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1. Poverty and its Representations: An Anthropological Analysis of Indigenous Knowledge and Western Science Discourses within the Sustainable Development Debate

Author: Forzo Titang, Franklin; Research Graduate Cultural Anthropology & Development Studies Faculty of Social Sciences, Katholieke Universiteit Leuven (KU Leuven) and Forzo Titang, Franklin; Research Graduate Cultural Anthropology & Development Studies Faculty of Social Sciences, Katholieke Universiteit Leuven (KU Leuven)
Abstract: Poverty continuously lays a breeding ground for capitalist orientations and perceptions of the concept in itself and “justifies” the adoption of foreign-based solutions with little or no affiliation to local and socio-cultural contexts. Meanwhile, the contextualizations surrounding the poverty debate in development aid and intervention seemingly underpin the assertion that development aid is problematic in itself given binary tensions surrounding indigenous knowledge and western science as post-modern development discourse. This paper succinctly explores the orientations of poverty within the development aid conundrum and discusses dichotomies between indigenous knowledge and western science in defining development processes in developing countries and Sub Saharan Africa. It seeks to underscore the socio economic, cultural and politically constructed “representations” of poverty by discussing theoretical standpoints to question development aid agencies’ interventions in the Global South, and the impending changes in local and community relationships as a result. The paper concludes that while anthropologists’ role within this development and knowledge debate is pivotal, it is imperative for development aid to go beyond mere economic and measurement led framings of poverty, to affix a more salient perspective of culture and local knowledge systems that will shape the understanding of poverty and guide concurrent interventions.
Published: 2019

2. Limits of multi-relational graphs

Author: Juan Alvarado, Yuyi Wang, Jan Ramon, Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Machine Learning in Information Networks [MAGNET], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Computer Science [ETH Zürich] (D-INFK), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Machine Learning in Information Networks (MAGNET), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: ACM: I.: Computing Methodologies/I.2: ARTIFICIAL INTELLIGENCE, ACM: G.: Mathematics of Computing/G.2: DISCRETE MATHEMATICS/G.2.2: Graph Theory, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Large multigraph, Graphon Theory, Markov Logic Network, Large Deviation Principle, Artificial Intelligence, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an], Software, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: International audience; Graphons are limits of large graphs. Motivated by a theoretical problem from statistical relational learning, we develop a generalization of basic results from graphon theory into the "multi-relational" setting. We show that their multi-relational counterparts, which we call multi-relational graphons, are analogically limits of large multi-relational graphs. We extend the cutdistance topology for graphons to multi-relational graphons and prove its compactness and the density of multi-relational graphs in this topology. In turn, compactness enables to prove the large deviation principle for Multi-Relational Graphs (LDP) which enables to prove the most typical random graphs constrained by marginal statistics converge asymptotically to constrained multirelational graphons with maximum entropy. We show the equivalence between a restricted version of Markov Logic Network and Multi-Relational Graphons with maximum entropy.
Published: 2022

3. Sex differences in imaging and clinical characteristics of patients from the WAKE--UP trial

Author: Anke Wouters, Lauranne Scheldeman, Hannelore Liessens, Patrick Dupont, Florent Boutitie, Bastian Cheng, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Christian Gerloff, Keith W. Muir, Norbert Nighoghossian, Salvador Pedraza, Claus Z. Simonsen, Vincent Thijs, Götz Thomalla, Robin Lemmens, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Amsterdam UMC - Amsterdam University Medical Center, Leuven Brain Institute [Leuven, Belgium] (LBI), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Aarhus University Hospital, University of Melbourne, Austin Hospital [Melbourne], Austin Health, CarMeN, laboratoire, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Sex Characteristics, Time Factors, Ischemic stroke, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, methods [Thrombolytic Therapy], wake-up, drug therapy [Stroke], therapeutic use [Tissue Plasminogen Activator], Neurology, Wake-up, methods [Diffusion Magnetic Resonance Imaging], diagnostic imaging [Stroke], ischemic stroke, Humans, drug therapy [Brain Ischemia], sex, Female, Sex, ddc:610, Neurology (clinical), Mri, MRI
Abstract: BACKGROUND AND PURPOSE: Sex-based differences in acute ischemic stroke are a well-known phenomenon. We aimed to explore these differences between women and men in the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial. METHODS: We compared baseline demographic and imaging characteristics (visual fluid-attenuated inversion recovery [FLAIR] positivity, relative FLAIR signal intensity, collateral status) between women and men in all screened patients. In randomized patients (i.e., those with diffusion-weighted imaging (DWI)-FLAIR mismatch), we evaluated a modifying role of sex on the treatment effect of alteplase in multivariable logistic regression, with treatment adjusted for National Institute of Health Stroke Scale (NIHSS) score and age. Dependent variables were modified Rankin Scale (mRS) score of 0-1 at 90 days and distribution of mRS scores at 90 days. RESULTS: Of 1362 screened patients, 529 (38.8%) were women. Women were older than men, had higher baseline NIHSS scores and smoked less frequently. FLAIR positivity of the DWI lesion was equally present in women (174/529, 33.1%) and men (273/833, 33.3%; p = 1.00) and other imaging variables also did not differ between the sexes. In a total of 503 randomized patients, of whom 178 were women (35.4%), sex did not modify the treatment effect of alteplase on mRS score 0-1 or on the total distribution of mRS scores. CONCLUSION: As in many other stroke trials, more men than women were included in the WAKE-UP trial, but the presence of a visual DWI-FLAIR mismatch and the relative FLAIR signal intensity did not differ between the sexes. The treatment effect of alteplase was not modified by sex. ispartof: EUROPEAN JOURNAL OF NEUROLOGY vol:30 issue:3 pages:641-647 ispartof: location:England status: published
Published: 2023

