940501					
J	Bougarne, N; Weyers, B; Desmet, SJ; Deckers, J; Ray, DW; Staels, B; De Bosscher, K				Bougarne, Nadia; Weyers, Basiel; Desmet, Sofie J.; Deckers, Julie; Ray, David W.; Staels, Bart; De Bosscher, Karolien			Molecular Actions of PPAR alpha in Lipid Metabolism and Inflammation	ENDOCRINE REVIEWS												Peroxisome proliferator-activated receptor a (PPAR alpha) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPAR alpha also exhibits marked anti-inflammatory capacities. The first-generation PPAR alpha agonists, the fibrates, have however been hampered by drug-drug interaction issues, statin drop-in, and ill-designed cardiovascular intervention trials. Notwithstanding, understanding the molecular mechanisms by which PPAR alpha works will enable control of its activities as a drug target for metabolic diseases with an underlying inflammatory component. Given its role in reshaping the immune system, the full potential of this nuclear receptor subtype as a versatile drug target with high plasticity becomes increasingly clear, and a novel generation of agonists may pave the way for novel fields of applications.				Staels, Bart/N-9497-2016	Staels, Bart/0000-0002-3784-1503; De Bosscher, Karolien/0000-0001-5059-9718; Ray, David/0000-0002-4739-6773												0163-769X	1945-7189				OCT	2018	39	5					760	802		10.1210/er.2018-00064							WOS:000448057900010	30020428					
J	Bobowski-Gerard, M; Zummo, FP; Staels, B; Lefebvre, P; Eeckhoute, J				Bobowski-Gerard, Marie; Zummo, Francesco Paolo; Staels, Bart; Lefebvre, Philippe; Eeckhoute, Jerome			Retinoids Issued from Hepatic Stellate Cell Lipid Droplet Loss as Potential Signaling Molecules Orchestrating a Multicellular Liver Injury Response	CELLS												Hepatic stellate cells (HSCs) serve as the main body storage compartment for vitamin A through retinyl ester (RE)-filled lipid droplets (LDs). Upon liver injury, HSCs adopt a myofibroblastic phenotype characterized by an elevated expression of extracellular matrix proteins and a concomitant loss of LDs. On the one hand, LD breakdown has been suggested to provide the energy required for HSC activation into myofibroblast-like cells. On the other hand, this process could mitigate HSC activation following the transformation of released REs into retinoic acids (RAs), ligands for nuclear receptors exerting antifibrotic transcriptional regulatory activities in HSCs. Importantly, RAs may also constitute a means for HSCs to orchestrate the liver response to injury by triggering transcriptional effects in multiple additional surrounding liver cell populations. We envision that new approaches, such as single-cell technologies, will allow to better define how RAs are issued from LD loss in HSCs exert a multicellular control of the liver (patho)physiology.				Staels, Bart/N-9497-2016; Lefebvre, Philippe/F-2685-2010	Staels, Bart/0000-0002-3784-1503; Lefebvre, Philippe/0000-0002-9366-5129; Zummo, Francesco Paolo/0000-0001-5923-1784; Bobowski-Gerard, Marie/0000-0002-0915-0799; Eeckhoute, Jerome/0000-0002-7222-9264													2073-4409				SEP	2018	7	9							137	10.3390/cells7090137							WOS:000448332400024	30217095					
J	Geoffroy, L; Samyn, F; Jimenez, M; Bourbigot, S				Geoffroy, Laura; Samyn, Fabienne; Jimenez, Maude; Bourbigot, Serge			Intumescent Polymer Metal Laminates for Fire Protection	POLYMERS												Intumescent paints are applied on materials to protect them against fire, but the development of novel chemistries has reached some limits. Recently, the concept of "Polymer Metal Laminates," consisting of alternating thin aluminum foils and thin epoxy resin layers has been proven efficient against fire, due to the delamination between layers during burning. In this paper, both concepts were considered to design "Intumescent Polymer Metal Laminates" (IPML), i.e., successive thin layers of aluminum foils and intumescent coatings. Three different intumescent coatings were selected to prepare ten-plies IPML glued onto steel substrates. The IPMLs were characterized using optical microscopy, and their efficiency towards fire was evaluated using a burn-through test. Thermal profiles obtained were compared to those obtained for a monolayer of intumescent paint. For two of three coatings, the use of IPML revealed a clear improvement at the beginning of the test, with the slopes of the curves being dramatically decreased. Characterizations (expansion measurements, microscopic analyses, in situ temperature, and thermal measurements) were carried out on the different samples. It is suggested that the polymer metal laminates (PML) design, delays the carbonization of the residue. This work highlighted that design is as important as the chemistry of the formulation, to obtain an effective fire barrier.					GEOFFROY, Laura/0000-0002-0834-2000; Bourbigot, Serge/0000-0003-1536-2015												2073-4360					SEP	2018	10	9							995	10.3390/polym10090995							WOS:000449988800064	30960919					
J	Pham, MH; Warmerdam, E; Elshehabi, M; Schlenstedt, C; Bergeest, LM; Heller, M; Haertner, L; Ferreira, JJ; Berg, D; Schmidt, G; Hansen, C; Maetzler, W				Pham, Minh H.; Warmerdam, Elke; Elshehabi, Morad; Schlenstedt, Christian; Bergeest, Lu-Marie; Heller, Maren; Haertner, Linda; Ferreira, Joaquim J.; Berg, Daniela; Schmidt, Gerhard; Hansen, Clint; Maetzler, Walter			Validation of a Lower Back "Wearable"-Based Sit-to-Stand and Stand-to-Sit Algorithm for Patients With Parkinson's Disease and Older Adults in a Home-Like Environment	FRONTIERS IN NEUROLOGY												Introduction: Impaired sit-to-stand and stand-to-sit movements (postural transitions, PTs) in patients with Parkinson's disease (PD) and older adults (OA) are associated with risk of falling and reduced quality of life. Inertial measurement units (IMUs, also called "wearables") are powerful tools to monitor PT kinematics. The purpose of this study was to develop and validate an algorithm, based on a single IMU positioned at the lower back, for PT detection and description in the above-mentioned groups in a home-like environment. Methods: Four PD patients (two with dyskinesia) and one OA served as algorithm training group, and 21 PD patients (16 without and 5 with dyskinesia) and 11 OA served as test group. All wore an IMU on the lower back and were videotaped while performing everyday activities for 90-180 min in a non-standardized home-like environment. Accelerometer and gyroscope signals were analyzed using discrete wavelet transformation (DWT), a six degrees-of-freedom (DOF) fusion algorithm and vertical displacement estimation. Results: From the test group, 1,001 PTs, defined by video reference, were analyzed. The accuracy of the algorithm for the detection of PTs against video observation was 82% for PD patients without dyskinesia, 47% for PD patients with dyskinesia and 85% for OA. The overall accuracy of the PT direction detection was comparable across groups and yielded 98%. Mean PT duration values were 1.96 s for PD patients and 1.74 s for OA based on the algorithm (p < 0.001) and 1.77 s for PD patients and 1.51 s for OA based on clinical observation (p < 0.001). Conclusion: Validation of the PT detection algorithm in a home-like environment shows acceptable accuracy against the video reference in PD patients without dyskinesia and controls. Current limitations are the PT detection in PD patients with dyskinesia and the use of video observation as the video reference. Potential reasons are discussed.				Maetzler, Walter/A-6796-2011; Schlenstedt, Christian/I-3443-2019; Hansen, Clint/J-4961-2019; Deuschl, Gunther/A-7986-2010; Berg, Daniela D/A-8728-2019	Maetzler, Walter/0000-0002-5945-4694; Schlenstedt, Christian/0000-0002-3838-6848; Hansen, Clint/0000-0003-4813-3868; Berg, Daniela D/0000-0001-5796-5442												1664-2295					AUG 10	2018	9								652	10.3389/fneur.2018.00652							WOS:000441320600001	30158894					
J	Liu, J; Xiong, RH; Brans, T; Lippens, S; Parthoens, E; Zanacchi, FC; Magrassi, R; Singh, SK; Kurungot, S; Szunerits, S; Bove, H; Ameloot, M; Fraire, JC; Teirlinck, E; Samal, SK; De Rycke, R; Houthaeve, G; De Smedt, SC; Boukherroub, R; Braeckmans, K				Liu, Jing; Xiong, Ranhua; Brans, Toon; Lippens, Saskia; Parthoens, Eef; Zanacchi, Francesca Cella; Magrassi, Raffaella; Singh, Santosh K.; Kurungot, Sreekumar; Szunerits, Sabine; Bove, Hannelore; Ameloot, Marcel; Fraire, Juan C.; Teirlinck, Eline; Samal, Sangram Keshari; De Rycke, Riet; Houthaeve, Gaelle; De Smedt, Stefaan C.; Boukherroub, Rabah; Braeckmans, Kevin			Repeated photoporation with graphene quantum dots enables homogeneous labeling of live cells with extrinsic markers for fluorescence microscopy	LIGHT-SCIENCE & APPLICATIONS												In the replacement of genetic probes, there is increasing interest in labeling living cells with high-quality extrinsic labels, which avoid over-expression artifacts and are available in a wide spectral range. This calls for a broadly applicable technology that can deliver such labels unambiguously to the cytosol of living cells. Here, we demonstrate that nanoparticle-sensitized photoporation can be used to this end as an emerging intracellular delivery technique. We replace the traditionally used gold nanoparticles with graphene nanoparticles as photothermal sensitizers to permeabilize the cell membrane upon laser irradiation. We demonstrate that the enhanced thermal stability of graphene quantum dots allows the formation of multiple vapor nanobubbles upon irradiation with short laser pulses, allowing the delivery of a variety of extrinsic cell labels efficiently and homogeneously into live cells. We demonstrate high-quality time-lapse imaging with confocal, total internal reflection fluorescence (TIRF), and Airyscan super-resolution microscopy. As the entire procedure is readily compatible with fluorescence (super resolution) microscopy, photoporation with graphene quantum dots has the potential to become the long-awaited generic platform for controlled intracellular delivery of fluorescent labels for live-cell imaging.				Samal, Sangram K/H-5442-2013													2047-7538					AUG 8	2018	7								47	10.1038/s41377-018-0048-3							WOS:000441267100001						
J	Mayeuf-Louchart, A; Hardy, D; Thorel, Q; Roux, P; Gueniot, L; Briand, D; Mazeraud, A; Bougle, A; Shorte, SL; Staels, B; Chretien, F; Duez, H; Danckaert, A				Mayeuf-Louchart, Alicia; Hardy, David; Thorel, Quentin; Roux, Pascal; Gueniot, Lorna; Briand, David; Mazeraud, Aurelien; Bougle, Adrien; Shorte, Spencer L.; Staels, Bart; Chretien, Fabrice; Duez, Helene; Danckaert, Anne			MuscleJ: a high-content analysis method to study skeletal muscle with a new Fiji tool	SKELETAL MUSCLE												Background: Skeletal muscle has the capacity to adapt to environmental changes and regenerate upon injury. To study these processes, most experimental methods use quantification of parameters obtained from images of immunostained skeletal muscle. Muscle cross-sectional area, fiber typing, localization of nuclei within the muscle fiber, the number of vessels, and fiber-associated stem cells are used to assess muscle physiology. Manual quantification of these parameters is time consuming and only poorly reproducible. While current state-of-the-art software tools are unable to analyze all these parameters simultaneously, we have developed MuscleJ, a new bioinformatics tool to do so. Methods: Running on the popular open source Fiji software platform, MuscleJ simultaneously analyzes parameters from immunofluorescent staining, imaged by different acquisition systems in a completely automated manner. Results: After segmentation of muscle fibers, up to three other channels can be analyzed simultaneously. Dialog boxes make MuscleJ easy-to-use for biologists. In addition, we have implemented color in situ cartographies of results, allowing the user to directly visualize results on reconstituted muscle sections. Conclusion: We report here that MuscleJ results were comparable to manual observations made by five experts. MuscleJ markedly enhances statistical analysis by allowing reliable comparison of skeletal muscle physiology-pathology results obtained from different laboratories using different acquisition systems. Providing fast robust multi-parameter analyses of skeletal muscle physiology-pathology, MuscleJ is available as a free tool for the skeletal muscle community.				Duez, Helene/AAC-3217-2019; Staels, Bart/N-9497-2016; Mayeuf-Louchart, Alicia/AAC-5102-2019; Duez, Helene/M-7609-2017	Duez, Helene/0000-0002-4130-7987; Staels, Bart/0000-0002-3784-1503; Mayeuf-Louchart, Alicia/0000-0002-3787-7450; 												2044-5040					AUG 6	2018	8								25	10.1186/s13395-018-0171-0							WOS:000440847200001	30081940					
J	Szunerits, S; Boukherroub, R				Szunerits, Sabine; Boukherroub, Rabah			Graphene-based nanomaterials in innovative electrochemistry	CURRENT OPINION IN ELECTROCHEMISTRY																	Szunerits, Sabine/0000-0002-1567-4943												2451-9103					AUG	2018	10						24	30		10.1016/j.coelec.2018.03.016							WOS:000442800000006						
J	Okyay, G; Bellayer, S; Samyn, F; Jimenez, M; Bourbigot, S				Okyay, G.; Bellayer, S.; Samyn, F.; Jimenez, M.; Bourbigot, S.			Characterization of in-flame soot from balsa composite combustion during mass loss cone calorimeter tests	POLYMER DEGRADATION AND STABILITY												Soot is one of the degradation products of material burning, having the fingerprints of the conditions in which it is formed. In this work, in-flame soot was probed from flaming combustion of balsa core and its sandwich composite at different heat flux scenarios during mass loss cone calorimeter tests. Soot probing was performed by thermophoresis. Electron microscopy was performed to analyze the size of the particulate media at multiscale. The size of the aggregates and the primary particles were found to be inherent to scenarios, i.e. materials specifications and heat flux rates. Nanoscale structure of in-flame soot was consistent with the results of thermogravimetric analysis of emitted-deposited soot. This semi-quantitative study contributes to soot observations in fire scenarios and constitutes the first application of soot probing by thermophoresis in a bench-scale fire scenario simulated by cone calorimetry. Technique shall be used in future to support emitted soot and smoke data. (C) 2018 Elsevier Ltd. All rights reserved.					Bourbigot, Serge/0000-0003-1536-2015; Okyay, Gizem/0000-0002-9661-6728												0141-3910	1873-2321				AUG	2018	154						304	311		10.1016/j.polymdegradstab.2018.06.013							WOS:000441488100031						
J	Wefers, J; van Moorsel, D; Hansen, J; Connell, NJ; Havekes, B; Hoeks, J; Lichtenbelt, WDV; Duez, H; Phielix, E; Kalsbeek, A; Boekschoten, MV; Hooiveld, GJ; Hesselink, MKC; Kersten, S; Staels, B; Scheer, FAJL; Schrauwen, P				Wefers, Jakob; van Moorsel, Dirk; Hansen, Jan; Connell, Niels J.; Havekes, Bas; Hoeks, Joris; Lichtenbelt, Wouter D. van Marken; Duez, Helene; Phielix, Esther; Kalsbeek, Andries; Boekschoten, Mark V.; Hooiveld, Guido J.; Hesselink, Matthijs K. C.; Kersten, Sander; Staels, Bart; Scheer, Frank A. J. L.; Schrauwen, Patrick			Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA												Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes. However, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young lean men [age 22.4 +/- 2.8 years; body mass index (BMI) 22.3 +/- 2.1 kg/m(2) (mean +/- SD)] after a 3-d control protocol and a 3.5-d misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that short-term circadian misalignment results in a significant decrease in muscle insulin sensitivity due to a reduced skeletal muscle nonoxidative glucose disposal (rate of disappearance: 23.7 +/- 2.4 vs. 18.4 +/- 1.4 mg/kg per minute; control vs. misalignment; P = 0.024). Fasting glucose and free fatty acid levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the inverted behavioral cycle, and transcriptome analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misalignment. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.				Hooiveld, Guido JEJ/F-4912-2010; Phielix, Esther/U-8149-2018; Duez, Helene/AAC-3217-2019; Kalsbeek, Andries/H-3076-2019; Scheer, Frank A.J.L./C-2795-2012; Staels, Bart/N-9497-2016	Hooiveld, Guido JEJ/0000-0003-1954-3542; Phielix, Esther/0000-0002-2672-0415; Duez, Helene/0000-0002-4130-7987; Staels, Bart/0000-0002-3784-1503; schrauwen, patrick/0000-0002-0973-847X; Scheer, Frank/0000-0002-2014-7582												0027-8424					JUL 24	2018	115	30					7789	7794		10.1073/pnas.1722295115							WOS:000439574700061	29987027					
J	Knopf, J; Magorivska, I; Maier, JM; Spitzer, P; Bilyy, R; Biermann, MHC; Hychka, K; Bondt, A; Wuhrer, M; Toes, REM; Schett, G; Herrmann, M; Munoz, LE				Knopf, Jasmin; Magorivska, Iryna; Maier, Juan M.; Spitzer, Philipp; Bilyy, Rostyslav; Biermann, Mona H. C.; Hychka, Kateryna; Bondt, Albert; Wuhrer, Manfred; Toes, Rene E. M.; Schett, Georg; Herrmann, Martin; Munoz, Luis E.			Low amounts of bisecting glycans characterize cerebrospinal fluid-borne IgG	JOURNAL OF NEUROIMMUNOLOGY												Immunoglobulin G (IgG) harbors a conserved N-glycosylation site which is important for its effector functions. Changes in glycosylation of IgG occur in many autoimmune diseases but also in physiological conditions. Therefore, the glycosylation pattern of serum IgG is well characterized. However, limited data is available on the glycosylation pattern of IgG in cerebrospinal fluid (CSF) compared to serum. Here, we report significantly reduced levels of bisected glycans in CSF IgG. Galactosylation and sialylation of IgG4 also differed significantly. Therefore, we propose a common mechanism mediating glycosylation changes of IgG at the transition from serum to CSF in steady state conditions.				Munoz, Luis E/E-7725-2010; Bilyy, Rostyslav/A-9777-2010; Herrmann, Martin/A-9597-2013; Bondt, Albert/B-2766-2015	Munoz, Luis E/0000-0002-5395-804X; Bilyy, Rostyslav/0000-0002-2344-1349; Herrmann, Martin/0000-0002-0258-2484; Bondt, Albert/0000-0002-0985-7903; Toes, Rene/0000-0002-9618-6414; Hychka, Kateryna/0000-0001-5406-3654; Wuhrer, Manfred/0000-0002-0814-4995												0165-5728	1872-8421				JUL 15	2018	320						19	24		10.1016/j.jneuroim.2018.04.010							WOS:000434748900004	29759137					
J	Jijie, R; Barras, A; Teslaru, T; Topala, I; Pohoata, V; Dobromir, M; Dumych, T; Bouckaert, J; Szunerits, S; Dumitrascu, N; Boukherroub, R				Jijie, Roxana; Barras, Alexandre; Teslaru, Teodora; Topala, Ionut; Pohoata, Valentin; Dobromir, Marius; Dumych, Tetiana; Bouckaert, Julie; Szunerits, Sabine; Dumitrascu, Nicoleta; Boukherroub, Rabah			Aqueous medium-induced micropore formation in plasma polymerized polystyrene: an effective route to inhibit bacteria adhesion	JOURNAL OF MATERIALS CHEMISTRY B												Plasma polymerized styrene (pPS) films were successfully synthesized by means of an atmospheric pressure plasma technique, using a mixture of argon gas and styrene vapor. The morphology and film thickness of the pPS films, deposited on 1 min argon plasma pre-treated glass substrates, were smooth and uniform without any visible features across the whole length of the substrates, and the films displayed a water contact angle of similar to 83 degrees. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) analysis confirmed the presence of oxygen-containing groups and the intact aromatic ring in the pPS coating. The obtained pPS films were stable for at least 30 days in air without any visible morphological degradation or chemical changes. However, the formation of a topographical pattern with micrometer lateral size and nanometer depth level was observed upon immersion in aqueous media for 72 hours. Micropore formation was believed to originate from the solubility of low crosslinked oligomers and their subsequent extraction in aqueous media. The influence of the microstructured pPS surface in mediating the attachment of eukaryotic and prokaryotic cells was further investigated. The micro-structured pPS surface influenced the adhesion and proliferation of mammalian cells. Furthermore, we could demonstrate that these films were efficient in the prevention of Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus epidermidis (S. epidermis) adhesion and biofilm formation. Importantly, the viability of non-adherent cells and of planktonic bacteria was not affected. Postcoating of the microstructured pPS with biocompatible polydopamine did not impact on the antibacterial properties of the surface, suggesting that the polymer topography was the dominant factor. The non-biocidal pPS coating can be useful in applications where micro-organism colonization and biofilm formation need to be prevented, such as food packaging and medical equipment.				Pohoata, Valentin/R-1354-2017; Jijie, Roxana/N-6837-2017; Topala, Ionut/A-2305-2009; Dumych, Tetiana/H-9450-2018	Pohoata, Valentin/0000-0001-5554-0088; Jijie, Roxana/0000-0003-0354-943X; Topala, Ionut/0000-0002-8954-8106; Bouckaert, Julie/0000-0001-8112-1442; Dumych, Tetiana/0000-0002-8489-5600; Szunerits, Sabine/0000-0002-1567-4943												2050-750X	2050-7518				JUN 14	2018	6	22					3674	3683		10.1039/c7tb02964k							WOS:000434780000006						
J	Szunerits, S; Boukherroub, R				Szunerits, Sabine; Boukherroub, Rabah			Graphene-based biosensors	INTERFACE FOCUS												Reliable data obtained from analysis of DNA, proteins, bacteria and other disease-related molecules or organisms in biological samples have become a fundamental and crucial part of human health diagnostics and therapy. The development of non-invasive tests that are rapid, sensitive, specific and simple would allow patient discomfort to be prevented, delays in diagnosis to be avoided and the status of a disease to be followed up. Bioanalysis is thus a progressive discipline for which the future holds many exciting opportunities. The use of biosensors for the early diagnosis of diseases has become widely accepted as a point-of-care diagnosis with appropriate specificity in a short time. To allow a reliable diagnosis of a disease at an early stage, highly sensitive biosensors are required as the corresponding bio-markers are generally expressed at very low concentrations. In the past 50 years, various biosensors have been researched and developed encompassing a wide range of applications. This contrasts the limited number of commercially available biosensors. When it comes to sensing of biomarkers with the required picomolar (pM) sensitivity for real-time sensing of biological samples, only a handful of sensing systems have been proposed, and these are often rather complex and costly. Lately, graphene-based materials have been considered as superior over other nanomaterials for the development of sensitive biosensors. The advantages of graphene-based sensor interfaces are numerous, including enhanced surface loading of the desired ligand due to the high surface-to-volume ratio, excellent conductivity and a small band gap that is beneficial for sensitive electrical and electrochemical read-outs, as well as tunable optical properties for optical read-outs such as fluorescence and plasmonics. In this paper, we review the advances made in recent years on graphene-based biosensors in the field of medical diagnosis.					Szunerits, Sabine/0000-0002-1567-4943												2042-8898	2042-8901				JUN 6	2018	8	3							20160132	10.1098/rsfs.2016.0132							WOS:000430570600001	29696084					
J	Amiri, M; Bezaatpour, A; Jafari, H; Boukherroub, R; Szunerits, S				Amiri, Mandana; Bezaatpour, Abolfazl; Jafari, Hamed; Boukherroub, Rabah; Szunerits, Sabine			Electrochemical Methodologies for the Detection of Pathogens	ACS SENSORS												Bacterial infections remain one of the principal causes of morbidity and mortality worldwide. The number of deaths due to infections is declining every year by only 1% with a forecast of 13 million deaths in 2050. Among the 1400 recognized human pathogens, the majority of infectious diseases is caused by just a few, about 20 pathogens only. While the development of vaccinations and novel antibacterial drugs and treatments are at the forefront of research, and strongly financially supported by policy makers, another manner to limit and control infectious outbreaks is targeting the development and implementation of early warning systems, which indicate qualitatively and quantitatively the presence of a pathogen. As toxin contaminated food and drink are a potential threat to human health and consequently have a significant socioeconomic impact worldwide, the detection of pathogenic bacteria remains not only a big scientific challenge but also a practical problem of enormous significance. Numerous analytical methods, including conventional culturing and staining techniques as well as molecular methods based on polymerase chain reaction amplification and immunological assays, have emerged over the years and are used to identify and quantify pathogenic agents. While being highly sensitive in most cases, these approaches are highly time, labor, and cost consuming, requiring trained personnel to perform the frequently complex assays. A great challenge in this field is therefore to develop rapid, sensitive, specific, and if possible miniaturized devices to validate the presence of pathogens in cost and time efficient manners. Electrochemical sensors are well accepted powerful tools for the detection of disease-related biomarkers and environmental and organic hazards. They have also found widespread interest in the last years for the detection of waterborne and foodborne pathogens due to their label free character and high sensitivity. This Review is focused on the current electrochemical-based microorganism recognition approaches and putting them into context of other sensing devices for pathogens such as culturing the microorganism on agar plates and the polymer chain reaction (PCR) method, able to identify the DNA of the microorganism. Recent breakthroughs will be highlighted, including the utilization of microfluidic devices and immunomagnetic separation for multiple pathogen analysis in a single device. We will conclude with some perspectives and outlooks to better understand shortcomings. Indeed, there is currently no adequate solution that allows the selective and sensitive binding to a specific microorganism, that is fast in detection and screening, cheap to implement, and able to be conceptualized for a wide range of biologically relevant targets.				; amiri, mandana/G-5297-2017	Szunerits, Sabine/0000-0002-1567-4943; amiri, mandana/0000-0001-8789-5692												2379-3694					JUN	2018	3	6					1069	1086		10.1021/acssensors.8b00239							WOS:000436525800003	29756447					
J	Chekin, F; Bagga, K; Subramanian, P; Jijie, R; Singh, SK; Kurungot, S; Boukherroub, R; Szunerits, S				Chekin, Fereshteh; Bagga, Komal; Subramanian, Palaniappan; Jijie, Roxana; Singh, Santosh K.; Kurungot, Sreekumar; Boukherroub, Rabah; Szunerits, Sabine			Nucleic aptamer modified porous reduced graphene oxide/MoS2 based electrodes for viral detection: Application to human papillomavirus (HPV)	SENSORS AND ACTUATORS B-CHEMICAL												Next to graphene nanomaterials, molybdenum disulfide (MoS2) offers large surface area that can enhance its biosensing performance. In this work, we investigate the performance of glassy carbon (GC) electrodes modified successively with porous reduced graphene oxide (prGO) and molybdenum sulfide (MoS2) for the sensitive and selective detection of the L1-major capsid protein of human papilloma virus (HPV). Owing to the difficulties to perform serological assays and HPV culture efficiently, tools based on molecular recognition are becoming of great importance. We developed here an electrochemical sensor for HPV upon covalent functionalization of the electrode with an aptamer Sc5-c3, a RNA aptamer targeted against the HPV-16 L1 protein. Using differential pulse voltammetry (DPV) and an optimized sensor interface, a linear relationship between the peak current density of a redox couple such as [Fe(CN)6]4- and the concentration of HPV-16 L1 proteins in the range of 0.2-2 ng mL(-1) (3.5 pM-35.3 pM) could be reached with a detection limit of 0.1 ng mL(-1) (1.75 pM). Cross-reactivity studies demonstrated high selectivity over potential interfering species such as HPV-16 E6, opening new opportunities of the developed concept for the development of point of care devices. (C) 2018 Elsevier B.V. All rights reserved.				, Palaniappan/B-1179-2012; Kurungot, Sreekumar/M-6363-2013	, Palaniappan/0000-0003-1000-6994; Kurungot, Sreekumar/0000-0001-5446-7923													0925-4005				JUN 1	2018	262						991	1000		10.1016/j.snb.2018.02.065							WOS:000427460600118						
J	Denk, J; Oberhauser, F; Kornhuber, J; Wiltfang, J; Fassbender, K; Schroeter, ML; Volk, AE; Diehl-Schmid, J; Prudlo, J; Danek, A; Landwehrmeyer, B; Lauer, M; Otto, M; Jahn, H				Denk, Johannes; Oberhauser, Felix; Kornhuber, Johannes; Wiltfang, Jens; Fassbender, Klaus; Schroeter, Matthias L.; Volk, Alexander E.; Diehl-Schmid, Janine; Prudlo, Johannes; Danek, Adrian; Landwehrmeyer, Bernhard; Lauer, Martin; Otto, Markus; Jahn, Holger		FTLDc Study Grp	Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls	PLOS ONE												Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta(1-42) and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF.				Kornhuber, Johannes/B-9613-2014; Denk, Johannes/R-3740-2019; Danek, Adrian/G-7339-2011; Denk, Johannes/X-4513-2018; Otto, Markus/F-4304-2015; Jahn, Holger/A-9255-2008	Kornhuber, Johannes/0000-0002-8096-3987; Denk, Johannes/0000-0002-1759-148X; Danek, Adrian/0000-0001-8857-5383; Denk, Johannes/0000-0002-1759-148X; Otto, Markus/0000-0003-4273-4267; Jahn, Holger/0000-0003-3607-7651; Diehl-Schmid, Janine/0000-0002-7745-1382; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X; Fassbender, Klaus/0000-0003-3596-868X												1932-6203					MAY 10	2018	13	5							e0197329	10.1371/journal.pone.0197329							WOS:000431851700103	29746584					
J	Biermann, MHC; Boeltz, S; Pieterse, E; Knopf, J; Rech, J; Bilyy, R; van der Vlag, J; Tincani, A; Distler, JHW; Kronke, G; Schett, GA; Herrmann, M; Munoz, LE				Biermann, Mona H. C.; Boeltz, Sebastian; Pieterse, Elmar; Knopf, Jasmin; Rech, Juergen; Bilyy, Rostyslav; van der Vlag, Johan; Tincani, Angela; Distler, Joerg H. W.; Kroenke, Gerhard; Schett, Georg Andreas; Herrmann, Martin; Munoz, Luis E.			Autoantibodies Recognizing Secondary NEcrotic Cells Promote Neutrophilic Phagocytosis and Identify Patients With Systemic Lupus Erythematosus	FRONTIERS IN IMMUNOLOGY												Deficient clearance of apoptotic cells reportedly contributes to the etiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). Based on this knowledge, we developed a highly specific and sensitive test for the detection of SLE autoantibodies (AAb) utilizing secondary NEcrotic cell (SNEC)-derived material as a substrate. The goal of the present study was to validate the use of SNEC as an appropriate antigen for the diagnosis of SLE in large cohort of patients. We confirmed the presence of apoptotically modified autoantigens on SNEC (dsDNA, high mobility group box 1 protein, apoptosis-associated chromatin modifications, e.g., histones H3-K27-me3; H2A/H4 AcK8,12,16; and H2B-AcK12). Anti-SNEC AAb were measured in the serum of 155 patients with SLE, 89 normal healthy donors (NHD), and 169 patients with other autoimmune connective tissue diseases employing SNEC-based indirect enzyme-linked immunosorbent assay (SNEC ELISA). We compared the test performance of SNEC ELISA with the routine diagnostic tests dsDNA Farr radioimmunoassay (RIA) and nucleosome-based ELISA (anti-dsDNA-NcX-ELISA). SNEC ELISA distinguished patients with SLE with a specificity of 98.9% and a sensitivity of 70.6% from NHD clearly surpassing RIA and anti-dsDNA-NcX-ELISA. In contrast to the other tests, SNEC ELISA significantly discriminated patients with SLE from patients with rheumatoid arthritis, primary anti-phospholipid syndrome, spondyloarthropathy, psoriatic arthritis, and systemic sclerosis. A positive test result in SNEC ELISA significantly correlated with serological variables and reflected the uptake of opsonized SNEC by neutrophils. This stresses the relevance of SNECs in the pathogenesis of SLE. We conclude that SNEC ELISA allows for the sensitive detection of pathologically relevant AAb, enabling its diagnostic usage. A positive SNEC test reflects the opsonization of cell remnants by AAb, the neutrophil recruitment to tissues, and the enhancement of local and systemic inflammatory responses.				Boeltz, Sebastian/H-3594-2014; Herrmann, Martin/A-9597-2013; Munoz, Luis E/E-7725-2010	Boeltz, Sebastian/0000-0001-5227-8707; Herrmann, Martin/0000-0002-0258-2484; Munoz, Luis E/0000-0002-5395-804X												1664-3224					MAY 7	2018	9								989	10.3389/fimmu.2018.00989							WOS:000431508500001	29867966					
J	Lancel, S; Hesselink, MKC; Woldt, E; Rouille, Y; Dorchies, E; Delhaye, S; Duhem, C; Thorel, Q; Mayeuf-Louchart, A; Pourcet, B; Montel, V; Schaart, G; Beton, N; Picquet, F; Briand, O; Salles, JP; Duez, H; Schrauwen, P; Bastide, B; Bailleul, B; Staels, B; Sebti, Y				Lancel, Steve; Hesselink, Matthijs K. C.; Woldt, Estelle; Rouille, Yves; Dorchies, Emilie; Delhaye, Stephane; Duhem, Christian; Thorel, Quentin; Mayeuf-Louchart, Alicia; Pourcet, Benoit; Montel, Valerie; Schaart, Gert; Beton, Nicolas; Picquet, Florence; Briand, Olivier; Salles, Jean Pierre; Duez, Helene; Schrauwen, Patrick; Bastide, Bruno; Bailleul, Bernard; Staels, Bart; Sebti, Yasmine			Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity	JCI INSIGHT												Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2(-/-) mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.				Mayeuf-Louchart, Alicia/AAC-5102-2019; Duez, Helene/AAC-3217-2019; , Lancel/H-9047-2019; Staels, Bart/N-9497-2016; Duez, Helene/M-7609-2017; Rouille, Yves/P-2405-2016; Briand, Olivier/N-1097-2014	Mayeuf-Louchart, Alicia/0000-0002-3787-7450; Duez, Helene/0000-0002-4130-7987; , Lancel/0000-0002-3292-5433; Staels, Bart/0000-0002-3784-1503; Rouille, Yves/0000-0003-0788-9271; Sebti, Yasmine/0000-0002-1813-810X; Schaart, Gert/0000-0003-4259-9528; Duhem, Christian/0000-0003-0931-3815; Pourcet, Benoit/0000-0002-6758-5467; Briand, Olivier/0000-0003-2979-0395; Montel, Valerie/0000-0002-7286-4209; delhaye, stephane/0000-0001-9438-6730; Bastide, bruno/0000-0002-7544-463X												2379-3708					MAY 3	2018	3	9							e98081	10.1172/jci.insight.98081							WOS:000431403500004	29720572					
J	Jijie, R; Kahlouche, K; Barras, A; Yamakawa, N; Bouckaert, J; Gharbi, T; Szunerits, S; Boukherroub, R				Jijie, Roxana; Kahlouche, Karima; Barras, Alexandre; Yamakawa, Nao; Bouckaert, Julie; Gharbi, Tijani; Szunerits, Sabine; Boukherroub, Rabah			Reduced graphene oxide/polyethylenimine based immunosensor for the selective and sensitive electrochemical detection of uropathogenic Escherichia coli	SENSORS AND ACTUATORS B-CHEMICAL												Fast, reliable and selective detection of microorganisms is of uttermost importance in clinical analysis, but also in food and water quality monitoring. In this study, we report on the construction of an immunosensor for sensitive and selective electrochemical detection of uropathogenic Escherichia coli (E. coli) UTI89 bacteria in aqueous and serum samples. We took benefit of electrophoretic deposition (EPD) to prepare, in a simple, controllable and cost effective way, gold electrodes modified with thin active layers of reduced graphene oxide/polyethylenimine (rGO/PEI). While rGO exhibits high surface area and favourable electrochemical properties, the presence of abundant -NH2 groups on PEI offers a plethora of opportunities for the sensor's surface functionalization. To achieve selectivity of detection, the electrode surface was covalently modified with anti-fimbrial E. coli antibodies via amide bond formation. To minimize non-specific adsorption, the immunosensor was additionally modified with pyrene-polyethyleneglycol (pyrene-PEG) moieties prior to antibody immobilization. The detection of E. coli was based on the restriction of electron transfer of a redox mediator, in our case potassium ferrocyanide, to the rGO/PEI modified electrical transducer due to the formation of an immune complex. The developed immunosensor displayed a sigmoidal shape with a linear range of 1 x 10(1)-1 x 10(4) cfu mL(-1) (R-2 = 0.995) according to i(mu A) =-16.66-20.5 x log[E. coil] (cfu mL(-1)) and a detection limit of 10 cfu mL(-1). Additionally, the sensor performed well both in aqueous, serum and urine media, which is essential for its potential use for clinical diagnosis of pathogenic diseases. Selectivity studies showed that the immunosensor was able to discriminate between E. coli UTI89 wild-type strain and UTI89 Delta fim, without fim operon. (C) 2017 Elsevier B.V. All rights reserved.																	0925-4005					MAY 1	2018	260						255	263		10.1016/j.snb.2017.12.169							WOS:000424884300030						