4. Cancer-related cognitive impairment in non-CNS cancer patients: Targeted review and future action plans in Europe

Author: European Cancer and Cognition Consortium (ECCC), Sleurs, Charlotte, Amidi, Ali, Wu, Lisa M, Kiesl, David, Zimmer, Philipp, Lange, Marie, Rogiers, Anne, Giffard, Benedicte, Binarelli, Giulia, Borghgraef, Cindy, Deprez, Sabine, Duivon, Mylène, De Ruiter, Michiel, Schagen, Sanne, Ahmed-Lecheheb, Djihane, Castel, Hélène, Buskbjerg, Cecilie R, Dos Santos, Mélanie, Joly, Florence, Perrier, Joy, Brussels Heritage Lab, Laboratory for Medical and Molecular Oncology, Clinical sciences, Medical Oncology, Tilburg University [Tilburg], Netspar, FUTURE HEALTH DEPARTMENT [KU Leuven] (KU-IBBT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Aarhus University [Aarhus], Northwestern University Feinberg School of Medicine, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Kepler University Hospital, Technische Universität Dortmund [Dortmund] (TU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Nationale Contre le Cancer (LNCC), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, University of Amsterdam [Amsterdam] (UvA), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Cancer and Cognition Consortium (ECCC) - Department of Cognitive Neuropsychology, Tilburg University, Tilburg, the Netherlands, Eustache, Francis, and Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE)
Subjects: Cognitive Dysfunction/diagnosis, Neuroimaging, clinical, rehabilitation, immune checkpoint inhibitors, Clinical, Neoplasms, preclinical, Humans, Neoplasms/therapy, Cognitive Dysfunction, risk factors, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], European consortium, neuroimaging, Rehabilitation, Hematology, Symptomatic immune-related adverse events, Preclinical, Europe, Delphi consensus, Risk factors, PRO-CTCAE™, PATIENT-REPORTED OUTCOMES, oncology, Quality of Life, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cancer-related cognitive impairment (CRCI), Biomarkers
Abstract: International audience; Cancer-related cognitive impairment (CRCI) has increasingly been identified over the last two decades in non-CNS system cancer patients. Across Europe, researchers have contributed to this effort by developing preclinical models, exploring underlying mechanisms and assessing cognitive and quality of life changes. The ultimate goal is to develop interventions to treat patients experiencing CRCI. To do so, new challenges need to be addressed requiring the implementation of multidisciplinary research groups. In this consensus paper, we summarize the state of the art in the field of CRCI combined with the future challenges and action plans in Europe. These challenges include data sharing/pooling, standardization of assessments as well as assessing additional biomarkers and neuroimaging investigations, notably through translational studies. We conclude this position paper with specific actions for Europe based on shared scientific expert opinion and stakeholders involved in the Innovative Partnership for Action Against Cancer, with a particular focus on cognitive intervention programs.
Published: 2022

5. The <scp>AhR‐SRC</scp> axis as a therapeutic vulnerability in <scp>BRAFi</scp> ‐resistant melanoma

Author: Anaïs Paris, Nina Tardif, Francesca M Baietti, Cyrille Berra, Héloïse M Leclair, Eleonora Leucci, Marie‐Dominique Galibert, Sébastien Corre, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), CHU Pontchaillou [Rennes], College of Natural Resources and Sciences, Humboldt State University, Institut National de la Santé et de la Recherche Médicale, ENV201308, CNIB, Ligue Contre le Cancer, 2016‐054, Stichting Tegen Kanker, and Université de Rennes 1
Subjects: Phenotype, cell plasticity, Receptors, Aryl Hydrocarbon, [SDV]Life Sciences [q-bio], expression, Dasatinib, melanoma, Humans, Molecular Medicine, BRAFi resistance, Protein Kinase Inhibitors
Abstract: The nongenetic mechanisms required to control tumor phenotypic plasticity and shape drug-resistance remain unclear. We show here that the Aryl hydrocarbon Receptor (AhR) transcription factor directly regulates the gene expression program associated with the acquisition of resistance to BRAF inhibitor (BRAFi) in melanoma. In addition, we show in melanoma cells that canonical activation of AhR mediates the activation of the SRC pathway and promotes the acquisition of an invasive and aggressive resistant phenotype to front-line BRAFi treatment in melanoma. This nongenetic reprogramming identifies a clinically compatible approach to reverse BRAFi resistance in melanoma. Using a preclinical BRAFi-resistant PDX melanoma model, we demonstrate that SRC inhibition with dasatinib significantly re-sensitizes melanoma cells to BRAFi. Together we identify the AhR/SRC axis as a new therapeutic vulnerability to trigger resistance and warrant the introduction of SRC inhibitors during the course of the treatment in combination with front-line therapeutics to delay BRAFi resistance. ispartof: EMBO MOLECULAR MEDICINE vol:14 issue:12 ispartof: location:England status: published
Published: 2022

6. Wavelet analysis for the solution to the wave equation with fractional noise in time and white noise in space

Author: Ciprian A. Tudor, Obayda Assaad, Laboratory of Glia Biology [Leuven, Belgium], Leuven Center for Cancer Biology (VIB-KU-CCB), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)
Subjects: Statistics and Probability, Hurst exponent, Fractional Brownian motion, Stein–Malliavin calculus, Hurst parameter estimation, 010102 general mathematics, Mathematical analysis, fractional Brownian motion, central limit theorem, White noise, Malliavin calculus, Wave equation, wavelets, 01 natural sciences, Noise (electronics), 010104 statistics & probability, symbols.namesake, Wavelet, Gaussian noise, symbols, stochastic wave equation, [MATH]Mathematics [math], 0101 mathematics, Mathematics
Abstract: International audience; Via Malliavin calculus, we analyze the limit behavior in distribution of the spatial wavelet variation for the solution to the stochastic linear wave equation with fractional Gaussian noise in time and white noise in space. We propose a wavelet-type estimator for the Hurst parameter of the this solution and we study its asymptotic properties.
Published: 2021

7. New remote cerebral microbleeds in acute ischemic stroke: an analysis of the randomized, placebo-controlled WAKE-UP trial

Author: Braemswig, Tim, Vynckier, Jan, Puig, Josep, Thijs, Vincent, Fiebach, Jochen B, Muir, Keith W, Nighoghossian, Norbert, Ebinger, Martin, Pedraza, Salvador, Thomalla, Götz, Gerloff, Christian, Endres, Matthias, Jensen, Märit, Lemmens, Robin, Schlemm, Ludwig, Nolte, Christian, Investigators, WAKE-UP, Boutitie, Florent, Galinovic, Ivana, Simonsen, Claus Z, Cheng, Bastian, Cho, Tae-Hee, Scheitz, Jan F., Fiehler, Jens, CarMeN, laboratoire, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Freie Universität Berlin, OLV Ziekenhuis Aalst Asse Ninove [Aalst, Belgium.], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Aarhus University Hospital, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), German Center for Cardiovascular Research (DZHK), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), University of Melbourne, Austin Hospital [Melbourne], Austin Health, University of Glasgow, Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)
Subjects: Science & Technology, Stroke/complications/diagnostic imaging, Clinical Neurology, complications [Brain Ischemia], diagnostic imaging [Cerebral Hemorrhage], Brain Ischemia/complications/diagnostic imaging, Magnetic Resonance Imaging, Brain Ischemia, Cerebral Hemorrhage/complications/diagnostic imaging, Stroke, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Neurology, Ischemic Stroke, diagnostic imaging [Brain Ischemia], complications [Cerebral Hemorrhage], diagnostic imaging [Stroke], Humans, complications [Stroke], Neurosciences & Neurology, ddc:610, Neurology (clinical), Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Cerebral Hemorrhage
Abstract: ispartof: JOURNAL OF NEUROLOGY vol:269 issue:10 pages:5660-5667 ispartof: location:Germany status: published
Published: 2022