J	Hecht, M; Kramer, LM; von Arnim, CAF; Otto, M; Thal, DR				Hecht, Moritz; Kraemer, Lara Maria; von Arnim, Christine A. F.; Otto, Markus; Thal, Dietmar Rudolf			Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline	ACTA NEUROPATHOLOGICA												Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid beta-protein (A beta) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary A beta deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E epsilon 4 allele. CAA type 1-associated AD cases often exhibit a more severe A beta plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related A beta plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.				Thal, Dietmar/Y-8405-2019; Otto, Markus/F-4304-2015; Thal, Dietmar R/O-7483-2018	Thal, Dietmar/0000-0002-1036-1075; Otto, Markus/0000-0003-4273-4267; Thal, Dietmar R/0000-0002-1036-1075												0001-6322	1432-0533				MAY	2018	135	5					681	694		10.1007/s00401-018-1834-y							WOS:000430288700003	29574591					
J	Dumych, T; Yamakawa, N; Sivignon, A; Garenaux, E; Robakiewicz, S; Coddeville, B; Bongiovanni, A; Bray, F; Barnich, N; Szunerits, S; Slomianny, C; Herrmann, M; Gouin, SG; Lutsyk, AD; Munoz, LE; Lafont, F; Rolando, C; Bilyy, R; Bouckaert, JMJ				Dumych, Tetiana; Yamakawa, Nao; Sivignon, Adeline; Garenaux, Estelle; Robakiewicz, Stefania; Coddeville, Bernadette; Bongiovanni, Antonino; Bray, Fabrice; Barnich, Nicolas; Szunerits, Sabine; Slomianny, Christian; Herrmann, Martin; Gouin, Sebastien G.; Lutsyk, Alexander D.; Munoz, Luis E.; Lafont, Frank; Rolando, Christian; Bilyy, Rostyslav; Bouckaert, Julie M. J.			Oligomannose-Rich Membranes of Dying Intestinal Epithelial Cells Promote Host Colonization by Adherent-Invasive E. coli	FRONTIERS IN MICROBIOLOGY												A novel mechanism is revealed by which clinical isolates of adherent-invasive Escherichia coli (AIEC) penetrate into the epithelial cell layer, replicate, and establish biofilms in Crohn's disease. AIEC uses the FimH fimbrial adhesin to bind to oligomannose glycans on the surface of host cells. Oligomannose glycans exposed on early apoptotic cells are the preferred binding targets of AIEC, so apoptotic cells serve as potential entry points for bacteria into the epithelial cell layer. Thereafter, the bacteria propagate laterally in the epithelial intercellular spaces. We demonstrate oligomannosylation at two distinct sites of a glycoprotein receptor for AIEC, carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6 or CD66c), on human intestinal epithelia. After bacterial binding, FimH interacts with CEACAM6, which then clusters. The presence of the highest-affinity epitope for FimH, oligomannose-5, on CEACAM6 is demonstrated using LC-MS/MS. As mannose-dependent infections are abundant, this mechanism might also be used by other adherent-invasive pathogens.				Munoz, Luis E/E-7725-2010; Slomianny, Christian/L-8285-2018; Herrmann, Martin/A-9597-2013; Lutsyk, Aleksander/Z-2688-2019; Dumych, Tetiana/H-9450-2018	Munoz, Luis E/0000-0002-5395-804X; Herrmann, Martin/0000-0002-0258-2484; Lutsyk, Aleksander/0000-0001-6819-804X; gouin, sebastien/0000-0002-0985-1165; Lafont, frank/0000-0001-8668-2580; Dumych, Tetiana/0000-0002-8489-5600												1664-302X					APR 18	2018	9								742	10.3389/fmicb.2018.00742							WOS:000430326300001	29720971					
J	Pourcet, B; Zecchin, M; Ferri, L; Beauchamp, J; Sitaula, S; Billon, C; Delhaye, S; Vanhoutte, J; Mayeuf-Louchart, A; Thorel, Q; Haas, JT; Eeckhoute, J; Dombrowicz, D; Duhem, C; Boulinguiez, A; Lancel, S; Sebti, Y; Burris, TP; Staels, B; Duez, HM				Pourcet, Benoit; Zecchin, Mathilde; Ferri, Lise; Beauchamp, Justine; Sitaula, Sadicha; Billon, Cyrielle; Delhaye, Stephane; Vanhoutte, Jonathan; Mayeuf-Louchart, Alicia; Thorel, Quentin; Haas, Joel T.; Eeckhoute, Jerome; Dombrowicz, David; Duhem, Christian; Boulinguiez, Alexis; Lancel, Steve; Sebti, Yasmine; Burris, Thomas P.; Staels, Bart; Duez, Helene M.			Nuclear Receptor Subfamily 1 Group D Member 1 Regulates Circadian Activity of NLRP3 Inflammasome to Reduce the Severity of Fulminant Hepatitis in Mice	GASTROENTEROLOGY												BACKGROUND & AIMS: The innate immune system responds not only to bacterial signals, but also to non-infectious danger-associated molecular patterns that activate the NLRP3 inflammasome complex after tissue injury. Immune functions vary over the course of the day, but it is not clear whether these changes affect the activity of the NLRP3 inflammasome. We investigated whether the core clock component nuclear receptor subfamily 1 group D member 1 (NR1D1, also called Rev-erba) regulates expression, activity of the NLRP3 inflammasome, and its signaling pathway. METHODS: We collected naive peritoneal macrophages and plasma, at multiple times of day, from Nr1d1(-/-) mice and their Nr1d1(+/+) littermates (controls) and analyzed expression NLRP3, interleukin 1 beta (IL1B, in plasma), and IL18 (in plasma). We also collected bone marrow-derived primary macrophages from these mice. Levels of NR1D1 were knocked down with small hairpin RNAs in human primary macrophages. Bone marrow-derived primary macrophages from mice and human primary macrophages were incubated with lipopolysaccharide (LPS) to induce expression of NLRP3, IL1B, and IL18; cells were incubated with LPS and adenosine triphosphate to activate the NLRP3 complex. We analyzed caspase 1 activity and cytokine secretion. NR1D1 was activated in primary mouse and human macrophages by incubation with SR9009; some of the cells were also incubated with an NLRP3 inhibitor or inhibitors of caspase 1. Nr1d1(-/-) mice and control mice were given intraperitoneal injections of LPS to induce peritoneal inflammation; plasma samples were isolated and levels of cytokines were measured. Nr1d1(-/-) mice, control mice, and control mice given injections of SR9009 were given LPS and D-galactosamine to induce fulminant hepatitis and MCC950 to specifically inhibit NLRP3; plasma was collected to measure cytokines and a marker of liver failure (alanine aminotransferase); liver tissues were collected and analyzed by quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry. RESULTS: In peritoneal macrophages, expression of NLRP3 and activation of its complex varied with time of day (circadian rhythm)-this regulation required NR1D1. Primary macrophages from Nr1d1(-/-) mice and human macrophages with knockdown of NR1D1 had altered expression patterns of NLRP3, compared to macrophages that expressed NR1D1, and altered patterns of IL1B and 1L18 production. Mice with disruption of Nr1d1 developed more-severe acute peritoneal inflammation and fulminant hepatitis than control mice. Incubation of macrophage with the NR1D1 activator SR9009 reduced expression of NLRP3 and secretion of cytokines. Mice given SR9009 developed less-severe liver failure and had longer survival times than mice given saline (control). CONCLUSIONS: In studies of Nr1d1(-/-) mice and human macrophages with pharmacologic activation of NR1D1, we found NR1D1 to regulate the timing of NLRP3 expression and production of inflammatory cytokines by macrophages. Activation of NR1D1 reduced the severity of peritoneal inflammation and fulminant hepatitis in mice.				Haas, Joel/R-6379-2018; Mayeuf-Louchart, Alicia/AAC-5102-2019; Dombrowicz, David/F-7044-2013; , Lancel/H-9047-2019; Duez, Helene/AAC-3217-2019; Staels, Bart/N-9497-2016; Duez, Helene/M-7609-2017; Burris, Thomas/B-3886-2016	Haas, Joel/0000-0002-0028-5988; Mayeuf-Louchart, Alicia/0000-0002-3787-7450; Dombrowicz, David/0000-0002-0485-8923; , Lancel/0000-0002-3292-5433; Duez, Helene/0000-0002-4130-7987; Staels, Bart/0000-0002-3784-1503; Ferri, Lise/0000-0003-1981-4250; Duhem, Christian/0000-0003-0931-3815; Burris, Thomas/0000-0003-2922-4449; delhaye, stephane/0000-0001-9438-6730; Pourcet, Benoit/0000-0002-6758-5467; Sebti, Yasmine/0000-0002-1813-810X												0016-5085	1528-0012				APR	2018	154	5					1449	+		10.1053/j.gastro.2017.12.019							WOS:000428978800039	29277561					
J	Moreau, C; Duce, JA; Rascol, O; Devedjian, JC; Berg, D; Dexter, D; Cabantchik, ZI; Bush, AI; Devos, D				Moreau, Caroline; Duce, James A.; Rascol, Olivier; Devedjian, Jean-Christophe; Berg, Daniela; Dexter, David; Cabantchik, Z. Ioav; Bush, Ashley I.; Devos, David		FAIRPARK-II Study Grp	Iron as a therapeutic target for Parkinson's disease	MOVEMENT DISORDERS																Bush, Ashley I/A-1186-2007; Deplanque, Dominique/E-4901-2015; Deuschl, Gunther/A-7986-2010; Berg, Daniela D/A-8728-2019; Bush, Ashley/Y-2457-2019; Devos, David/E-4059-2013	Bush, Ashley I/0000-0001-8259-9069; Deplanque, Dominique/0000-0002-4995-584X; Berg, Daniela D/0000-0001-5796-5442; Bush, Ashley/0000-0001-8259-9069; Devos, David/0000-0002-2417-799X												0885-3185	1531-8257				APR	2018	33	4			SI		568	574		10.1002/mds.27275							WOS:000429326000009	29380903					
J	Santiago, JCP; Otto, M; Kern, W; Baier, PC; Hallschmid, M				Santiago, Joao C. P.; Otto, Markus; Kern, Werner; Baier, Paul Christian; Hallschmid, Manfred			Relationship between cerebrospinal fluid concentrations of orexin A/hypocretin-1 and body composition in humans	PEPTIDES												The hypothalamic neuropeptide orexin A (hypocretin-1) is a key signal in sleep/wake regulation and promotes food intake. We investigated the relationship between cerebrospinal fluid orexin A concentrations and body composition in non-narcoleptic human subjects with a wide range of body weight to gain insight into the role of orexin A in human metabolism. We collected cerebrospinal fluid and blood samples and measured body composition by bioelectric impedance analysis in 36 subjects (16 women and 20 men) with body mass indices between 16.24 and 38.10 kg/m(2) and an age range of 19-80 years. Bivariate Pearson correlations and stepwise multiple regressions were calculated to determine associations between orexin A and body composition as well as biometric variables. Concentrations of orexin A in cerebrospinal fluid averaged 315.6 +/- 6.0 pg/ml, were comparable between sexes (p > 0.15) and unrelated to age (p > 0.66); they appeared slightly reduced in overweight/obese compared to normal-weight subjects (p = .07). Orexin A concentrations decreased with body weight (r = -0.38, p = .0229) and fat-free mass (r = -0.39, p = .0173) but were not linked to body fat mass (p > 0.24). They were inversely related to total body water (r = -0.39, p = .0174) as well as intracellular (r = -0.41, p = .0139) and extracellular water (r = -0.35, p = .0341). Intracellular water was the only factor independently associated with cerebrospinal fluid orexin A concentrations (p = .0139). We conclude that cerebrospinal fluid orexin A concentrations do not display associations with body adiposity, but are inversely related to intracellular water content. These cross-sectional findings suggest a link between orexin A signaling and the regulation of water homeostasis in humans.				Otto, Markus/F-4304-2015; Baier, Paul/H-7919-2014	Otto, Markus/0000-0003-4273-4267; 												0196-9781	1873-5169				APR	2018	102						26	30		10.1016/j.peptides.2018.02.005							WOS:000427917500004	29471000					
J	Brenner, D; Yilmaz, R; Muller, K; Grehl, T; Petri, S; Meyer, T; Grosskreutz, J; Weydt, P; Ruf, W; Neuwirth, C; Weber, M; Pinto, S; Claeys, KG; Schrank, B; Jordan, B; Knehr, A; Gunther, K; Hubers, A; Zeller, D; Kubisch, C; Jablonka, S; Sendtner, M; Klopstock, T; de Carvalho, M; Sperfeld, A; Borck, G; Volk, AE; Dorst, J; Weis, J; Otto, M; Schuster, J; Del Tredici, K; Braak, H; Danzer, KM; Freischmidt, A; Meitinger, T; Strom, TM; Ludolph, AC; Andersen, PM; Weishaupt, JH				Brenner, David; Yilmaz, Ruestem; Mueller, Kathrin; Grehl, Torsten; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Weydt, Patrick; Ruf, Wolfgang; Neuwirth, Christoph; Weber, Markus; Pinto, Susana; Claeys, Kristl G.; Schrank, Berthold; Jordan, Berit; Knehr, Antje; Guenther, Kornelia; Huebers, Annemarie; Zeller, Daniel; Kubisch, Christian; Jablonka, Sibylle; Sendtner, Michael; Klopstock, Thomas; de Carvalho, Mamede; Sperfeld, Anne; Borck, Guntram; Volk, Alexander E.; Dorst, Johannes; Weis, Joachim; Otto, Markus; Schuster, Joachim; Del Tredici, Kelly; Braak, Heiko; Danzer, Karin M.; Freischmidt, Axel; Meitinger, Thomas; Strom, Tim M.; Ludolph, Albert C.; Andersen, Peter M.; Weishaupt, Jochen H.		German ALS Network MND-NET	Hot-spot KIF5A mutations cause familial ALS	BRAIN												Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 x 10(-3)), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p. Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 x 10(-7)). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.				Kassubek, Jan/F-2774-2015; de Carvalho, Mamede/I-6295-2019; Jablonka, Sibylle/S-1843-2018; Sendtner, Michael/M-8137-2014; Pinto, Susana/L-8394-2019; Otto, Markus/F-4304-2015; Kubisch, Christian/F-1893-2011; Kassubek, Jan/O-1740-2019; Grosskreutz, Julian/G-2293-2010	Kassubek, Jan/0000-0002-7106-9270; de Carvalho, Mamede/0000-0001-7556-0158; Jablonka, Sibylle/0000-0002-4517-3760; Sendtner, Michael/0000-0002-4737-2974; Pinto, Susana/0000-0002-0727-5897; Otto, Markus/0000-0003-4273-4267; Kubisch, Christian/0000-0003-4220-0978; Kassubek, Jan/0000-0002-7106-9270; Koch, Jan Christoph/0000-0002-3778-0683; Brenner, David/0000-0002-1535-3146; Grosskreutz, Julian/0000-0001-9525-1424												0006-8950	1460-2156				MAR	2018	141		3				688	697		10.1093/brain/awx370							WOS:000426813600016	29342275					
J	Steinacker, P; Verde, F; Fang, LB; Feneberg, E; Oeckl, P; Roeber, S; Anderl-Straub, S; Danek, A; Diehl-Schmid, J; Fassbender, K; Fliessbach, K; Foerstl, H; Giese, A; Jahn, H; Kassubek, J; Kornhuber, J; Landwehrmeyer, GB; Lauer, M; Pinkhardt, EH; Prudlo, J; Rosenbohm, A; Schneider, A; Schroeter, ML; Tumani, H; von Arnim, CAF; Weishaupt, J; Weydt, P; Ludolph, AC; Yilmazer Hanke, D; Otto, M				Steinacker, Petra; Verde, Federico; Fang, Lubin; Feneberg, Emily; Oeckl, Patrick; Roeber, Sigrun; Anderl-Straub, Sarah; Danek, Adrian; Diehl-Schmid, Janine; Fassbender, Klaus; Fliessbach, Klaus; Foerstl, Hans; Giese, Armin; Jahn, Holger; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, G. Bernhard; Lauer, Martin; Pinkhardt, Elmar Hans; Prudlo, Johannes; Rosenbohm, Angela; Schneider, Anja; Schroeter, Matthias L.; Tumani, Hayrettin; von Arnim, Christine A. F.; Weishaupt, Jochen; Weydt, Patrick; Ludolph, Albert C.; Yilmazer Hanke, Deniz; Otto, Markus		FTLDc Study Grp	Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression	JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY												Objectives Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). Methods Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con). CHIT1 and neurofilament levels were determined in cerebrospinal fluid (CSF) and blood and analysed with regard to diagnostic sensitivity and specificity and prognostic performance. Additionally, postmortem tissue was analysed for CHIT1 expression. Results In ALS, CHIT1 CSF levels were higher compared with Con (p<0.0001), DCo (p<0.05) and neurodegenerative diseases (AD p<0.05, PD p<0.01, FTLD p<0.0001) except CJD. CHIT1 concentrations were correlated with ALS disease progression and severity but not with the survival time, as did neurofilaments. Serum CHIT1 levels were not different in ALS compared with any other study group. In the spinal cord of patients with ALS, but not Con, AD or CJD cases, CHIT1 was expressed in the corticospinal tract and CHIT1 staining colocalised with markers of microglia (IBA1) and macrophages (CD68). Conclusions CHIT1 concentrations in the CSF of patients with ALS may reflect the extent of microglia/macrophage activation in the white matter of the spinal cord. CHIT1 could be a potentially useful marker for differential diagnosis and prediction of disease progression in ALS and, therefore, seems suitable as a supplemental marker for patient stratification in therapeutic trials.				Kornhuber, Johannes/B-9613-2014; Danek, Adrian/G-7339-2011; Kassubek, Jan/F-2774-2015; Kassubek, Jan/O-1740-2019; Levin, Johannes/W-8686-2019; Otto, Markus/F-4304-2015; Levin, Johannes/E-4052-2010; Jahn, Holger/A-9255-2008; Giese, Armin/F-3271-2010	Kornhuber, Johannes/0000-0002-8096-3987; Danek, Adrian/0000-0001-8857-5383; Kassubek, Jan/0000-0002-7106-9270; Kassubek, Jan/0000-0002-7106-9270; Levin, Johannes/0000-0001-5092-4306; Otto, Markus/0000-0003-4273-4267; Levin, Johannes/0000-0001-5092-4306; Jahn, Holger/0000-0003-3607-7651; Giese, Armin/0000-0002-8238-4102; Diehl-Schmid, Janine/0000-0002-7745-1382; Fassbender, Klaus/0000-0003-3596-868X; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X; Oeckl, Patrick/0000-0002-7652-7023; Verde, Federico/0000-0002-3977-6995												0022-3050	1468-330X				MAR	2018	89	3					239	247		10.1136/jnnp-2017-317138							WOS:000427409200005	29142138					
J	Pourcet, B; Staels, B				Pourcet, Benoit; Staels, Bart			Alternative macrophages in atherosclerosis: not always protective!	JOURNAL OF CLINICAL INVESTIGATION												Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163(+) macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163(+) macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin: haptoglobin/CD163/HIF1 alpha-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163(+) macrophages, which previously were thought to be beneficial.				Staels, Bart/N-9497-2016	Staels, Bart/0000-0002-3784-1503; Pourcet, Benoit/0000-0002-6758-5467												0021-9738	1558-8238				MAR 1	2018	128	3					910	912		10.1172/JCI120123							WOS:000431900100007	29457787					