8. Molecular Heterogeneity Between Paired Primary and Metastatic Lesions from Clear Cell Renal Cell Carcinoma

Author: Eduard Roussel, Lisa Kinget, Annelies Verbiest, Jessica Zucman-Rossi, Bram Boeckx, Steven Joniau, Diether Lambrechts, Maarten Albersen, Benoit Beuselinck, Zucman-Rossi, Jessica, University Hospitals Leuven [Leuven], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB)
Subjects: Molecular subtypes, Urology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Heterogeneity, Metastases, Clear cell, Renal cell carcinoma, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: UNLABELLED: Highly effective systemic treatments have globally improved outcomes in metastatic clear-cell renal cell carcinoma (m-ccRCC). However, despite many efforts, reliable biomarkers predicting individual responses are currently lacking. Moreover, mixed responses are commonly observed. We hypothesized that molecular heterogeneity between primary tumors and their metastases could flaw biomarker research based on features of the primary tumor and explain mixed responses. Therefore, we studied the heterogeneity of the ccrcc1-4 molecular subtypes across patient-matched primary and metastatic lesions over time in 62 patients with m-ccRCC who underwent both nephrectomy and metastasectomy. These subtypes characterize underlying disease biology and are associated with outcomes in both the primary and metastatic settings. We observed a concordance rate of 58% (95% confidence interval 45-71%). This concordance was not affected by the interval between nephrectomy and resection of the metastatic lesion. Across discordant pairs, the metastatic lesions mostly exhibited a less favorable molecular subtype. Moreover, primary tumors with the favorable ccrcc2 molecular subtype were characterized by favorable prognosis and a long interval between nephrectomy and metastasectomy. Conversely, tumors with the unfavorable ccrcc4 molecular subtype relapsed quickly and had poor prognosis. Thus, the considerable molecular heterogeneity between patient-matched m-ccRCC primary and metastatic lesions provides an explanation for mixed responses to systemic therapy and could impact the development of biomarker studies in which the primary tumor is often considered a surrogate for metastatic disease. PATIENT SUMMARY: We studied primary tumors and metastases from patients with kidney cancer and found considerable heterogeneity in their molecular features. This heterogeneity explains mixed responses to systemic therapy and is important to take into account in future biomarker studies for this disease. ispartof: EUROPEAN UROLOGY OPEN SCIENCE vol:40 pages:54-57 ispartof: location:Netherlands status: published
Published: 2022

9. Effects of spironolactone on serum markers of fibrosis in people at high risk of developing heart failure

Author: Joseph J Cuthbert, Pierpaolo Pellicori, Johannes Petutschnigg, Franco Cosmi, Blerim Mujaj, João Pedro Ferreira, Fozia Z Ahmed, Nicolas Girerd, Faiez Zannad, Roberto Latini, Timothy Collier, Patrick Rossignol, Beatrice Mariottoni, Jan A. Staessen, John G.F. Cleland, Stephane Heymans, Andrew L. Clark, Job A J Verdonschot, Arantxa González, Hans-Peter Brunner-La Rocca, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cortona Hospital, Department of Cardiology, Maastricht University Medical Center, Manchester Heart Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, London School of Hygiene and Tropical Medicine (LSHTM), Castle Hill Hospital, Hull York Medical School, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], DZHK (German Center of Cardiovascular Research), Partner Site Berlin, Research Unit Hypertension and Cardiovascular Epidemiology [Louvain, Belgique], Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Queensland University of Technology [Brisbane] (QUT), Maastricht University [Maastricht], Cardiovascular Research Institute [Maastricht], Maastricht University Medical Centre - MUMC [Maastricht, The Netherlands], IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21, Contrat de plan Etat-lorraine and FEDER lorraine, British Heart Foundation Centre of Research Excellence grant number RE/18/6/34217, ERA-Net-CVD project MacroERA, 01KL1706, IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), European Project: 305507,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,HOMAGE(2013), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), DE CARVALHO, Philippe, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, and Heart OMics in AGEing - HOMAGE - - EC:FP7:HEALTH2013-02-01 - 2019-01-31 - 305507 - VALID
Subjects: Male, Aging, [SDV]Life Sciences [q-bio], ALDOSTERONE ANTAGONISM, 030204 cardiovascular system & hematology, Spironolactone, Ventricular Function, Left, Coronary artery disease, chemistry.chemical_compound, DOUBLE-BLIND, 0302 clinical medicine, Interquartile range, Natriuretic Peptide, Brain, Clinical endpoint, Natriuretic peptide, Prospective Studies, COLLAGEN TURNOVER, Ejection fraction, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Atrial fibrillation, DIASTOLIC DYSFUNCTION, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV] Life Sciences [q-bio], PRESERVED EJECTION FRACTION, BRAIN NATRIURETIC PEPTIDE, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, NT-PROBNP, EXTRACELLULAR-MATRIX TURNOVER, medicine.drug_class, BIOMARKERS, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, Aged, Heart Failure, business.industry, Stroke Volume, Study design, medicine.disease, Fibrosis, Peptide Fragments, Diabetes Mellitus, Type 2, chemistry, HOMAGE, MYOCARDIAL-INFARCTION, Heart failure, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; AIMS:Asymptomatic patients with coronary artery disease (CAD), hypertension and/or type 2 diabetes mellitus (T2DM) are at greater risk of developing heart failure (HF). Fibrosis, leading to myocardial and vascular dysfunction, might be an important pathway of progression. The Heart OMics in AGing (HOMAGE) trial aims to investigate the effects of spironolactone on serum markers of collagen metabolism and on cardiovascular structure and function in people at risk of developing HF and potential interactions with a marker of fibrogenic activity, galectin-3.METHODS AND RESULTS:The HOMAGE trial is a prospective, randomised, open-label, blinded endpoint (PROBE) study comparing spironolactone (up to 50 mg/day) and standard care over 9 months in people with clinical risk factors for developing HF, including hypertension, CAD and T2DM, and elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP, 125 to 1000 ng/L) or B-type natriuretic peptide (BNP, 35 to 280 ng/L). Exclusion criteria included left ventricular ejection fraction
Published: 2020

10. Blockade of the pro‐fibrotic reaction mediated by the miR‐143/‐145 cluster enhances the responses to targeted therapy in melanoma

Author: Serena Diazzi, Alberto Baeri, Julien Fassy, Margaux Lecacheur, Oskar Marin‐Bejar, Christophe A Girard, Lauren Lefevre, Caroline Lacoux, Marie Irondelle, Carine Mounier, Marin Truchi, Marie Couralet, Mickael Ohanna, Alexandrine Carminati, Ilona Berestjuk, Frederic Larbret, David Gilot, Georges Vassaux, Jean‐Christophe Marine, Marcel Deckert, Bernard Mari, Sophie Tartare‐Deckert, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Equipe de recherche sur les relations matrice extracellulaire-cellules (ERRMECe), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), CY Cergy Paris Université (CY)-CY Cergy Paris Université (CY), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, G.0929.16N, Fonds Wetenschappelijk Onderzoek, Centre National de la Recherche Scientifique, Ligue Contre le Cancer, INCA_12673, Institut National Du Cancer, ANR‐PRCI‐18‐CE92‐0009‐01, Agence Nationale de la Recherche, Canceropôle PACA, Fondation ARC pour la Recherche sur le Cancer, and TARTARE-DECKERT, Sophie
Subjects: Indoles, MIGRATION, [SDV]Life Sciences [q-bio], MAPK inhibitors, Research & Experimental Medicine, Mechanotransduction, Cellular, MIR-145, Cell Line, Tumor, melanoma, nintedanib, Humans, DRUGS, VULNERABILITY, Science & Technology, microRNA, Microfilament Proteins, fibrosis, [SDV] Life Sciences [q-bio], MicroRNAs, DIFFERENTIATION, Medicine, Research & Experimental, BRAF INHIBITOR RESISTANCE, SURVIVAL, Molecular Medicine, Neoplasm Recurrence, Local, Carrier Proteins, Life Sciences & Biomedicine
Abstract: Lineage dedifferentiation toward a mesenchymal-like state displaying myofibroblast and fibrotic features is a common mechanism of adaptive and acquired resistance to targeted therapy in melanoma. Here, we show that the anti-fibrotic drug nintedanib is active to normalize the fibrous ECM network, enhance the efficacy of MAPK-targeted therapy, and delay tumor relapse in a preclinical model of melanoma. Acquisition of this resistant phenotype and its reversion by nintedanib pointed to miR-143/-145 pro-fibrotic cluster as a driver of this mesenchymal-like phenotype. Upregulation of the miR-143/-145 cluster under BRAFi/MAPKi therapy was observed in melanoma cells in vitro and in vivo and was associated with an invasive/undifferentiated profile. The 2 mature miRNAs generated from this cluster, miR-143-3p and miR-145-5p, collaborated to mediate transition toward a drug-resistant undifferentiated mesenchymal-like state by targeting Fascin actin-bundling protein 1 (FSCN1), modulating the dynamic crosstalk between the actin cytoskeleton and the ECM through the regulation of focal adhesion dynamics and mechanotransduction pathways. Our study brings insights into a novel miRNA-mediated regulatory network that contributes to non-genetic adaptive drug resistance and provides proof of principle that preventing MAPKi-induced pro-fibrotic stromal response is a viable therapeutic opportunity for patients on targeted therapy. ispartof: EMBO MOLECULAR MEDICINE vol:14 issue:3 ispartof: location:England status: published
Published: 2022

11. Antimetabolic cooperativity with the clinically approved kidrolase and tyrosine kinase inhibitors to eradicate cml stem cells