J	Szunerits, S; Boukherroub, R				Szunerits, Sabine; Boukherroub, Rabah			Heat: A Highly efficient Skin enhancer for Transdermal Drug Delivery	FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY												Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of examples of thermal technologies for local and systemic transdermal drug delivery will be discussed and put into perspective.																	2296-4185					FEB 15	2018	6								15	10.3389/fbioe.2018.00015							WOS:000440253300001	29497609					
J	Catry, E; Bindels, LB; Tailleux, A; Lestavel, S; Neyrinck, AM; Goossens, JF; Lobysheva, I; Plovier, H; Essaghir, A; Demoulin, JB; Bouzin, C; Pachikian, BD; Cani, PD; Staels, B; Dessy, C; Delzenne, NM				Catry, Emilie; Bindels, Laure B.; Tailleux, Anne; Lestavel, Sophie; Neyrinck, Audrey M.; Goossens, Jean-Francois; Lobysheva, Irina; Plovier, Hubert; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Bouzin, Caroline; Pachikian, Barbara D.; Cani, Patrice D.; Staels, Bart; Dessy, Chantal; Delzenne, Nathalie M.			Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction	GUT												Objective To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction. Design We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe(-/-)) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed. Results ITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe(-/-) mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation. Conclusions We demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.				Neyrinck, Audrey/AAE-7929-2019; Lestavel, Sophie/B-4658-2017; Staels, Bart/N-9497-2016; Delzenne, Nathalie/AAC-4628-2019; Bindels, Laure/T-7846-2019; D., Cani Patrice/M-8055-2016; Plovier, Hubert/F-7082-2016; TAILLEUX, Anne/R-5530-2018	Neyrinck, Audrey/0000-0002-9435-3338; Lestavel, Sophie/0000-0001-7839-4757; Staels, Bart/0000-0002-3784-1503; Delzenne, Nathalie/0000-0003-2115-6082; Bindels, Laure/0000-0003-3747-3234; D., Cani Patrice/0000-0003-2040-2448; Plovier, Hubert/0000-0001-9494-8094; TAILLEUX, Anne/0000-0003-1430-2627												0017-5749	1468-3288				FEB	2018	67	2					271	283		10.1136/gutjnl-2016-313316							WOS:000419604800012	28377388					
J	Fang, J; He, XZ; Li, KY; Wang, JW; Zhang, YM				Fang, Jun; He, Xuan-ze; Li, Kai-yuan; Wang, Jing-wu; Zhang, Yong-ming			Transition condition and control mechanism of subatmospheric flame spread rate over horizontal thin paper sample	COMBUSTION AND FLAME												The horizontal flame spread over paper samples was investigated using a subatmospheric cabin with varied O-2 concentration. The 25 kPa is found to be a clear turning point for the flame illumination and structure, radiative heat flux and flame spread rate (FSR), which leads to the transition boundary between the extinction limits and power law regions. In the extinction limits (non-linear) region below 25 kPa, the oxygen partial pressure is low with a small Da number. Consequent, the flame spread is gas phase kinetics controlled, resulting in low burning rate, low radiative heat loss and weak buoyancy, and thus the FSR is more sensitive to the oxygen concentration while less sensitive to the ambient pressure. In the power law (linear) region above 25 kPa, in contrast, the oxygen partial pressure is high and the Da number is large, and the flame spread is heat transfer controlled, which weakens the dependence of FSR on oxygen concentration and enhances the dependence on air pressure. (C) 2017 The Combustion Institute. Published by Elsevier Inc. All rights reserved.					jun, fang/0000-0001-8470-6673												0010-2180	1556-2921				FEB	2018	188						90	93		10.1016/j.combustflame.2017.09.010							WOS:000424859100008						
J	Grossmayer, GE; Keppeler, H; Boeltz, S; Janko, C; Rech, J; Herrmann, M; Lauber, K; Munoz, LE				Grossmayer, Gerhard E.; Keppeler, Hildegard; Boeltz, Sebastian; Janko, Christina; Rech, Juergen; Herrmann, Martin; Lauber, Kirsten; Munoz, Luis E.			Elevated Serum Lysophosphatidylcholine in Patients with Systemic Lupus Erythematosus Impairs Phagocytosis of Necrotic Cells In Vitro	FRONTIERS IN IMMUNOLOGY												Objectives: Impaired clearance of dying and dead cells by professional and amateur phagocytes plays a crucial role in the etiology of systemic lupus erythematosus (SLE). While dying, cells expose and release a plethora of eat-me and find-me signals to ensure their timely removal before entering the dangerous stage of secondary necrosis. A well-described chemoattractant for macrophages is dying cell-derived lysophosphatidylcholine (LPC). However, its implications for and/or its association with SLE disease, so far, have not been examined. In the present study, we analyzed the LPC serum concentrations of patients with SLE and rheumatoid arthritis (RA). Subsequently, we examined if and to which extent the measured serum concentrations of LPC and an LPC-rich environment can impact the phagocytosis of necrotic cells. Methods: Sera from patients with SLE, RA, and normal healthy donors (NHD) were characterized for several parameters, including LPC concentrations. Phagocytosis of dead cells by human macrophages in the presence of SLE and NHD sera was quantified. Additionally, the impact of exogenously added, purified LPC on phagocytosis was analyzed. Results: Patients with SLE had significantly increased LPC serum levels, and high serum LPC of SLE patients correlated significantly with impaired phagocytosis of dead cells in the presence of heat-inactivated serum. Phagocytosis in the presence of sera from NHD showed no correlation to LPC levels, but exogenous addition of purified LPC in the range as measured in SLE patients' sera led to a concentration-dependent decrease. Conclusion: Our data show that high levels of LPC as observed in the sera of SLE patients have a negative impact on the clearance of dead cells by macrophages. Chemoattraction requires a concentration gradient. The higher the LPC concentration surrounding a dying or dead cell, the smaller the achievable gradient upon LPC release will be. Thus, it is feasible to assume that elevated LPC levels can interfere with the build-up of a local LPC gradient during cell death, and hence might play a role in the establishment and/or perpetuation of SLE disease.				Boeltz, Sebastian/H-3594-2014; Munoz, Luis E/E-7725-2010; Herrmann, Martin/A-9597-2013	Boeltz, Sebastian/0000-0001-5227-8707; Munoz, Luis E/0000-0002-5395-804X; Herrmann, Martin/0000-0002-0258-2484												1664-3224					JAN 17	2018	8								1876	10.3389/fimmu.2017.01876							WOS:000422682900001						
J	Feneberg, E; Oeckl, P; Steinacker, P; Verde, F; Barro, C; Van Damme, P; Gray, E; Grosskreutz, J; Jardel, C; Kuhle, J; Koerner, S; Lamari, F; Amador, MD; Mayer, B; Morelli, C; Muckova, P; Petri, S; Poesen, K; Raaphorst, J; Salachas, F; Silani, V; Stubendorff, B; Turner, MR; Verbeek, MM; Weishaupt, JH; Weydt, P; Ludolph, AC; Otto, M				Feneberg, Emily; Oeckl, Patrick; Steinacker, Petra; Verde, Federico; Barro, Christian; Van Damme, Philip; Gray, Elizabeth; Grosskreutz, Julian; Jardel, Claude; Kuhle, Jens; Koerner, Sonja; Lamari, Foudil; Amador, Maria del Mar; Mayer, Benjamin; Morelli, Claudia; Muckova, Petra; Petri, Susanne; Poesen, Koen; Raaphorst, Joost; Salachas, Francois; Silani, Vincenzo; Stubendorff, Beatrice; Turner, Martin R.; Verbeek, Marcel M.; Weishaupt, Jochen H.; Weydt, Patrick; Ludolph, Albert C.; Otto, Markus			Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis	NEUROLOGY												ObjectiveTo examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS).MethodsWe measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset 6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures.ResultsNfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%, 78%) and specificity (86%, 92%, 91%, and 94%, 90%, 98%) and did not vary between clinical diagnostic categories of ALS in the early symptomatic phase group. Baseline NfL and pNfH levels were not significantly different in patients with ALS with clinical progression to definite or probable ALS at follow-up.ConclusionThe measurement of Nf has potential to enhance diagnostic accuracy of ALS in those presenting soon after symptom onset, and is measurable across multiple centers.Classification of evidenceThis study provides Class II evidence that CSF and serum Nf concentrations discriminate ALS with early symptom onset from other neurologic diseases.				Grosskreutz, Julian/G-2293-2010; Van Damme, Philip/A-6464-2009; Verbeek, Marcel M/D-1971-2010; Otto, Markus/F-4304-2015	Grosskreutz, Julian/0000-0001-9525-1424; Van Damme, Philip/0000-0002-4010-2357; Verbeek, Marcel M/0000-0003-4635-7876; Otto, Markus/0000-0003-4273-4267; Verde, Federico/0000-0002-3977-6995; Turner, Martin/0000-0003-0267-3180; Oeckl, Patrick/0000-0002-7652-7023; Barro, Christian/0000-0002-7795-7383												0028-3878	1526-632X				JAN 2	2018	90	1					E22	E30		10.1212/WNL.0000000000004761							WOS:000427797500003	29212830					
J	Podolska, MJ; Mahajan, A; Knopf, J; Hahn, J; Boeltz, S; Munoz, L; Bilyy, R; Herrmann, M				Podolska, Malgorzata Justyna; Mahajan, Aparna; Knopf, Jasmin; Hahn, Jonas; Boeltz, Sebastian; Munoz, Luis; Bilyy, Rostyslav; Herrmann, Martin			Autoimmune, rheumatic, chronic inflammatory diseases: Neutrophil extracellular traps on parade	AUTOIMMUNITY												Rheumatic diseases are a group of inflammatory conditions that affect joints and connective tissues and are often accompanied by pain and restriction of motility. In many of these diseases, autoantibodies develop that react with molecules/structures commonly found hidden in neutrophils. Neutrophil extracellular trap (NET) formation and release is considered a defense mechanism against pathogens or endogenous danger signals and it has been associated with initial inflammatory responses. NETs are also endowed with an important resolution potential based on its intrinsic enzymatic activity, but in the case they are not timely removed from the crime scene they might modulate subsequent immune responses and contribute to the pathogenesis of chronic inflammatory diseases. In this review, we will summarize the actual knowledge about the multifaceted roles of NETs in the etiology and pathogenesis of rheumatic autoimmune diseases.				Herrmann, Martin/A-9597-2013; Boeltz, Sebastian/H-3594-2014; Munoz, Luis E/E-7725-2010; Bilyy, Rostyslav/A-9777-2010	Herrmann, Martin/0000-0002-0258-2484; Boeltz, Sebastian/0000-0001-5227-8707; Munoz, Luis E/0000-0002-5395-804X; Bilyy, Rostyslav/0000-0002-2344-1349; Hahn, Jonas/0000-0003-3944-2108												0891-6934	1607-842X					2018	51	6					281	287		10.1080/08916934.2018.1519804							WOS:000452838700003	30369262					
J	Appelgren, D; Dahle, C; Knopf, J; Bilyy, R; Vovk, V; Sundgren, PC; Bengtsson, AA; Wettero, J; Munoz, LE; Herrmann, M; Hoog, A; Sjowall, C				Appelgren, Daniel; Dahle, Charlotte; Knopf, Jasmin; Bilyy, Rostyslav; Vovk, Volodymyr; Sundgren, Pia C.; Bengtsson, Anders A.; Wettero, Jonas; Munoz, Luis E.; Herrmann, Martin; Hoog, Anders; Sjowall, Christopher			Active NET formation in Libman-Sacks endocarditis without antiphospholipid antibodies: A dramatic onset of systemic lupus erythematosus	AUTOIMMUNITY												Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman-Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman-Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sex-matched blood donors (p=.0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r=0.65, p=.16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman-Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE.				Bilyy, Rostyslav/A-9777-2010; Munoz, Luis E/E-7725-2010; Wettero, Jonas/C-9578-2009; Sjoewall, Christoffer/C-9678-2009; Herrmann, Martin/A-9597-2013; Appelgren, Daniel/O-1264-2018	Bilyy, Rostyslav/0000-0002-2344-1349; Munoz, Luis E/0000-0002-5395-804X; Wettero, Jonas/0000-0002-6916-5490; Sjoewall, Christoffer/0000-0003-0900-2048; Herrmann, Martin/0000-0002-0258-2484; Appelgren, Daniel/0000-0002-3328-5060; Vovk, Volodymyr/0000-0002-8411-267X; Sundgren, Pia/0000-0001-9237-1236												0891-6934	1607-842X					2018	51	6					310	318		10.1080/08916934.2018.1514496							WOS:000452838700007	30369267					
J	Dubois-Chevalier, J; Mazrooei, P; Lupien, M; Staels, B; Lefebvre, P; Eeckhoute, J				Dubois-Chevalier, Julie; Mazrooei, Parisa; Lupien, Mathieu; Staels, Bart; Lefebvre, Philippe; Eeckhoute, Jerome			Organizing combinatorial transcription factor recruitment at cis-regulatory modules	TRANSCRIPTION-AUSTIN												Gene transcriptional regulation relies on cis-regulatory DNA modules (CRMs), which serve as nexus sites for integration of multiple transcription factor (TF) activities. Here, we provide evidence and discuss recent literature indicating that TF recruitment to CRMs is organized into combinations of trans-regulatory protein modules (TRMs). We propose that TRMs are functional entities composed of TFs displaying the most highly interdependent chromatin binding which are, in addition, able to modulate their recruitment to CRMs through inter-TRM effects. These findings shed light on the architectural organization of TF recruitment encoded by their recognition motifs within CRMs.				Lefebvre, Philippe/F-2685-2010; Staels, Bart/N-9497-2016	Lefebvre, Philippe/0000-0002-9366-5129; Staels, Bart/0000-0002-3784-1503; Dubois-Chevalier, Julie/0000-0003-0471-752X												2154-1264	2154-1272					2018	9	4					233	239		10.1080/21541264.2017.1394424							WOS:000442397300003	29105538					
J	Oeckl, P; Steinacker, P; Otto, M				Oeckl, Patrick; Steinacker, Petra; Otto, Markus			Comparison of Internal Standard Approaches for SRM Analysis of Alpha-Synuclein in Cerebrospinal Fluid	JOURNAL OF PROTEOME RESEARCH												Absolute protein quantification by selected reaction monitoring (SRM, also MRM) is an alternative to immunoassays, and the gold standard here is the addition of stable-isotope labeled (SIL) proteins (PSAQ). Cerebrospinal (CSF) is the preferred source of biomarkers for neurological diseases, and recent improvements in mass spectrometry enable the quantification of disease-relevant proteins in CSF. We used alpha-synudein SRM to investigate alternatives to the PSAQ approach in human CSF regarding precision and accuracy, including SIL peptides, winged SIL (WiSIL) peptides, and quantitative protein epitope signature tags (QPrESTs). All approaches yielded precise results in CSF with CV values <15% in several runs for all four measured peptides. PSAQ and QPrEST also showed good accuracy (deviation <15%), whereas SIL and WiSIL peptides yielded deviations up to 54% that greatly depended on the measured peptide. Total protein concentration in CSF did not affect precision and accuracy. Thus, our study indicates that all four approaches are suitable for relative quantification of alpha-synuclein in CSF. QPrESTs are a valuable alternative to PSAQ in terms of precision and accuracy, although SIL and WiSIL peptides can yield accurate results as well when peptides are selected consciously.				Otto, Markus/F-4304-2015	Otto, Markus/0000-0003-4273-4267; Oeckl, Patrick/0000-0002-7652-7023												1535-3893	1535-3907				JAN	2018	17	1					516	523		10.1021/acs.jproteome.7b00660							WOS:000419749800047	29183121					
J	Jijie, R; Barras, A; Boukherroub, R; Szunerits, S				Jijie, Roxana; Barras, Alexandre; Boukherroub, Rabah; Szunerits, Sabine			Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures	JOURNAL OF MATERIALS CHEMISTRY B												A wide range of biomedical materials have been proposed to meet the different needs for controlled oral or intravenous drug delivery. The advantages of oral delivery such as self-administration of a pre-determined drug dose at defined time intervals makes it the most convenient means for the delivery of small molecular drugs. It fails however to delivery therapeutic macromolecules due to rapid degradation in the stomach and size-limited transport across the epithelium. The primary mode of administration of macromolecules is presently via injection. This administration mode is not without limitations, as the invasive nature of injections elicits pain and decreases patients' compliance. Alternative routes for drug delivery have been looked for, one being the skin. Delivery of drugs via the skin is based on the therapeutics penetrating the stratum corneum (SC) with the advantage of overcoming first-pass metabolism of drugs, to deliver drugs with a short-half-life time more easily and to eliminate frequent administrations to maintain constant drug delivery. The transdermal market still remains limited to a narrow range of drugs. The low permeability of the SC to water-soluble and macromolecular drugs poses significant challenges to transdermal administration via passive diffusion through the skin, as is the case for all topically administered drug formulations intended to bring the therapeutic into the general circulation. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to the integration of skin enhancers into pharmaceutical formulations, nanoparticles based on lipid carriers have been widely considered and reviewed. While being briefly reviewed here, the main focus of this article is on current advancements using polymeric and metallic nanoparticles. Next to these passive technologies, the handful of active technologies for local and systemic transdermal drug delivery will be discussed and put into perspective. While passive approaches dominate the literature and the transdermal market, active delivery based on microneedles or iontophoresis approaches have shown great promise for transdermal drug delivery and have entered the market, in the last decade. This review gives an overall idea of the current activities in this field.				; Jijie, Roxana/N-6837-2017	Szunerits, Sabine/0000-0002-1567-4943; Jijie, Roxana/0000-0003-0354-943X												2050-750X	2050-7518				NOV 28	2017	5	44					8653	8675		10.1039/c7tb02529g							WOS:000415354000002						