Author: Patrice Maboudou, Véronique Maguer-Satta, Bruno Quesnel, Quentin Fovez, Raeeka Khamari, William Laine, Jérôme Kluza, Sandrine Jeanpierre, Didier Bouscary, Béatrice Turcq, Philippe Marchetti, Salim Dekiouk, Anne Trinh, Marie Joncquel, Thierry Idziorek, Valérie Coiteux, Bart Ghesquière, Nicolas Germain, Francois-Xavier Mahon, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), This work received a financial support from INSERM, UNIVERSITE DE LILLE, Ligue contre le Cancer (to PM and JK), a special financial support from the Association pour l’Etude des Anomalies Congénitales Neurodev of Pr. B. Poupard (to PM). AT is a recipient of a CHRU Lille-Région Nord-Pas de Calais fellowship. RK and QF are recipients of a University of Lille fellowship., Dupuis, Christine, Centre National de la Recherche Scientifique (CNRS), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Institut pour la recherche sur le cancer de Lille [Lille] [IRCL], Actions for OnCogenesis understanding and Target Identification in ONcology [ACTION], Institut Cochin [IC UM3 (UMR 8104 / U1016)], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven]
Subjects: Synthetic lethality, [SDV]Life Sciences [q-bio], Cooperativity, Apoptosis, BCR-ABL1 (B Cell Receptor-Abelson), LSC (leukemic stem cell), L asparaginase, Mice, CML (chronic myeloid leukemia), TKI (tyrosine kinase inhibitors), Cell Line, Tumor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, LSC, Animals, Asparaginase, Humans, Metabolic addiction, Stem-like cells, Molecular Biology, Protein Kinase Inhibitors, Internal medicine, Metabolic stress, Cell Proliferation, Chemistry, stem-like cells, Cell Biology, Protein-Tyrosine Kinases, RC31-1245, synthetic lethality, respiratory tract diseases, [SDV] Life Sciences [q-bio], Drug Resistance, Neoplasm, metabolic addiction, Cancer research, Imatinib Mesylate, Neoplastic Stem Cells, Original Article, metabolic stress, Stem cell, Asparagine, Tyrosine kinase
Abstract: OBJECTIVE: Long-term treatment with tyrosine kinase inhibitors (TKI) represents an effective cure for chronic myeloid leukemia (CML) patients and discontinuation of TKI therapy is now proposed to patient with deep molecular responses. However, evidence demonstrating that TKI are unable to fully eradicate dormant leukemic stem cells (LSC) indicate that new therapeutic strategies are needed to control LSC and to prevent relapse. In this study we investigated the metabolic pathways responsible for CML surviving to imatinib exposure and its potential therapeutic utility to improve the efficacy of TKI against stem-like CML cells. METHODS: Using complementary cell-based techniques, metabolism was characterized in a large panel of BCR-ABL+ cell lines as well as primary CD34+ stem-like cells from CML patients exposed to TKI and L-Asparaginases. Colony forming cell (CFC) assay and flow cytometry were used to identify CML progenitor and stem like-cells. Preclinical models of leukemia dormancy were used to test the effect of treatments. RESULTS: Although TKI suppressed glycolysis, compensatory glutamine-dependent mitochondrial oxidation supported ATP synthesis and CML cell survival. Glutamine metabolism was inhibited by L-asparaginases such as Kidrolase or Erwinase without inducing predominant CML cell death. However, clinically relevant concentrations of TKI render CML cells susceptible to Kidrolase. The combination of TKI with Lasparaginase reactivates the intinsic apoptotic pathway leading to efficient CML cell death. CONCLUSION: Targeting glutamine metabolism with the FDA-approved drug, Kidrolase in combination with TKI that suppress glycolysis represents an effective and widely applicable therapeutic strategy for eradicating stem-like CML cells. ispartof: MOLECULAR METABOLISM vol:55 ispartof: location:Germany status: published
Published: 2022

12. Diffusion-Weighted Imaging and Fluid-Attenuated Inversion Recovery Quantification to Predict Diffusion-Weighted Imaging-Fluid-Attenuated Inversion Recovery Mismatch Status in Ischemic Stroke With Unknown Onset

Author: Lauranne Scheldeman, Anke Wouters, Patrick Dupont, Søren Christensen, Florent Boutitie, Bastian Cheng, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Christian Gerloff, Keith W. Muir, Norbert Nighoghossian, Salvador Pedraza, Claus Z. Simonsen, Vincent Thijs, Götz Thomalla, Robin Lemmens, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Amsterdam UMC - Amsterdam University Medical Center, Leuven Brain Institute [Leuven, Belgium] (LBI), GrayNumber Analytics [Lomma, Sweden] (GNA), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Aarhus University Hospital, University of Melbourne, Austin Hospital [Melbourne], Austin Health, CarMeN, laboratoire, and Neurology
Subjects: Advanced and Specialized Nursing, diagnostic imaging [Ischemic Stroke], sensitivity and specificity, [SDV]Life Sciences [q-bio], United States, brain ischemia, [SDV] Life Sciences [q-bio], Stroke, retrospective studies, Diffusion Magnetic Resonance Imaging, methods [Magnetic Resonance Imaging], methods [Diffusion Magnetic Resonance Imaging], Humans, magnetic resonance imaging, cardiovascular diseases, Neurology (clinical), ddc:610, Cardiology and Cardiovascular Medicine, logistic models, Ischemic Stroke
Abstract: Background: Visual rating of diffusion-weighted imaging (DWI)–fluid-attenuated inversion recovery (FLAIR) mismatch can be challenging. We evaluated quantification of DWI and FLAIR to predict DWI-FLAIR mismatch status in ischemic stroke. Methods: In screened patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke), we retrospectively studied relative DWI (rDWI SI) and FLAIR signal intensity (rFLAIR SI). We defined the optimal mean rFLAIR SI and interquartile range of the rDWI SI in the DWI lesion to predict DWI-FLAIR mismatch status. We investigated agreement between each quantitative parameter and the DWI-FLAIR mismatch and the association between both quantitative parameters. We evaluated the predictive value of the quantitative parameters for excellent functional outcome by logistic regression, adjusted for DWI lesion volume, treatment, age, and National Institutes of Health Stroke Scale score. Results: In the rFLAIR and rDWI SI analysis, 213/369 and 241/421 subjects respectively had a DWI-FLAIR mismatch. A mean rFLAIR SI cutoff of 1.09 and interquartile range rDWI SI cutoff of 0.47 were optimal to predict the DWI-FLAIR mismatch with a sensitivity and specificity of 77% (95% CI, 71%–83%) and 67% (95% CI, 59%–74%), and 76% (95% CI, 70%–81%) and 72% (95% CI, 65%–79%), respectively. For both quantitative parameters, agreement with the DWI-FLAIR mismatch was fair (73%, κ=0.44 [95% CI, 0.35–0.54] for rFLAIR and 74%, κ=0.48 [95% CI, 0.39–0.56] for rDWI). Both quantitative parameters correlated moderately (Pearson R=0.54 [95% CI, 0.46–0.61]; P P =0.01). Conclusions: Agreement between the quantitative and qualitative approach may be insufficient to advocate DWI or FLAIR quantification as alternative for visual rating.
Published: 2022

13. Timing evolution of lobular breast cancer through phylogenetic analysis

Author: Danai Fimereli, David Venet, Mattia Rediti, Bram Boeckx, Marion Maetens, Samira Majjaj, Ghizlane Rouas, Caterina Marchio, Francois Bertucci, Odette Mariani, Maria Capra, Giuseppina Bonizzi, Federica Contaldo, Christine Galant, Gert Van den Eynden, Roberto Salgado, Elia Biganzoli, Anne Vincent-Salomon, Giancarlo Pruneri, Denis Larsimont, Diether Lambrechts, Christine Desmedt, David N. Brown, Françoise Rothé, Christos Sotiriou, Université libre de Bruxelles (ULB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Università degli studi di Torino = University of Turin (UNITO), Candiolo Cancer Institute (IRCCS), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Cliniques Universitaires Saint-Luc [Bruxelles], Breast Cancer Translational Research Laboratory, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Translational Cancer Research Unit [Antwerp], Università degli Studi di Milano = University of Milan (UNIMI), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and European Institute of Oncology [Milan] (ESMO)
Subjects: Metastatic dissemination, BRANCHED EVOLUTION, [SDV]Life Sciences [q-bio], Breast Neoplasms, Research & Experimental Medicine, General Biochemistry, Genetics and Molecular Biology, Lobular, Medicine, General & Internal, Breast cancer, Tumour progression, General & Internal Medicine, REVEALS, Humans, Breast, Phylogeny, Retrospective Studies, Science & Technology, LANDSCAPE, Carcinoma, General Medicine, Distant metastasis, Heterogeneity, Female, Carcinoma, Lobular, GENOMIC CHARACTERIZATION, Medicine, Research & Experimental, METASTASIS, Life Sciences & Biomedicine
Abstract: BACKGROUND: Late distant recurrence is a challenge for the treatment of invasive lobular carcinoma (ILC) of the breast. Despite in-depth characterisation of primary ILC, the molecular landscape of metastatic ILC is still only partially understood. METHODS: We retrospectively identified 38 ILC patients from the tissue banks of six European institutions. DNA extracted from patient matched primary and metastatic FFPE tissue blocks was whole genome sequenced to compute somatic copy number aberrations. This, in turn, was used to infer the evolutionary history of these patients. FINDINGS: The data show different metastatic seeding patterns, with both an early and late divergence of the metastatic lineage observed in ILC. Additionally, cascading dissemination from a metastatic precursor was a dominant rule. Alterations in key cancer driver genes, such as TP53 or CCND1, were acquired early while additional aberrations were present only in the metastatic branch. In about 30% of the patients, the metastatic lineage harboured less aberrations than the primary tumour suggesting a period of tumour dormancy or prolonged adaptation at the distant site. This phenomenon was mostly observed in tumours from de novo metastatic patients. INTERPRETATION: Our results provide insights into ILC evolution and offer potential paths for optimised ILC care. FUNDING: This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research Foundation (BCRF) and the Belgian Fonds National de la Recherche Scientifique (F.R.S-FNRS). ispartof: EBIOMEDICINE vol:82 ispartof: location:Netherlands status: published
Published: 2022