J	Munoz, LE; Leppkes, M; Fuchs, TA; Hoffmann, M; Herrmann, M				Munoz, Luis E.; Leppkes, Moritz; Fuchs, Tobias A.; Hoffmann, Markus; Herrmann, Martin			Missing in action-The meaning of cell death in tissue damage and inflammation	IMMUNOLOGICAL REVIEWS												Billions of cells die every day in higher organisms as part of the normal process of tissue homeostasis. During special conditions like in development, acute infections, mechanical injuries, and immunity, cell death is a common denominator and it exerts profound effects in the outcome of these scenarios. To prevent the accumulation of aged, superfluous, infected, damaged and dead cells, professional phagocytes act in a rapid and efficient manner to clear the battle field and avoid spread of the destruction. Neutrophils are the most abundant effector immune cells that extravasate into tissues and can turn injured tissues into gory battle fields. In peace times, neutrophils tend to patrol tissues without provoking inflammatory reactions. We discuss in this review actual and forgotten knowledge about the meaning of cell death during homeostatic processes and drive the attention to the importance of the action of neutrophils during patrolling and for the maintenance or recovery of the homeostatic state once the organism gets attacked or injured, respectively. In this fashion, we disclose several disease conditions that arise as collateral damage of physiological responses to death.				Leppkes, Moritz/N-2932-2017; Munoz, Luis E/E-7725-2010; Herrmann, Martin/A-9597-2013	Munoz, Luis E/0000-0002-5395-804X; Herrmann, Martin/0000-0002-0258-2484; Hoffmann, Markus/0000-0001-9698-9922												0105-2896	1600-065X				NOV	2017	280	1			SI		26	40		10.1111/imr.12569							WOS:000412895600003	29027227					
J	Halouane, F; Jijie, R; Meziane, D; Li, CN; Singh, SK; Bouckaert, J; Jurazek, J; Kurungot, S; Barras, A; Li, MS; Boukherroub, R; Szunerits, S				Halouane, Fatima; Jijie, Roxana; Meziane, Dalila; Li, Chengnan; Singh, Santosh K.; Bouckaert, Julie; Jurazek, Jean; Kurungot, Sreekumar; Barras, Alexandre; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine			Selective isolation and eradication of E. coli associated with urinary tract infections using anti-fimbrial modified magnetic reduced graphene oxide nanoheaters	JOURNAL OF MATERIALS CHEMISTRY B												The fast and efficient elimination of pathogenic bacteria from water, food or biological samples such as blood remains a challenging task. Magnetic isolation of bacteria from complex media holds particular promise for water disinfection and other biotechnological applications employing bacteria. When it comes to infectious diseases such as urinary tract infections, the selective removal of the pathogenic species in complex media such as human serum is also of importance. This issue can only be accomplished by adding pathogen specific targeting sites onto the magnetic nanostructures. In this work, we investigate the potential of 2-nitrodopamine modified magnetic particles anchored on reduced graphene oxide (rGO) nanocomposites for rapid capture and efficient elimination of E. coli associated with urinary tract infections (UTIs) from water and serum samples. An optimized magnetic nanocarrier achieves a 99.9% capture efficiency even at E. coli concentrations of 1 x 10(1) cfu mL(-1) in 30 min. In addition, functionalization of the nanostructures with poly(ethylene glycol) modified pyrene units and anti-fimbrial E. coli antibodies allowed specific elimination of E. coli UTI89 from serum samples. Irradiation of the E. coli loaded nanocomposite with a near-infrared laser results in the total ablation of the captured pathogens. This method can be flexibly modified for any other pathogenic bacteria, depending on the antibodies used, and might be an interesting alternative material for a magnetic-based body fluid purification approach.				; Kurungot, Sreekumar/M-6363-2013; Jijie, Roxana/N-6837-2017	Bouckaert, Julie/0000-0001-8112-1442; Kurungot, Sreekumar/0000-0001-5446-7923; Szunerits, Sabine/0000-0002-1567-4943; Jijie, Roxana/0000-0003-0354-943X												2050-750X	2050-7518				OCT 28	2017	5	40					8133	8142		10.1039/c7tb01890h							WOS:000413200500010						
J	Li, CN; Ye, R; Bouckaert, J; Zurutuza, A; Drider, D; Dumych, T; Paryzhak, S; Vovk, V; Bilyy, RO; Melinte, S; Li, M; Boukherroub, R; Szunerits, S				Li, Chengnan; Ye, Ran; Bouckaert, Julie; Zurutuza, Amaia; Drider, Djamel; Dumych, Tetiana; Paryzhak, Solomiya; Vovk, Volodymyr; Bilyy, Rostyslav O.; Melinte, Sorin; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine			Flexible Nanoholey Patches for Antibiotic-Free Treatments of Skin Infections	ACS APPLIED MATERIALS & INTERFACES												Despite the availability of different antibiotics, bacterial infections are still one of the leading causes of try hospitalization and mortality. The clinical failure of antibiotic treatment is due to a general poor antibiotic penetration to bacterial infection sites as well as the development of antibiotic-resistant pathogens. In the case of skin infection, the wound is covered by exudate, making it impermeable to topical antibiotics. The development of a flexible patch allowing a rapid and highly efficient treatment of subcutaneous wound infections via photothermal irradiation is presented here. The skin patch combines the near-infrared photothermal properties of a gold nanohole array formed by self-assembly of colloidal structures on flexible polyimide films with that of reduced graphene oxide nanosheets for laser-gated pathogen inactivation. In vivo tests performed on mice with subcutaneous skin infection and treated with the photothermal skin patch show wound healing of the infected site, while nontreated areas result in necrotic muscular fibers and bacterial infiltrate. No loss in efficiency is observed upon multiple use of these patches during in vivo experiments because of their robustness.				Dumych, Tetiana/H-9450-2018; Bilyy, Rostyslav/A-9777-2010; Melinte, Sorin/A-7009-2010; Paryzhak, Solomiya/G-4819-2019	Dumych, Tetiana/0000-0002-8489-5600; Bilyy, Rostyslav/0000-0002-2344-1349; Melinte, Sorin/0000-0003-2176-554X; Paryzhak, Solomiya/0000-0002-1491-3711; Vovk, Volodymyr/0000-0002-8411-267X; Szunerits, Sabine/0000-0002-1567-4943												1944-8244					OCT 25	2017	9	42					36665	36674		10.1021/acsami.7b12949							WOS:000414115700019	28956593					
J	Oz, Y; Barras, A; Sanyal, R; Boukherroub, R; Szunerits, S; Sanyal, A				Oz, Yavuz; Barras, Alexandre; Sanyal, Rana; Boukherroub, Rabah; Szunerits, Sabine; Sanyal, Amitav			Functionalization of Reduced Graphene Oxide via Thiol-Maleimide "Click" Chemistry: Facile Fabrication of Targeted Drug Delivery Vehicles	ACS APPLIED MATERIALS & INTERFACES												Materials based on reduced graphene oxide (rGO) have shown to be amenable to noncovalent functionalization through hydrophobic interactions. The scaffold, however, does not provide sufficient covalent linkage given the low number of reactive carboxyl and alcohol groups typically available on the rGO. The integration of clickable groups, particularly the ones that can undergo efficient conjugation without any metal catalyst, would allow facile functionalization of these materials. This study reports on the noncovalent association of a maleirmde-containing catechol (dopa-MAL) surface anchor onto the rGO. Thiol-maleimide chemistry allows thereafter the facile attachment of thiol-containing molecules under ambient metal-free conditions. Although the attachment of glutathione and 6-(ferrocenyl)hexanethiol was used as model thiols, the attachment of a cancer cell targeting cyclic peptide, c(RGDfC), opened the possibility of using the dopa-MAL-modified rGO as a targeted drug delivery system for doxorubicin (DOX). Although free DOX showed to be more effective at killing the human cervical cancer cells (HeLa) over human breast adenocarcinoma cancer cells (MDA-MB-231), the DOX-loaded rGO/dopa-MAL-c (RGDfC) nanostructure showed an opposite effect being notably more effective at targeting and killing the MDA-MB-231 cells. The effect is enhanced upon laser irradiation for 10 min at 2 W cm(-2). The facile fabrication and functionalization to readily obtain a functional material in a modular fashion make this clickable-rGO construct an attractive platform for various applications.				; /I-4328-2013	Szunerits, Sabine/0000-0002-1567-4943; /0000-0001-5122-8329												1944-8244	1944-8252				OCT 4	2017	9	39					34194	34203		10.1021/acsami.7b08433							WOS:000412717600095	28905618					
J	Legry, V; Francque, S; Haas, JT; Verrijken, A; Caron, S; Chavez-Talavera, O; Vallez, E; Vonghia, L; Dirinck, E; Verhaegen, A; Kouach, M; Lestavel, S; Lefebvre, P; Van Gaal, L; Tailleux, A; Paumelle, R; Staels, B				Legry, Vanessa; Francque, Sven; Haas, Joel T.; Verrijken, An; Caron, Sandrine; Chavez-Talavera, Oscar; Vallez, Emmanuelle; Vonghia, Luisa; Dirinck, Eveline; Verhaegen, Ann; Kouach, Mostafa; Lestavel, Sophie; Lefebvre, Philippe; Van Gaal, Luc; Tailleux, Anne; Paumelle, Rejane; Staels, Bart			Bile Acid Alterations Are Associated With Insulin Resistance, but Not With NASH, in Obese Subjects	JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM												Context: Bile acids (BAs) are signaling molecules controlling energy homeostasis that can be both toxic and protective for the liver. BA alterations have been reported in obesity, insulin resistance (IR), and nonalcoholic steatohepatitis (NASH). However, whether BA alterations contribute to NASH independently of the metabolic status is unclear. Objective: To assess BA alterations associated with NASH independently of body mass index and IR. Design and Setting: Patients visiting the obesity clinic of the Antwerp University Hospital (a tertiary referral facility) were recruited from 2006 to 2014. Patients: Obese patients with biopsy-proven NASH (n = 32) and healthy livers (n = 26) were matched on body mass index and homeostasis model assessment of IR. Main Outcome Measures: Transcriptomic analyses were performed on liver biopsies. Plasma concentrations of 21 BA species and 7 alpha-hydroxy-4-cholesten-3-one, a marker of BA synthesis, were determined by liquid chromatography-tandem mass spectrometry. Plasma fibroblast growth factor 19 was measured by enzyme-linked immunosorbent assay. Results: Plasma BA concentrations did not correlate with any hepatic lesions, whereas, as previously reported, primary BA strongly correlated with IR. Transcriptomic analyses showed unaltered hepatic BA metabolism in NASH patients. In line, plasma 7 alpha-hydroxy-4-cholesten-3-one was unchanged in NASH. Moreover, no sign of hepaticBAaccumulation or activation of BA receptors-farnesoid X, pregnane X, and vitamin Dreceptors-was found. Finally, plasma fibroblast growth factor 19, secondary-to-primary BA, and free-to-conjugated BA ratios were similar, suggesting unaltered intestinal BA metabolism and signaling. Conclusions: In obese patients, BA alterations are related to the metabolic phenotype associated with NASH, especially IR, but not liver necroinflammation.				Lefebvre, Philippe/F-2685-2010; CARON, Sandrine/R-6624-2018; Staels, Bart/N-9497-2016; Lestavel, Sophie/B-4658-2017; Paumelle, Rejane/R-6675-2018; Haas, Joel/R-6379-2018; TAILLEUX, Anne/R-5530-2018	Lefebvre, Philippe/0000-0002-9366-5129; CARON, Sandrine/0000-0002-4660-7436; Staels, Bart/0000-0002-3784-1503; Lestavel, Sophie/0000-0001-7839-4757; Paumelle, Rejane/0000-0002-4489-0717; Haas, Joel/0000-0002-0028-5988; TAILLEUX, Anne/0000-0003-1430-2627												0021-972X	1945-7197				OCT 1	2017	102	10					3783	3794		10.1210/jc.2017-01397							WOS:000412450400019	28938455					
J	Jijie, R; Barras, A; Teodorescu, F; Boukherroub, R; Szunerits, S				Jijie, Roxana; Barras, Alexandre; Teodorescu, Florina; Boukherroub, Rabah; Szunerits, Sabine			Advancements on the molecular design of nanoantibiotics: current level of development and future challenges	MOLECULAR SYSTEMS DESIGN & ENGINEERING												Numerous antimicrobial drugs have been developed and commercialized to kill and inhibit the growth of pathogenic microbes. The therapeutic efficiency of these drugs has however become often inadequate for the treatment of microbial infections, the reasons being multiple. Oral administration results often in only partial absorption and up to 50% of the active compound can be excreted in the urine. Furthermore, antibiotic therapy is also frequently accompanied by gastrointestinal complications, including vomiting, nausea and diarrhea. From a therapeutic point of view, the low solubility of antibiotics in lipid membranes presents a limitation for rapid and efficient treatment of infections. The preferred route for the delivery of antimicrobial drugs is the oral one; oral formulations capable of extending the duration of drug delivery and minimizing side effects have received much attention. The combination of antimicrobial agents with nano-materials has been seen as a particularly promising strategy to overcome these limitations. Particulate formulations have proven their efficiency in achieving better pharmacokinetic profiles and improving the bio availability of several antibiotics. Antibiotic modified particles have shown their capability to protect some of the antimicrobial drugs from stomach acid and first-pass metabolisms in the gastrointestinal tract. Likewise, particle formulations can increase the circulation times of a drug and the local concentration gradient across absorptive cells. The present review describes the current status of different types of antibiotic loaded nano-systems. Key principles such as antibiotic loading, the release mechanism and the mode of action involved in pathogen killing or inhibition will be discussed in more detail. It is hoped that the general knowledge obtained here will help in the generation of advanced nanomaterials loaded with antimicrobials agents.					Szunerits, Sabine/0000-0002-1567-4943												2058-9689					OCT 1	2017	2	4					349	369		10.1039/c7me00048k							WOS:000412769000002						
J	Pham, MH; Elshehabi, M; Haertner, L; Del Din, S; Srulijes, K; Heger, T; Synofzik, M; Hobert, MA; Faber, GS; Hansen, C; Salkovic, D; Ferreira, JJ; Berg, D; Sanchez-Ferro, A; van Dieen, JH; Becker, C; Rochester, L; Schmidt, G; Maetzler, W				Pham, Minh H.; Elshehabi, Morad; Haertner, Linda; Del Din, Silvia; Srulijes, Karin; Heger, Tanja; Synofzik, Matthis; Hobert, Markus A.; Faber, Gert S.; Hansen, Clint; Salkovic, Dina; Ferreira, Joaquim J.; Berg, Daniela; Sanchez-Ferro, Alvaro; van Dieen, Jaap H.; Becker, Clemens; Rochester, Lynn; Schmidt, Gerhard; Maetzler, Walter			Validation of a step detection Algorithm during straight Walking and turning in Patients with Parkinson's disease and older Adults Using an Inertial Measurement Unit at the Lower Back	FRONTIERS IN NEUROLOGY												Introduction: Inertial measurement units (IMUs) positioned on various body locations allow detailed gait analysis even under unconstrained conditions. From a medical perspective, the assessment of vulnerable populations is of particular relevance, especially in the daily-life environment. Gait analysis algorithms need thorough validation, as many chronic diseases show specific and even unique gait patterns. The aim of this study was therefore to validate an acceleration-based step detection algorithm for patients with Parkinson's disease (PD) and older adults in both a lab-based and home-like environment. Methods: In this prospective observational study, data were captured from a single 6-degrees of freedom IMU (APDM) (3DOF accelerometer and 3DOF gyroscope) worn on the lower back. Detection of heel strike (HS) and toe off (TO) on a treadmill was validated against an optoelectronic system (Vicon) (11 PD patients and 12 older adults). A second independent validation study in the home-like environment was performed against video observation (20 PD patients and 12 older adults) and included step counting during turning and non-turning, defined with a previously published algorithm. Results: A continuous wavelet transform (cwt)-based algorithm was developed for step detection with very high agreement with the optoelectronic system. HS detection inPD patients/older adults, respectively, reached 99/99% accuracy. Similar results were obtained for TO (99/100%). In HS detection, Bland-Altman plots showed a mean difference of 0.002 s [95% confidence interval (CI) -0.09 to 0.10] between the algorithm and the optoelectronic system. The Bland-Altman plot for TO detection showed mean differences of 0.00 s (95% CI -0.12 to 0.12). In the home-like assessment, the algorithm for detection of occurrence of steps during turning reached 90% (PD patients)/90% (older adults) sensitivity, 83/88% specificity, and 88/89% accuracy. The detection ofsteps during non-turning phases reached 91/91% sensitivity, 90/90% specificity, and 91/91% accuracy. Conclusion: This cwt-based algorithm for step detection measured at the lower back is in high agreement with the optoelectronic system in both PD patients and older adults. This approach and algorithm thus could provide a valuable tool for future research on home-based gait analysis in these vulnerable cohorts.				Berg, Daniela D/A-8728-2019; Deuschl, Gunther/A-7986-2010; van Dieen, Jaap/B-3937-2013; Del Din, Silvia/H-2863-2019; Maetzler, Walter/A-6796-2011; Hansen, Clint/J-4961-2019; Sanchez-Ferro, Alvaro/B-4265-2014	Berg, Daniela D/0000-0001-5796-5442; van Dieen, Jaap/0000-0002-7719-5585; Maetzler, Walter/0000-0002-5945-4694; Hansen, Clint/0000-0003-4813-3868; Del Din, Silvia/0000-0003-1154-4751; Sanchez-Ferro, Alvaro/0000-0003-2461-2485; Faber, Gert/0000-0003-3596-0389; Rochester, Lynn/0000-0001-5774-9272												1664-2295					SEP 4	2017	8								457	10.3389/fneur.2017.00457							WOS:000409090800002	28928711					
J	Stumer, J; Biermann, MHC; Knopf, J; Magorivska, I; Kastbom, A; Svard, A; Janko, C; Bilyy, R; Schett, G; Sjowall, C; Herrmann, M; Munoz, LE				Stuemer, J.; Biermann, M. H. C.; Knopf, J.; Magorivska, I.; Kastbom, A.; Svaerd, A.; Janko, C.; Bilyy, R.; Schett, G.; Sjoewall, C.; Herrmann, M.; Munoz, L. E.			Altered glycan accessibility on native immunoglobulin G complexes in early rheumatoid arthritis and its changes during therapy	CLINICAL AND EXPERIMENTAL IMMUNOLOGY												The goal of this study was to investigate the glycosylation profile of native immunoglobulin (Ig)G present in serum immune complexes in patients with rheumatoid arthritis (RA). To accomplish this, lectin binding assays, detecting the accessibility of glycans present on IgG-containing immune complexes by biotinylated lectins, were employed. Lectins capturing fucosyl residues (AAL), fucosylated tri-mannose N-glycan core sites (LCA), terminal sialic acid residues (SNA) and O-glycosidically linked galactose/N-acetylgalactosamine (GalNac-L) were used. Patients with recent-onset RA at baseline and after 3-year follow-up were investigated. We found that native IgG was complexed significantly more often with IgM, C1q, C3c and C-reactive protein (CRP) in RA patients, suggesting alterations of the native structure of IgG. The total accessibility of fucose residues on captured immune complexes to the respective lectin was significantly higher in patients with RA. Moreover, fucose accessibility on IgG-containing immune complexes correlated positively with the levels of antibodies to cyclic citrullinated peptides (anti-CCP). We also observed a significantly higher accessibility to sialic acid residues and galactose/GalNAc glyco-epitopes in native complexed IgG of patients with RA at baseline. While sialic acid accessibility increased during treatment, the accessibility of galactose/GalNAc decreased. Hence, successful treatment of RA was associated with an increase in the SNA/GalNAc-L ratio. Interestingly, the SNA/GalNAc-L ratio in particular rises after glucocorticoid treatment. In summary, this study shows the exposure of glycans in native complexed IgG of patients with early RA, revealing particular glycosylation patterns and its changes following pharmaceutical treatment.				Bilyy, Rostyslav/A-9777-2010; Sjoewall, Christoffer/C-9678-2009; Herrmann, Martin/A-9597-2013; Munoz, Luis E/E-7725-2010	Bilyy, Rostyslav/0000-0002-2344-1349; Sjoewall, Christoffer/0000-0003-0900-2048; Herrmann, Martin/0000-0002-0258-2484; Munoz, Luis E/0000-0002-5395-804X; Kastbom, Alf/0000-0001-7187-1477; Biermann, Mona/0000-0003-0496-5988												0009-9104	1365-2249				SEP	2017	189	3					372	382		10.1111/cei.12987							WOS:000407259700013	28509333					
J	Boulahneche, S; Jijie, R; Barras, A; Chekin, F; Singh, SK; Bouckaert, J; Medjram, MS; Kurungot, S; Boukherroub, R; Szunerits, S				Boulahneche, Samia; Jijie, Roxana; Barras, Alexandre; Chekin, Fereshteh; Singh, Santosh K.; Bouckaert, Julie; Medjram, Mohamed Salah; Kurungot, Sreekumar; Boukherroub, Rabah; Szunerits, Sabine			On demand electrochemical release of drugs from porous reduced graphene oxide modified flexible electrodes	JOURNAL OF MATERIALS CHEMISTRY B												Despite the advantages of an electrochemical control for drug release, only a handful of electrochemical-based release systems have been developed so far. We report herein on the development of an electrochemically activatable platform for on-demand delivery of drugs. It is based on flexible gold thin film electrodes coated with porous reduced graphene oxide (prGO) nanosheets onto which the drug of interest has been integrated beforehand. Two different drugs are investigated here: ondansetron hydrochloride (ODS), a selective 5-HT3 receptor antagonist used for preventing nausea and vomiting caused by chemotherapy and radiotherapy, and ampicillin (AMP), an antibiotic to prevent and treat a number of bacterial infections such as respiratory tract infections, urinary tract infections, and meningitis. In the case of ODS, application of a negative potential bias of -0.8 V results in a sustained slow ODS release with an ODS flux of 47 mu g cm(-2) h(-1). In the case of AMP, we show that polyethyleneimine modified prGO (prGO/PEI) is an extremely efficient matrix. Upon the application of +0.8 V, 24% of AMP could be released from the electrical interface in a time span of 2 h. The released AMP kept its antibacterial activity as demonstrated by antimicrobial tests. These examples illustrate the major benefits of the developed approach for biomedical applications.				; Kurungot, Sreekumar/M-6363-2013	Szunerits, Sabine/0000-0002-1567-4943; Kurungot, Sreekumar/0000-0001-5446-7923; singh, santosh/0000-0002-3210-3640												2050-750X	2050-7518				AUG 28	2017	5	32					6557	6565		10.1039/c7tb00687j							WOS:000407684800011						
J	Boeltz, S; Munoz, LE; Fuchs, TA; Herrmann, M				Boeltz, Sebastian; Munoz, Luis E.; Fuchs, Tobias A.; Herrmann, Martin			Neutrophil Extracellular Traps Open the Pandora's Box in Severe Malaria	FRONTIERS IN IMMUNOLOGY																Herrmann, Martin/A-9597-2013; Munoz, Luis E/E-7725-2010; Boeltz, Sebastian/H-3594-2014	Herrmann, Martin/0000-0002-0258-2484; Munoz, Luis E/0000-0002-5395-804X; Boeltz, Sebastian/0000-0001-5227-8707												1664-3224					JUL 28	2017	8								874	10.3389/fimmu.2017.00874							WOS:000406476300001	28804484					
J	Lehmer, C; Oeckl, P; Weishaupt, JH; Volk, AE; Diehl-Schmid, J; Schroeter, ML; Lauer, M; Kornhuber, J; Levin, J; Fassbender, K; Landwehrmeyer, B; Schludi, MH; Arzberger, T; Kremmer, E; Flatley, A; Feederle, R; Steinacker, P; Weydt, P; Ludolph, AC; Edbauer, D; Otto, M				Lehmer, Carina; Oeckl, Patrick; Weishaupt, Jochen H.; Volk, Alexander E.; Diehl-Schmid, Janine; Schroeter, Matthias L.; Lauer, Martin; Kornhuber, Johannes; Levin, Johannes; Fassbender, Klaus; Landwehrmeyer, Bernhard; Schludi, Martin H.; Arzberger, Thomas; Kremmer, Elisabeth; Flatley, Andrew; Feederle, Regina; Steinacker, Petra; Weydt, Patrick; Ludolph, Albert C.; Edbauer, Dieter; Otto, Markus		German Consortium Frontotemporal L	Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD	EMBO MOLECULAR MEDICINE												The C9orf72 GGGGCC repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). Non-conventional repeat translation results in five dipeptide repeat proteins (DPRs), but their clinical utility, overall significance, and temporal course in the pathogenesis of c9ALS/FTD are unclear, although animal models support a gain-of-function mechanism. Here, we established a poly-GP immunoassay from cerebrospinal fluid (CSF) to identify and characterize C9orf72 patients. Significant poly-GP levels were already detectable in asymptomatic C9orf72 mutation carriers compared to healthy controls and patients with other neurodegenerative diseases. The poly-GP levels in asymptomatic carriers were similar to symptomatic c9ALS/FTD cases. Poly-GP levels were not correlated with disease onset, clinical scores, and CSF levels of neurofilaments as a marker for axonal damage. Poly-GP determination in CSF revealed a C9orf72 mutation carrier in our cohort and may thus be used as a diagnostic marker in addition to genetic testing to screen patients. Presymptomatic expression of poly-GP and likely other DPR species may contribute to disease onset and thus represents an alluring therapeutic target.				Edbauer, Dieter/M-9906-2019; Otto, Markus/F-4304-2015; Levin, Johannes/E-4052-2010; Jahn, Holger/A-9255-2008; Danek, Adrian/G-7339-2011; Ziegler, Georg C/N-8985-2015; Levin, Johannes/W-8686-2019; Kornhuber, Johannes/B-9613-2014	Edbauer, Dieter/0000-0002-7186-4653; Otto, Markus/0000-0003-4273-4267; Levin, Johannes/0000-0001-5092-4306; Jahn, Holger/0000-0003-3607-7651; Danek, Adrian/0000-0001-8857-5383; Ziegler, Georg C/0000-0001-9411-3169; Levin, Johannes/0000-0001-5092-4306; Kornhuber, Johannes/0000-0002-8096-3987; Fassbender, Klaus/0000-0003-3596-868X; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X; Oeckl, Patrick/0000-0002-7652-7023; Diehl-Schmid, Janine/0000-0002-7745-1382												1757-4676	1757-4684				JUL	2017	9	7					859	868		10.15252/emmm.201607486							WOS:000404552000003	28408402					
J	Tranchard, P; Duquesne, S; Samyn, F; Estebe, B; Bourbigot, S				Tranchard, Pauline; Duquesne, Sophie; Samyn, Fabienne; Estebe, Bruno; Bourbigot, Serge			Kinetic analysis of the thermal decomposition of a carbon fibre-reinforced epoxy resin laminate	JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS												Kinetic decomposition model of a carbon-reinforced epoxy laminate (T700/M21 composite) applied to aircraft structures were determined from specific techniques. Data obtained from the thermogravimetric (TG) experiment coupled with Fourier Transform Infrared (FTIR) spectrometer and combined with the NETZSCH Thermokinetics numerical tool were used to determine a comprehensive kinetic model. Experimental and numerical approaches were thus coupled to determine the decomposition mechanism of a partially unknown composite (T700/M21). Using Thermokinetics, a multi-step reactions kinetic model was established based on the TG and differential thermogravimetric (DTG) results. It is composed of two main competitive reaction, e.g. n(th) order and autocatalytic reactions). New approach combining TG-FTIR-Thermokinetics is proposed to make kinetic analysis of complex carbon fibre reinforced epoxy composite (mixture of epoxy resins blended with different thermoplastic polymers).					Tranchard, Pauline/0000-0002-9253-3140												0165-2370	1873-250X				JUL	2017	126						14	21		10.1016/j.jaap.2017.07.002							WOS:000407984300002						
J	Ramgobin, A; Fontaine, G; Penverne, C; Bourbigot, S				Ramgobin, Aditya; Fontaine, Gaelle; Penverne, Christophe; Bourbigot, Serge			Thermal Stability and Fire Properties of Salen and Metallosalens as Fire Retardants in Thermoplastic Polyurethane (TPU)	MATERIALS												This study deals with the synthesis and evaluation of salen based derivatives as fire retardants in thermoplastic polyurethane. Salens, hydroxysalens and their first row transition metal complexes (salen-M) were synthesized (Copper, Manganese, Nickel and Zinc). They were then incorporated in thermoplastic polyurethane (TPU) with a loading as low as 10:1 weight ratio. The thermal stability as well as the fire properties of the formulations were evaluated. Thermogravimetric analysis (TGA) showed that different coordination metals on the salen could induce different decomposition pathways when mixed with TPU. The Pyrolysis Combustion Flow Calorimetry (PCFC) results showed that some M-salen have the ability to significantly decrease the peak heat release rate (-61% compared to neat TPU) and total heat released (-63% compared to neat TPU) when formulated at 10:1 wt % ratio in TPU. Mass Loss Cone Calorimetry (MLC) results have shown that some additives (salen-Cu and salen-Mn) exhibit very promising performance and they are good candidates as flame-retardants for TPU.					Bourbigot, Serge/0000-0003-1536-2015; Gaelle, Fontaine/0000-0002-7113-1687; Penverne, Christophe/0000-0002-6629-6129													1996-1944				JUN	2017	10	6							665	10.3390/ma10060665							WOS:000404415000099	28773025					
J	Dubois-Chevalier, J; Dubois, V; Dehondt, H; Mazrooei, P; Mazuy, C; Serandour, AA; Gheeraert, C; Guillaume, P; Bauge, E; Derudas, B; Hennuyer, N; Paumelle, R; Marot, G; Carroll, JS; Lupien, M; Staels, B; Lefebvre, P; Eeckhoute, J				Dubois-Chevalier, Julie; Dubois, Vanessa; Dehondt, Helene; Mazrooei, Parisa; Mazuy, Claire; Serandour, Aurelien A.; Gheeraert, Celine; Guillaume, Penderia; Bauge, Eric; Derudas, Bruno; Hennuyer, Nathalie; Paumelle, Rejane; Marot, Guillemette; Carroll, Jason S.; Lupien, Mathieu; Staels, Bart; Lefebvre, Philippe; Eeckhoute, Jerome			The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions	GENOME RESEARCH												Control of gene transcription relies on concomitant regulation by multiple transcriptional regulators (TRs). However, how recruitment of a myriad of TRs is orchestrated at cis-regulatory modules (CRMs) to account for coregulation of specific biological pathways is only partially understood. Here, we have used mouse liver CRMs involved in regulatory activities of the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system to tackle this question. Using integrative cistromic, epigenomic, transcriptomic, and interactomic analyses, we reveal a logical organization where trans-regulatory modules (TRMs), which consist of subsets of preferentially and coordinately corecruited TRs, assemble into hierarchical combinations at hepatic CRMs. Different combinations of TRMs add to a core TRM, broadly found across the whole landscape of CRMs, to discriminate promoters from enhancers. These combinations also specify distinct sets of CRM differentially organized along the genome and involved in regulation of either housekeeping/cellular maintenance genes or liverspecific functions. In addition to these TRMs which we define as obligatory, we show that facultative TRMs, such as one comprising core circadian TRs, are further recruited to selective subsets of CRMs to modulate their activities. TRMs transcend TR classification into ubiquitous versus liver-identity factors, as well as TR grouping into functional families. Hence, hierarchical superimpositions of obligatory and facultative TRMs bring about independent transcriptional regulatory inputs defining different sets of CRMs with logical connection to regulation of specific gene sets and biological pathways. Altogether, our study reveals novel principles of concerted transcriptional regulation by multiple TRs at CRMs.				Staels, Bart/N-9497-2016; Lefebvre, Philippe/F-2685-2010; Paumelle, Rejane/R-6675-2018; Bauge, Eric/R-6522-2018	Staels, Bart/0000-0002-3784-1503; Lefebvre, Philippe/0000-0002-9366-5129; Paumelle, Rejane/0000-0002-4489-0717; Eeckhoute, Jerome/0000-0002-7222-9264; Carroll, Jason/0000-0003-3643-0080; Dubois, Vanessa/0000-0001-8894-2980; Bauge, Eric/0000-0001-9994-8667; Dubois-Chevalier, Julie/0000-0003-0471-752X; HENNUYER, Nathalie/0000-0003-0303-7258; Dehondt, Helene/0000-0003-2900-4673												1088-9051	1549-5469				JUN	2017	27	6					985	996		10.1101/gr.217075.116							WOS:000402521400009	28400425					
J	Lasalle, M; Hoguet, V; Hennuyer, N; Leroux, F; Piveteau, C; Belloy, L; Lestavel, S; Vallez, E; Dorchies, E; Duplan, I; Sevin, E; Culot, M; Gosselet, F; Boulahjar, R; Herledan, A; Staels, B; Deprez, B; Tailleux, A; Charton, J				Lasalle, Manuel; Hoguet, Vanessa; Hennuyer, Nathalie; Leroux, Florence; Piveteau, Catherine; Belloy, Loic; Lestavel, Sophie; Vallez, Emmanuelle; Dorchies, Emilie; Duplan, Isabelle; Sevin, Emmanuel; Culot, Maxime; Gosselet, Fabien; Boulahjar, Rajaa; Herledan, Adrien; Staels, Bart; Deprez, Benoit; Tailleux, Anne; Charton, Julie			Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose Tolerance	JOURNAL OF MEDICINAL CHEMISTRY												The role of the G-protein-coupled bile acid receptor TGRS in various organs, tissues, and cell types; specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGRS agonists. To avoid these. systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGRS agonists with low intestinal petmeability. In this article, we describe their synthesis, characterization, and biological evaluation. Among them, compound 24 is a potent GLP-1 secretagogue, has low effect on gallbladder volume, and improves glucose homeostasis in a preclinical murine model of diet-induced obesity and insulin resistance, making the proof of concept of the potential of topical intestinal TGR5 agonists as therapeutic agents in type-2 diabetes.				Lestavel, Sophie/B-4658-2017; Staels, Bart/N-9497-2016; Charton, Julie/U-4603-2018; Gosselet, Fabien/U-8427-2019; deprez, benoit/G-6749-2012; TAILLEUX, Anne/R-5530-2018	Lestavel, Sophie/0000-0001-7839-4757; Staels, Bart/0000-0002-3784-1503; Charton, Julie/0000-0001-6895-276X; Gosselet, Fabien/0000-0002-0481-5026; deprez, benoit/0000-0002-2777-4538; HENNUYER, Nathalie/0000-0003-0303-7258; TAILLEUX, Anne/0000-0003-1430-2627												0022-2623	1520-4804				MAY 25	2017	60	10					4185	4211		10.1021/acs.jmedchem.6b01873							WOS:000402498200007	28414465					
J	Chavez-Talavera, O; Tailleux, A; Lefebvre, P; Staels, B				Chavez-Talavera, Oscar; Tailleux, Anne; Lefebvre, Philippe; Staels, Bart			Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease	GASTROENTEROLOGY												Bile acids are signaling molecules that coordinately regulate metabolism and inflammation via the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in bile acid, lipid and carbohydrate metabolism, energy expenditure, and inflammation by acting predominantly in enterohepatic tissues, but also in peripheral organs. In this review, we discuss the most recent findings on the inter-organ signaling and interplay with the gut microbiota of bile acids and their receptors in meta-inflammation, with a focus on their pathophysiologic roles in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic steatohepatitis, and their potential therapeutic applications.				Lefebvre, Philippe/F-2685-2010; Staels, Bart/N-9497-2016; TAILLEUX, Anne/R-5530-2018	Lefebvre, Philippe/0000-0002-9366-5129; Staels, Bart/0000-0002-3784-1503; TAILLEUX, Anne/0000-0003-1430-2627												0016-5085	1528-0012				MAY	2017	152	7			SI		1679	+		10.1053/j.gastro.2017.01.055							WOS:000401812000006	28214524					
J	Sarazin, J; Bachelet, P; Bourbigot, S				Sarazin, Johan; Bachelet, Pierre; Bourbigot, Serge			Fire behavior of simulated low voltage intumescent cables with and without electric current	JOURNAL OF FIRE SCIENCES												Many circumstances can lead to an electrical fire. It is then helpful to reproduce those circumstances in laboratory conditions to duplicate fire scenarios in order to increase knowledge and to develop safer and flame-retarded materials and electrical systems. Our approach was to develop specific bench scale tests. The mass loss cone calorimeter coupled with Fourier transform infrared was used to mimic a fire scenario on simulated low voltage cable (flame-retarded polymer molded around copper wire) and to characterize the gas phase. The electric current creates an additional heating condition (Joule effect) which can modify the decomposition of the flammable material (e.g. the cable jacket made in thermoplastic), and so its fire behavior in case of fire. It is the reason why we performed the experiments mimicking different fire scenarios with and without electric current. Specific test was also developed to investigate the flame spread and the delamination of the polymer around the wire. The bench scale tests presented in this article were applied on intumescent polymers (ethylene-vinyl acetate containing commercial intumescent additive). The results were discussed with a special emphasis on the influence of electric current on the fire behavior.																	0734-9041	1530-8049				MAY	2017	35	3					179	194		10.1177/0734904117698843							WOS:000400736500001						
J	Tranchard, P; Samyn, F; Duquesne, S; Estebe, B; Bourbigot, S				Tranchard, Pauline; Samyn, Fabienne; Duquesne, Sophie; Estebe, Bruno; Bourbigot, Serge			Modelling Behaviour of a Carbon Epoxy Composite Exposed to Fire: Part II-Comparison with Experimental Results	MATERIALS												Based on a phenomenological methodology, a three dimensional (3D) thermochemical model was developed to predict the temperature profile, the mass loss and the decomposition front of a carbon-reinforced epoxy composite laminate (T700/M21 composite) exposed to fire conditions. This 3D model takes into account the energy accumulation by the solid material, the anisotropic heat conduction, the thermal decomposition of the material, the gas mass flow into the composite, and the internal pressure. Thermophysical properties defined as temperature dependant properties were characterised using existing as well as innovative methodologies in order to use them as inputs into our physical model. The 3D thermochemical model accurately predicts the measured mass loss and observed decomposition front when the carbon fibre/epoxy composite is directly impacted by a propane flame. In short, the model shows its capability to predict the fire behaviour of a carbon fibre reinforced composite for fire safety engineering.					Bourbigot, Serge/0000-0003-1536-2015; Tranchard, Pauline/0000-0002-9253-3140												1996-1944					MAY	2017	10	5							470	10.3390/ma10050470							WOS:000404411000022	28772836					
J	Tranchard, P; Samyn, F; Duquesne, S; Estebe, B; Bourbigot, S				Tranchard, Pauline; Samyn, Fabienne; Duquesne, Sophie; Estebe, Bruno; Bourbigot, Serge			Modelling Behaviour of a Carbon Epoxy Composite Exposed to Fire: Part I-Characterisation of Thermophysical Properties	MATERIALS												Thermophysical properties of a carbon-reinforced epoxy composite laminate (T700/M21 composite for aircraft structures) were evaluated using different innovative characterisation methods. Thermogravimetric Analysis (TGA), Simultaneous Thermal analysis (STA), Laser Flash analysis (LFA), and Fourier Transform Infrared (FTIR) analysis were used for measuring the thermal decomposition, the specific heat capacity, the anisotropic thermal conductivity of the composite, the heats of decomposition and the specific heat capacity of released gases. It permits to get input data to feed a three-dimensional (3D) model given the temperature profile and the mass loss obtained during well-defined fire scenarios (model presented in Part II of this paper). The measurements were optimised to get accurate data. The data also permit to create a public database on an aeronautical carbon fibre/epoxy composite for fire safety engineering.					Bourbigot, Serge/0000-0003-1536-2015; Tranchard, Pauline/0000-0002-9253-3140												1996-1944					MAY	2017	10	5							494	10.3390/ma10050494							WOS:000404411000046	28772854					
J	Chen, J; Chaurio, RA; Maueroder, C; Derer, A; Rauh, M; Kost, A; Liu, Y; Mo, XM; Hueber, A; Bilyy, R; Herrmann, M; Zhao, Y; Munoz, LE				Chen, Jin; Chaurio, Ricardo A.; Maueroeder, Christian; Derer, Anja; Rauh, Manfred; Kost, Andriy; Liu, Yi; Mo, Xianming; Hueber, Axel; Bilyy, Rostyslav; Herrmann, Martin; Zhao, Yi; Munoz, Luis E.			Inosine Released from Dying or Dead Cells Stimulates Cell Proliferation via Adenosine Receptors	FRONTIERS IN IMMUNOLOGY												Introduction: Many antitumor therapies induce apoptotic cell death in order to cause tumor regression. Paradoxically, apoptotic cells are also known to promote wound healing, cell proliferation, and tumor cell repopulation in multicellular organisms. We aimed to characterize the nature of the regenerative signals concentrated in the micromilieu of dead and dying cells. Methods: Cultures of viable melanoma B16F10 cells, mouse fibroblasts, and primary human fibroblast-like synoviocytes (FLS) in the presence of dead and dying cells, their supernatants (SNs), or purified agonists and antagonists were used to evaluate the stimulation of proliferation. Viable cell quantification was performed by either flow cytometry of harvested cells or by crystal violet staining of adherent cells. High-performance liquid chromatography and liquid chromatography coupled with mass spectrometry of cell SNs were deployed to identify the nature of growth-promoting factors. Coimplantation of living cells in the presence of SNs collected from dead and dying cells and specific agonists was used to evaluate tumor growth in vivo. Results: The stimulation of proliferation of few surviving cells by bystander dead cells was confirmed for melanoma cells, mouse fibroblasts, and primary FLS. We found that small soluble molecules present in the protein-free fraction of SNs of dead and dying cells were responsible for the promotion of proliferation. The nucleoside inosine released by dead and dying cells acting via adenosine receptors was identified as putative inducer of proliferation of surviving tumor cells after irradiation and heat treatment. Conclusion: Inosine released by dead and dying cells mediates tumor cell proliferation via purinergic receptors. Therapeutic strategies surmounting this pathway may help to reduce the rate of recurrence after radio- and chemotherapy.				Munoz, Luis E/E-7725-2010; Bilyy, Rostyslav/A-9777-2010; Herrmann, Martin/A-9597-2013; Maueroder, Christian/H-7412-2016; Kost, Andriy/L-2336-2018	Munoz, Luis E/0000-0002-5395-804X; Bilyy, Rostyslav/0000-0002-2344-1349; Herrmann, Martin/0000-0002-0258-2484; Maueroder, Christian/0000-0002-7563-883X; Kost, Andriy/0000-0001-7401-7460												1664-3224					APR 27	2017	8								504	10.3389/fimmu.2017.00504							WOS:000400316100001	28496447					
J	Simonsen, AH; Herukka, SK; Andreasen, N; Baldeiras, I; Bjerke, M; Blennow, K; Engelborghs, S; Frisoni, GB; Gabryelewicz, T; Galluzzi, S; Handels, R; Kramberger, MG; Kulczynska, A; Molinuevo, JL; Mroczko, B; Nordberg, A; Oliveira, CR; Otto, M; Rinne, JO; Rot, U; Saka, E; Soininen, H; Struyfs, H; Suardi, S; Visser, PJ; Winblad, B; Zetterberg, H; Waldemar, G				Simonsen, Anja Hviid; Herukka, Sanna-Kaisa; Andreasen, Niels; Baldeiras, Ines; Bjerke, Maria; Blennow, Kaj; Engelborghs, Sebastiaan; Frisoni, Giovanni B.; Gabryelewicz, Tomasz; Galluzzi, Samantha; Handels, Ron; Kramberger, Milica G.; Kulczynska, Agnieszka; Luis Molinuevo, Jose; Mroczko, Barbara; Nordberg, Agneta; Oliveira, Catarina Resende; Otto, Markus; Rinne, Juha O.; Rot, Uros; Saka, Esen; Soininen, Hilkka; Struyfs, Hanne; Suardi, Silvia; Visser, Pieter Jelle; Winblad, Bengt; Zetterberg, Henrik; Waldemar, Gunhild			Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia	ALZHEIMERS & DEMENTIA												This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebiospinal fluid (CSF) amyloid-beta(1-42), tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results. The working group found sufficient evidence to support 4 recommendation to use CSF ADbiomarkers as a supplement to clinical evaluation, particularly in uncertain and atypical cases, to identify or exclude AD as the cause of dementia. Because of insufficient evidence, it was uncertain whether CSF AD bioniarkers outperform imaging biomarkers. Operational recommendations for the interpretation of ambiguous CSF biomarker results were also provided. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.				Mroczko, Barbara/R-5955-2018; Otto, Markus/F-4304-2015; Visser, Pieter J/C-8541-2015; Visser, Pieter Jelle/S-5242-2019; Galluzzi, Samantha/K-5218-2016	Mroczko, Barbara/0000-0002-4075-8479; Otto, Markus/0000-0003-4273-4267; Visser, Pieter J/0000-0001-8008-9727; Visser, Pieter Jelle/0000-0001-8008-9727; Simonsen, Anja Hviid/0000-0002-5461-162X; Baldeiras, Ines/0000-0002-8106-7308; Galluzzi, Samantha/0000-0001-9804-5669; Handels, Ron/0000-0002-8663-0630; Molinuevo, Jose Luis/0000-0003-0485-6001; Oliveira, Catarina/0000-0001-6942-4328; Nordberg, Agneta/0000-0001-7345-5151												1552-5260	1552-5279				MAR	2017	13	3					274	284		10.1016/j.jalz.2016.09.008							WOS:000395968200009	28341065					
J	Herukka, SK; Simonsen, AH; Andreasen, N; Baldeiras, I; Bjerke, M; Blennow, K; Engelborghs, S; Frisoni, GB; Gabryelewicz, T; Galluzzi, S; Handels, R; Kramberger, MG; Kulczynska, A; Molinuevo, JL; Mroczko, B; Nordberg, A; Oliveira, CR; Otto, M; Rinne, JO; Rot, U; Saka, E; Soininen, H; Struyfs, H; Suardi, S; Visser, PJ; Winblad, B; Zetterberg, H; Waldemar, G				Herukka, Sanna-Kaisa; Simonsen, Anja Hviid; Andreasen, Niels; Baldeiras, Ines; Bjerke, Maria; Blennow, Kaj; Engelborghs, Sebastiaan; Frisoni, Giovanni B.; Gabryelewicz, Tomasz; Galluzzi, Samantha; Handels, Ron; Kramberger, Milica G.; Kulczynska, Agnieszka; Luis Molinuevo, Jose; Mroczko, Barbara; Nordberg, Agneta; Oliveira, Catarina Resende; Otto, Markus; Rinne, Juha O.; Rot, Uros; Saka, Esen; Soininen, Hilkka; Struyfs, Hanne; Suardi, Silvia; Visser, Pieter Jelle; Winblad, Bengt; Zetterberg, Henrik; Waldemar, Gunhild			Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment	ALZHEIMERS & DEMENTIA												This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-beta(1-42), tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3)interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre-and post-biomarker counseling. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.				Otto, Markus/F-4304-2015; Mroczko, Barbara/R-5955-2018; Visser, Pieter Jelle/S-5242-2019; Visser, Pieter J/C-8541-2015; Galluzzi, Samantha/K-5218-2016	Otto, Markus/0000-0003-4273-4267; Mroczko, Barbara/0000-0002-4075-8479; Visser, Pieter Jelle/0000-0001-8008-9727; Visser, Pieter J/0000-0001-8008-9727; Handels, Ron/0000-0002-8663-0630; Galluzzi, Samantha/0000-0001-9804-5669; Baldeiras, Ines/0000-0002-8106-7308; Nordberg, Agneta/0000-0001-7345-5151; Oliveira, Catarina/0000-0001-6942-4328; Simonsen, Anja Hviid/0000-0002-5461-162X; Molinuevo, Jose Luis/0000-0003-0485-6001												1552-5260	1552-5279				MAR	2017	13	3					285	295		10.1016/j.jalz.2016.09.009							WOS:000395968200010	28341066					
J	Teodorescu, F; Oz, Y; Queniat, G; Abderrahmani, A; Foulon, C; Lecoeur, M; Sanyal, R; Sanyal, A; Boukherroub, R; Szunerits, S				Teodorescu, Florina; Oz, Yavuz; Queniat, Gurvan; Abderrahmani, Amar; Foulon, Catherine; Lecoeur, Marie; Sanyal, Rana; Sanyal, Amitav; Boukherroub, Rabah; Szunerits, Sabine			Photothermally triggered on-demand insulin release from reduced graphene oxide modified hydrogels	JOURNAL OF CONTROLLED RELEASE												On-demand delivery of therapeutics plays an essential role in simplifying and improving patient care. The high loading capacity of reduced graphene oxide (rGO) for drugs has made this matrix of particular interest for its hybridization with therapeutics. In this work, we describe the formulation of rGO impregnated poly(ethylene glycol) dimethacrylate based hydrogels (PEGDMA-rGO) and their efficient loading with insulin. Near-infrared (NIR) light induced heating of the PEGDMA-rGO hydrogels allows for highly efficient insulin release. Most importantly, we validate that the NIR irradiation of the hydrogel has no effect on the biological and metabolic activities of the released insulin. The ease of insulin loading/reloading makes this photothermally triggered release strategy of interest for diabetic patients. Additionally, the rGO-based protein releasing platform fabricated here can be expanded towards 'on demand' release of various other therapeutically relevant biomolecules. (C) 2016 Elsevier B.V. All rights reserved.				Abderrahmani, Amar/O-3124-2017; /I-4328-2013; Boukherroub, Rabah/I-4826-2017	Abderrahmani, Amar/0000-0003-0752-0343; /0000-0001-5122-8329; Szunerits, Sabine/0000-0002-1567-4943; Boukherroub, Rabah/0000-0002-9795-9888; SANYAL, RANA/0000-0003-4803-5811; TEODORESCU, Florina/0000-0003-2167-0962												0168-3659	1873-4995				JAN 28	2017	246						164	173		10.1016/j.jconrel.2016.10.028							WOS:000396475500016	27984105					
J	Teodorescu, F; Queniat, G; Foulon, C; Lecoeur, M; Barras, A; Boulahneche, S; Medjram, MS; Hubert, T; Abderrahmani, A; Boukherroub, R; Szunerits, S				Teodorescu, Florina; Queniat, Gurvan; Foulon, Catherine; Lecoeur, Marie; Barras, Alexandre; Boulahneche, Samia; Medjram, Mohmaed Salah; Hubert, Thomas; Abderrahmani, Amar; Boukherroub, Rabah; Szunerits, Sabine			Transdermal skin patch based on reduced graphene oxide: A new approach for photothermal triggered permeation of ondansetron across porcine skin	JOURNAL OF CONTROLLED RELEASE												The development of a skin-mounted patch capable of controlled transcutaneous delivery of therapeutics through thermal activation provides a unique solution for the controlled release of active principles over long-term periods. Here, we report on a flexible transdermal patch for photothermal triggered release of ondansetron (ODS), a commonly used drug for the treatment of chemotherapy-induced nausea and vomiting and used as model compound here. To achieve this, a dispersion of ODS-loaded reduced graphene oxide (rGO-ODS) nanosheets were deposited onto Kapton to produce a flexible polyimide-based patch. It is demonstrated that ODS loaded Kapton/rGO patches have a high drug delivery performance upon irradiation with a continuous laser beam at 980 nm for 10 min due to an induced photothermal heating effect. The ability of ODS impregnated Kapton/rGO patches as transdermal delivery scaffolds for ODS across the skin is in addition investigated using porcine ear skin as a model. We show that the cumulative quantity and flux of ODS passing the skin are highly depending on the laser power density used. At 5 W cm(-2) irradiation, the ODS flux across pig skin was determined to be 1.6 mu g cm(-2) h(-1) comparable to other approaches. The use of tween 20 as skin enhancer could significantly increase the ODS flux to 13.2 mu g cm(-2) h(-1). While the skin penetration enhancement is comparable to that obtained using otherwell-known permeation enhancers, the actual superiority and interest of the proposed approach is that the Kapton/rGO photoactivatable skin patch can be loaded with any drugs and therapeutics of interest, making the approach extremely versatile. The on demand delivery of drugs upon local laser irradiation and the possibility to reload the interface with the drug makes this new drug administration route very appealing. (C) 2016 Elsevier B.V. All rights reserved.				Abderrahmani, Amar/O-3124-2017; Boukherroub, Rabah/I-4826-2017	Abderrahmani, Amar/0000-0003-0752-0343; Szunerits, Sabine/0000-0002-1567-4943; Boukherroub, Rabah/0000-0002-9795-9888; TEODORESCU, Florina/0000-0003-2167-0962												0168-3659	1873-4995				JAN 10	2017	245						137	146		10.1016/j.jconrel.2016.11.029							WOS:000396474500013	27914995					
J	Maueroder, C; Mahajan, A; Paulus, S; Gosswein, S; Hahn, J; Kienhofer, D; Biermann, MH; Tripal, P; Friedrich, RP; Munoz, LE; Neurath, MF; Becker, C; Schett, GA; Herrmann, M; Leppkes, M				Maueroeder, Christian; Mahajan, Aparna; Paulus, Susanne; Goesswein, Stefanie; Hahn, Jonas; Kienhoefer, Deborah; Biermann, Mona H.; Tripal, Philipp; Friedrich, Ralf P.; Munoz, Luis E.; Neurath, Markus F.; Becker, Christoph; Schett, Georg Andreas; Herrmann, Martin; Leppkes, Moritz			Menage-a-Trois: The Ratio of Bicarbonate to CO2 and the pH Regulate the Capacity of Neutrophils to Form NETs	FRONTIERS IN IMMUNOLOGY												In this study, we identified and characterized the potential of a high ratio of bicarbonate to CO2 and a moderately alkaline pH to render neutrophils prone to undergo neutrophil extracellular trap (NET) formation. Both experimental settings increased the rate of spontaneous NET release and potentiated the NET-inducing capacity of phorbol esters (phorbol-2-myristate-13-acetate), ionomycin, monosodium urate, and LPS. In contrast, an acidic environment impaired NET formation both spontaneous and induced. Our findings indicate that intracellular alkalinization of neutrophils in response to an alkaline environment leads to an increase of intracellular calcium and neutrophil activation. We further found that the anion channel blocker DIDS strongly reduced NET formation induced by bicarbonate. This finding suggests that the effects observed are due to a molecular program that renders neutrophils susceptible to NET formation. Inflammatory foci may be characterized by an acidic environment. Our data indicate that NET formation is favored by the higher pH at the border regions of inflamed areas. Moreover, our findings highlight the necessity for strict pH control during assays of NET formation.				Munoz, Luis E/E-7725-2010; Leppkes, Moritz/N-2932-2017; Herrmann, Martin/A-9597-2013; Maueroder, Christian/H-7412-2016	Munoz, Luis E/0000-0002-5395-804X; Herrmann, Martin/0000-0002-0258-2484; Hahn, Jonas/0000-0003-3944-2108; Maueroder, Christian/0000-0002-7563-883X; Biermann, Mona/0000-0003-0496-5988												1664-3224					DEC 9	2016	7								583	10.3389/fimmu.2016.00583							WOS:000389854900001	28018350					
J	Biermann, MHC; Podolska, MJ; Knopf, J; Reinwald, C; Weidner, D; Maueroder, C; Hahn, J; Kienhofer, D; Barras, A; Boukherroub, R; Szunerits, S; Bilyy, R; Hoffmann, M; Zhao, Y; Schett, G; Herrmann, M; Munoz, LE				Biermann, Mona H. C.; Podolska, Malgorzata J.; Knopf, Jasmin; Reinwald, Christiane; Weidner, Daniela; Maueroeder, Christian; Hahn, Jonas; Kienhoefer, Deborah; Barras, Alexandre; Boukherroub, Rabah; Szunerits, Sabine; Bilyy, Rostyslav; Hoffmann, Markus; Zhao, Yi; Schett, Georg; Herrmann, Martin; Munoz, Luis E.			Oxidative Burst-Dependent NETosisis Is Implicated in the Resolution of Necrosis-Associated Sterile Inflammation	FRONTIERS IN IMMUNOLOGY												Necrosis is associated with a profound inflammatory response. The regulation of necrosis-associated inflammation, particularly the mechanisms responsible for resolution of inflammation is incompletely characterized. Nanoparticles are known to induce plasma membrane damage and necrosis followed by sterile inflammation. We observed that injection of metabolically inert nanodiamonds resulted in paw edema in WT and Ncf1** mice. However, while inflammation quickly resolved in WT mice, it persisted over several weeks in Ncf1** mice indicating failure of resolution of inflammation. Mechanistically, NOX2-dependent reactive oxygen species (ROS) production and formation of neutrophil extracellular traps were essential for the resolution of necrosis-induced inflammation: hence, by evaluating the fate of the particles at the site of inflammation, we observed that Ncf1** mice deficient in NADPH-dependent ROS failed to generate granulation tissue therefore being unable to trap the nanodiamonds. These data suggest that NOX2-dependent NETosis is crucial for preventing the chronification of the inflammatory response to tissue necrosis by forming NETosis-dependent barriers between the necrotic and healthy surrounding tissue.				Herrmann, Martin/A-9597-2013; Bilyy, Rostyslav/A-9777-2010; Munoz, Luis E/E-7725-2010; Maueroder, Christian/H-7412-2016; Boukherroub, Rabah/I-4826-2017	Herrmann, Martin/0000-0002-0258-2484; Bilyy, Rostyslav/0000-0002-2344-1349; Munoz, Luis E/0000-0002-5395-804X; Maueroder, Christian/0000-0002-7563-883X; Biermann, Mona/0000-0003-0496-5988; Boukherroub, Rabah/0000-0002-9795-9888; Hahn, Jonas/0000-0003-3944-2108; Szunerits, Sabine/0000-0002-1567-4943; Hoffmann, Markus/0000-0001-9698-9922												1664-3224					DEC 1	2016	7								557	10.3389/fimmu.2016.00557							WOS:000388960100001	27990145					
J	Szunerits, S; Boukherroub, R				Szunerits, Sabine; Boukherroub, Rabah			Antibacterial activity of graphene-based materials	JOURNAL OF MATERIALS CHEMISTRY B												Complications related to infectious diseases have significantly decreased due to the availability and use of a wide variety of antibiotics and antimicrobial agents. However, excessive use of antibiotics and antimicrobial agents over years has increased the number of drug resistant pathogens. Microbial multidrug resistance poses serious risks and consequently research attention has refocused on finding alternatives for antimicrobial treatment. Among the various approaches, the use of engineered nanostructures is currently the most promising strategy to overcome microbial drug resistance by improving the remedial efficiency due to their high surface-to-volume ratio and their intrinsic or chemically incorporated antibacterial activity. Graphene, a two-dimensional ultra-thin nanomaterial, possesses excellent biocompatibility, putting it in the forefront for different applications in biosensing, drug delivery, biomedical device development, diagnostics and therapeutics. Graphene-based nanostructures also hold great promise for combating microbial infections. Yet, several questions remain unanswered such as the mechanism of action with the microbial entities, the importance of size and chemical composition in the inhibition of bacterial proliferation and adhesion, cytotoxicity, and other issues when considering future clinical implementation. This review summarizes the current efforts in the formulation of graphene-based nanocomposites with antimicrobial and antibiofilm activities as new tools to tackle the current challenges in fighting against bacterial targets. Furthermore, the review describes the features of graphene-bacterial interactions, with the hope to shed light on the range of possible mode of actions, serving the goal to develop a better understanding of the antibacterial capabilities of graphene-based nanostructures.				Boukherroub, Rabah/I-4826-2017	Boukherroub, Rabah/0000-0002-9795-9888; Szunerits, Sabine/0000-0002-1567-4943												2050-750X	2050-7518				NOV 21	2016	4	43					6892	6912		10.1039/c6tb01647b							WOS:000387882000001						
J	Munoz, LE; Bilyy, R; Biermann, MHC; Kienhofer, D; Maueroder, C; Hahn, J; Brauner, JM; Weidner, D; Chen, J; Scharin-Mehlmann, M; Janko, C; Friedrich, RP; Mielenz, D; Dumych, T; Lootsik, MD; Schauer, C; Schett, G; Hoffmann, M; Zhao, Y; Herrmann, M				Munoz, Luis E.; Bilyy, Rostyslav; Biermann, Mona H. C.; Kienhoefer, Deborah; Maueroeder, Christian; Hahn, Jonas; Brauner, Jan M.; Weidner, Daniela; Chen, Jin; Scharin-Mehlmann, Marina; Janko, Christina; Friedrich, Ralf P.; Mielenz, Dirk; Dumych, Tetiana; Lootsik, Maxim D.; Schauer, Christine; Schett, Georg; Hoffmann, Markus; Zhao, Yi; Herrmann, Martin			Nanoparticles size-dependently initiate self-limiting NETosis-driven inflammation	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA												The critical size for strong interaction of hydrophobic particles with phospholipid bilayers has been predicted to be 10 nm. Because of the wide spreading of nonpolar nanoparticles (NPs) in the environment, we aimed to reveal the ability of living organisms to entrap NPs via formation of neutrophil extracellular traps (NETs). Upon interaction with various cell types and tissues, 10-to 40-nm-sized NPs induce fast (<20 min) damage of plasma membranes and instability of the lysosomal compartment, leading to the immediate formation of NETs. In contrast, particles sized 100-1,000 nm behaved rather inertly. Resulting NET formation (NETosis) was accompanied by an inflammatory reaction intrinsically endowed with its own resolution, demonstrated in lungs and air pouches of mice. Persistence of small NPs in joints caused unremitting arthritis and bone remodeling. Small NPs coinjected with antigen exerted adjuvant-like activity. This report demonstrates a cellularmechanism that explains how small NPs activate the NETosis pathway and drive their entrapping and resolution of the initial inflammatory response.				Herrmann, Martin/A-9597-2013; Dumych, Tetiana/H-9450-2018; Friedrich, Ralf/R-2580-2016; Maueroder, Christian/H-7412-2016; Bilyy, Rostyslav/A-9777-2010; Munoz, Luis E/E-7725-2010	Herrmann, Martin/0000-0002-0258-2484; Dumych, Tetiana/0000-0002-8489-5600; Friedrich, Ralf/0000-0001-6370-3545; Maueroder, Christian/0000-0002-7563-883X; Bilyy, Rostyslav/0000-0002-2344-1349; Munoz, Luis E/0000-0002-5395-804X; Hahn, Jonas/0000-0003-3944-2108; Biermann, Mona/0000-0003-0496-5988; Hoffmann, Markus/0000-0001-9698-9922												0027-8424					OCT 4	2016	113	40					E5856	E5865		10.1073/pnas.1602230113							WOS:000384528900012	27647892					
J	Oeckl, P; Metzger, F; Nagl, M; von Arnim, CAF; Halbgebauer, S; Steinacker, P; Ludolph, AC; Otto, M				Oeckl, Patrick; Metzger, Fabian; Nagl, Magdalena; von Arnim, Christine A. F.; Halbgebauer, Steffen; Steinacker, Petra; Ludolph, Albert C.; Otto, Markus			Alpha-, Beta-, and Gamma-synuclein Quantification in Cerebrospinal Fluid by Multiple Reaction Monitoring Reveals Increased Concentrations in Alzheimer's and Creutzfeldt-Jakob Disease but No Alteration in Synucleinopathies	MOLECULAR & CELLULAR PROTEOMICS												alpha-Synuclein (alpha Syn) is a major constituent of proteinaceous aggregates in neurodegenerative diseases such as Parkinson's disease (PD) and a potential biomarker candidate for diagnosis and treatment effects. However, studies about alpha Syn in cerebrospinal fluid (CSF) in diseases are inconsistent and mainly based on immunological assays. Quantitative information about beta-synuclein (beta Syn) and gamma-synuclein (gamma Syn) in CSF is not available. Here, we present an alternative method for the simultaneous quantification of alpha Syn, beta Syn and gamma Syn in CSF by multiple reaction monitoring (MRM) with a high sequence coverage (70%) of alpha Syn to validate previous, ELISA-based results and characterize synucleins in CSF in more detail. The MRM has high sensitivity in the low pg/ml range (3-30pg/ml full-length alpha Syn) using 200 mu l CSF. A high portion of CSF alpha Syn is present in the N-terminally acetylated form and the concentration of unmodified peptides in the nonamyloid component region is about 40% lower than in the N-terminal region. Synuclein concentrations show a high correlation with each other in CSF (r>0.80) and in contrast to alpha Syn and beta Syn, gamma Syn is not affected by blood contamination. CSF alpha Syn, beta Syn and gamma Syn concentrations were increased in Alzheimer's and Creutzfeldt-Jakob disease but not altered in PD, PD dementia (PDD), Lewy body dementia and atypical parkinsonian syndromes. The ratio beta Syn/alpha Syn was increased in PDD (1.49 +/- 0.38, p < 0.05) compared with PD (1.11 +/- 0.26) and controls (1.15 +/- 0.28). beta Syn shows a high correlation with CSF tau concentrations (r = 0.86, p < 0.0001, n = 125). In conclusion, we could not confirm previous observations of reduced alpha Syn in PD and our results indicate that CSF synuclein concentrations are rather general markers of synaptic degeneration than specific for synucleinopathies. beta syn is an attractive biomarker candidate that might be used as an alternative to or in combination with tau in AD and CJD diagnosis and in combination with alpha Syn it is a biomarker candidate for PDD.				Otto, Markus/F-4304-2015	Otto, Markus/0000-0003-4273-4267; Oeckl, Patrick/0000-0002-7652-7023												1535-9476	1535-9484				OCT	2016	15	10					3126	3138		10.1074/mcp.M116.059915							WOS:000385374800004	27507836					
J	Poujois, A; Devedjian, JC; Moreau, C; Devos, D; Chaine, P; Woimant, F; Duce, JA				Poujois, Aurelia; Devedjian, Jean-Christophe; Moreau, Caroline; Devos, David; Chaine, Pascal; Woimant, France; Duce, James A.			Bioavailable Trace Metals in Neurological Diseases	CURRENT TREATMENT OPTIONS IN NEUROLOGY												Medical treatment in Wilson's disease includes chelators (D-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators' doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apotransferrin, allows iron redistribution to avoid systemic loss of iron.				Devos, David/E-4059-2013	Devos, David/0000-0002-2417-799X												1092-8480	1534-3138				OCT	2016	18	10							46	10.1007/s11940-016-0426-1							WOS:000388289900001	27682263					
J	Koch, Y; Helferich, AM; Steinacker, P; Oeckl, P; Walther, P; Weishaupt, JH; Danzer, KM; Otto, M				Koch, Yvonne; Helferich, Anika M.; Steinacker, Petra; Oeckl, Patrick; Walther, Paul; Weishaupt, Jochen H.; Danzer, Karin M.; Otto, Markus			Aggregated alpha-Synuclein Increases S0D1 Oligomerization in a Mouse Model of Amyotrophic Lateral Sclerosis	AMERICAN JOURNAL OF PATHOLOGY												Aggregation of misfolded disease-related proteins is a hallmark of neurodegenerative diseases. Aggregate propagation accompanying disease progression has been demonstrated for different proteins (eg, for alpha-synuclein). Additional evidence supports aggregate cross-seeding activity for alpha-synuclein. For mutated superoxide dismutase 1 (S0D1), which causes familial amyotrophic lateral sclerosis (ALS), self propagation of aggregation and cell-to-cell transmission have been demonstrated in vitro. However, there is a prominent Lack of in vivo data concerning aggregation and cross-aggregation processes of SOD1. We analyzed the effect of alpha-synuclein and S0D1 seeds in cell culture using protein fragment complementation assay and intracerebral injection of cc-synuclein and S0D1 seeds into S0D1(G93A) transgenic ALS mice. Survival of injected mice was determined, and S0D1 aggregates in the facial nuclei were quantified during disease course. We found that alpha-synuclein preformed fibrils increased the oligomerization rate of S0D1 in vivo and in vitro, whereas aggregated S0D1 did not exert any effect in both experimental setups. Notably, survival of ALS mice was not changed after inoculation of preformed fibrils. We conclude that misfolded alpha-synuclein can increase S0D1 aggregation and suppose that alpha-synuclein seeds are transported from the temporal cortex to the facial nuclei. However, unlike other proteins, the further enhancement of a self-aggregation process by additional S0D1 could not be confirmed in our models.				Otto, Markus/F-4304-2015	Otto, Markus/0000-0003-4273-4267; Oeckl, Patrick/0000-0002-7652-7023												0002-9440	1525-2191				AUG	2016	186	8					2152	2161		10.1016/j.ajpath.2016.04.008							WOS:000380623500015	27322773					
J	Oeckl, P; Jardel, C; Salachas, F; Lamari, F; Andersen, PM; Bowser, R; de Carvalho, M; Costa, J; van Damme, P; Gray, E; Grosskreutz, J; Hernandez-Barral, M; Herukka, SK; Huss, A; Jeromin, A; Kirby, J; Kuzma-Kozakiewicz, M; Amador, MD; Mora, JS; Morelli, C; Muckova, P; Petri, S; Poesen, K; Rhode, H; Rikardsson, AK; Robberecht, W; Mahillo, AIR; Shaw, P; Silani, V; Steinacker, P; Turner, MR; Tuzun, E; Yetimler, B; Ludolph, AC; Otto, M				Oeckl, Patrick; Jardel, Claude; Salachas, Francois; Lamari, Foudil; Andersen, Peter M.; Bowser, Robert; de Carvalho, Mamede; Costa, Julia; van Damme, Philip; Gray, Elizabeth; Grosskreutz, Julian; Hernandez-Barral, Maria; Herukka, Sanna-Kaisa; Huss, Andre; Jeromin, Andreas; Kirby, Janine; Kuzma-Kozakiewicz, Magdalena; Amador, Maria del Mar; Mora, Jesus S.; Morelli, Claudia; Muckova, Petra; Petri, Susanne; Poesen, Koen; Rhode, Heidrun; Rikardsson, Anna-Karin; Robberecht, Wim; Rodriguez Mahillo, Ana I.; Shaw, Pamela; Silani, Vincenzo; Steinacker, Petra; Turner, Martin R.; Tuzun, Erdem; Yetimler, Berrak; Ludolph, Albert C.; Otto, Markus			Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS	AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION												OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a reverse round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n=150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p<0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 +/- 19.1%. We calculated a diagnostic cut-off of >568.5pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up.				Costa, Julia/B-7131-2008; de Carvalho, Mamede/I-6295-2019; Van Damme, Philip/A-6464-2009; Grosskreutz, Julian/G-2293-2010; Otto, Markus/F-4304-2015; Silani, Vincenzo/P-4421-2017	Costa, Julia/0000-0001-7782-6319; de Carvalho, Mamede/0000-0001-7556-0158; Van Damme, Philip/0000-0002-4010-2357; Grosskreutz, Julian/0000-0001-9525-1424; Otto, Markus/0000-0003-4273-4267; Silani, Vincenzo/0000-0002-7698-3854; Shaw, Pamela/0000-0002-8925-2567; Oeckl, Patrick/0000-0002-7652-7023; Turner, Martin/0000-0003-0267-3180												2167-8421	2167-9223				JUL-AUG	2016	17	5-6					404	413		10.3109/21678421.2016.1167913							WOS:000381024500014	27415180					
J	Turcheniuk, V; Turcheniuk, K; Bouckaert, J; Barras, A; Dumych, T; Bilyy, R; Zaitsev, V; Siriwardena, A; Wang, Q; Boukherroub, R; Szunerits, S				Turcheniuk, Volodymyr; Turcheniuk, Kostiantyn; Bouckaert, Julie; Barras, Alexandre; Dumych, Tetiana; Bilyy, Rostyslav; Zaitsev, Vladimir; Siriwardena, Aloysius; Wang, Qi; Boukherroub, Rabah; Szunerits, Sabine			Affinity of Glycan-Modified Nanodiamonds towards Lectins and Uropathogenic Escherichia Coli	CHEMNANOMAT												Nanodiamond particles (NDs) modified with glycan ligands are revealing themselves to have great promise as new nanomaterials for combating biofilm formation and as promising anti-adhesive scaffolds. Currently, the strategies at hand to formulate glycan-modified NDs (glyco-NDs) are limited to a few reports. We demonstrate herein that the photoinduced covalent attachment of unmodified sugars results in glyco-NDs with high binding affinity to lectins and a uropathogenic Escherichia coli strain (E. coli UTI89). While the binding affinities of glyco-NDs to different lectins is partially sacrificed when monosaccharides such as mannose are photochemically integrated onto NDs, in the case of disaccharides and oligosaccharides the binding affinity of glyco-NDs to lectins is preserved. Moreover, mannan-modified NDs show strong interactions with uropathogenic E. coli., suggesting the effectiveness of photochemically formed glycoNDs for disruption of E. coli-mediated biofilms.				Dumych, Tetiana/H-9450-2018; Zaitsev, Volodymyr/H-7295-2012; Bilyy, Rostyslav/A-9777-2010	Dumych, Tetiana/0000-0002-8489-5600; Zaitsev, Volodymyr/0000-0001-5067-3658; Bilyy, Rostyslav/0000-0002-2344-1349; Szunerits, Sabine/0000-0002-1567-4943													2199-692X				APR	2016	2	4					307	314		10.1002/cnma.201500229							WOS:000383772000009						
J	Turcheniuk, K; Dumych, T; Bilyy, R; Turcheniuk, V; Bouckaert, J; Vovk, V; Chopyak, V; Zaitsev, V; Mariot, P; Prevarskaya, N; Boukherroub, R; Szunerits, S				Turcheniuk, Kostiantyn; Dumych, Tetiana; Bilyy, Rostyslav; Turcheniuk, Volodymyr; Bouckaert, Julie; Vovk, Volodymyr; Chopyak, Valentyna; Zaitsev, Vladimir; Mariot, Pascal; Prevarskaya, Natasha; Boukherroub, Rabah; Szunerits, Sabine			Plasmonic photothermal cancer therapy with gold nanorods/reduced graphene oxide core/shell nanocomposites	RSC ADVANCES												Gold nanorods (Au NRs) are known for their efficient conversion of photon energy into heat, resulting in hyperthermia and suppression of tumor growth in vitro and in vivo. Au NRs are thus of great promise for photothermal therapy (PTT) of different cancers. From the point of cancer therapy, low laser powers are essential (<= 1 W cm(-2)) to ensure minimal side effects such as skin burning. Herein, we investigate the potential of polyethylene glycol functionalized reduced graphene oxide (rGO-PEG) enrobed Au NRs for the photothermal destruction of human glioblastoma astrocytoma (U87MG) cells in mice. We show that Au NRs@rGO-PEG are ideal multifunctional theranostic nanostructures that can exert efficient photothermal destruction of tumors in mice upon low doses of NIR light excitation and can act as fluorescent cellular markers due to the presence of a NIR dye integrated onto the rGO shell. Due to the specific interaction between Tat protein modified Au NRs@rGO-PEG nanostructures with the human glioblastoma astrocytoma (U87MG) cells, selective targeting of the tumor is achieved. In vivo experiments in mice show that upon irradiation of the tumor implanted in mice at 800 nm under low doses (0.7 W cm(-2)), U87MG tumor growth gets suppressed. The study demonstrates that the novel nanomaterials allow for an efficient destruction of solid tumors and might thus serve as an excellent multi-functional theranostic agent in photothermal therapeutic applications.				Chopyak, Valentyna/I-7863-2018; Bilyy, Rostyslav/A-9777-2010; Dumych, Tetiana/H-9450-2018; Zaitsev, Volodymyr/H-7295-2012; Boukherroub, Rabah/I-4826-2017	Chopyak, Valentyna/0000-0003-3127-2028; Bilyy, Rostyslav/0000-0002-2344-1349; Dumych, Tetiana/0000-0002-8489-5600; Zaitsev, Volodymyr/0000-0001-5067-3658; Boukherroub, Rabah/0000-0002-9795-9888; Mariot, Pascal/0000-0001-7226-9162; Vovk, Volodymyr/0000-0002-8411-267X; Szunerits, Sabine/0000-0002-1567-4943													2046-2069					2016	6	2					1600	1610		10.1039/c5ra24662h							WOS:000367953200090