14. Rallying Around the EU Flag: Russia's Invasion of Ukraine and Attitudes Toward European Integration

Author: Nils D. Steiner, Ruxanda Berlinschi, Etienne Farvaque, Jan Fidrmuc, Philipp Harms, Alexander Mihailov, Michael Neugart, Piotr Stanek, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University [JGU], Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Lille économie management - UMR 9221 [LEM], University of Reading [UOR], Technische Universität Darmstadt - Technical University of Darmstadt [TU Darmstadt], Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Lille économie management - UMR 9221 (LEM), Université d'Artois (UA)-Université catholique de Lille (UCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Reading (UOR), Technische Universität Darmstadt - Technical University of Darmstadt (TU Darmstadt), and Cracow University of Economics
Subjects: COUNTRIES, rally around the flag, Economics and Econometrics, History, EU attitudes, Polymers and Plastics, Economics, SATISFACTION, IMPACT, Political Science, Social Sciences, EUROSCEPTICISM, DEMOCRACY, external threat, Industrial and Manufacturing Engineering, Russia, PUBLIC SUPPORT, Government & Law, Business & Economics, Business and International Management, International Relations, EDUCATION, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, General Business, Management and Accounting, Political Science and International Relations, IDENTITY, POPULARITY, European integration, Ukraine
Abstract: This article uses a survey amongst students at European universities to explore whether Russia's invasion of Ukraine has affected attitudes towards European integration. Some respondents completed the survey just before Russia's assault on 24 February 2022, and some did so just afterwards, thus delivering a quasi-experimental design situation, which we exploit. Our results suggest that the ominous news about the Russian attack increased the participants' interest in EU politics, consolidated their attachment to the EU and made them more mindful and appreciative of the benefits of deeper European integration. In effect, the war so close to the EU Eastern border provoked a rally around the supranational EU flag, with convergence of public opinion towards shared European values.
Published: 2022

15. Early effect of thrombolysis on structural brain network organisation after anterior-circulation stroke in the randomized WAKE-UP trial

Author: Eckhard Schlemm, Märit Jensen, Amy Kuceyeski, Keith Jamison, Thies Ingwersen, Carola Mayer, Alina Königsberg, Florent Boutitie, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Jens Fiehler, Ivana Galinovic, Robin Lemmens, Keith W. Muir, Norbert Nighoghossian, Salvador Pedraza, Josep Puig, Claus Z. Simonsen, Vincent Thijs, Anke Wouters, Christian Gerloff, Götz Thomalla, Bastian Cheng, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Weill Cornell Medicine [Cornell University], Cornell University [New York], University Hospital Hamburg-Eppendorf, Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Aarhus University Hospital, University of Melbourne, Austin Hospital [Melbourne], Austin Health, Amsterdam UMC - Amsterdam University Medical Center, Weill Cornell Medicine [New York], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CarMeN, laboratoire
Subjects: [SDV.BA] Life Sciences [q-bio]/Animal biology, RECANALIZATION, Neuroimaging, CONNECTOME, Brain Ischemia, Fibrinolytic Agents, CONNECTIVITY, therapeutic use [Fibrinolytic Agents], diagnostic imaging [Stroke], ischemic stroke, systemic thrombolysis, Humans, Thrombolytic Therapy, Radiology, Nuclear Medicine and imaging, structural connectivity, ACUTE ISCHEMIC-STROKE, ddc:610, diagnostic imaging [Brain], adverse effects [Tissue Plasminogen Activator], Science & Technology, Radiological and Ultrasound Technology, network neuroscience, [SDV.BA]Life Sciences [q-bio]/Animal biology, Radiology, Nuclear Medicine & Medical Imaging, Neurosciences, Brain, ASSOCIATION, methods [Thrombolytic Therapy], RECOVERY, adverse effects [Fibrinolytic Agents], COGNITIVE IMPAIRMENT, REGIONS, adverse effects [Thrombolytic Therapy], DYSFUNCTION, drug therapy [Stroke], Stroke, therapeutic use [Tissue Plasminogen Activator], Treatment Outcome, Neurology, TISSUE, diagnostic imaging [Brain Ischemia], Tissue Plasminogen Activator, drug therapy [Brain Ischemia], Neurosciences & Neurology, Neurology (clinical), Anatomy, Life Sciences & Biomedicine
Abstract: The symptoms of acute ischemic stroke can be attributed to disruption of the brain network architecture. Systemic thrombolysis is an effective treatment that preserves structural connectivity in the first days after the event. Its effect on the evolution of global network organisation is, however, not well understood. We present a secondary analysis of 269 patients from the randomized WAKE-UP trial, comparing 127 imaging-selected patients treated with alteplase with 142 controls who received placebo. We used indirect network mapping to quantify the impact of ischemic lesions on structural brain network organisation in terms of both global parameters of segregation and integration, and local disruption of individual connections. Network damage was estimated before randomization and again 22 to 36 h after administration of either alteplase or placebo. Evolution of structural network organisation was characterised by a loss in integration and gain in segregation, and this trajectory was attenuated by the administration of alteplase. Preserved brain network organization was associated with excellent functional outcome. Furthermore, the protective effect of alteplase was spatio-topologically nonuniform, concentrating on a subnetwork of high centrality supported in the salvageable white matter surrounding the ischemic cores. This interplay between the location of the lesion, the pathophysiology of the ischemic penumbra, and the spatial embedding of the brain network explains the observed potential of thrombolysis to attenuate topological network damage early after stroke. Our findings might, in the future, lead to new brain network-informed imaging biomarkers and improved prognostication in ischemic stroke. ispartof: HUMAN BRAIN MAPPING vol:43 issue:16 pages:5053-5065 ispartof: location:United States status: published
Published: 2022

16. Patient-Reported Quality of Life After Intravenous Alteplase for Stroke in the WAKE-UP Trial

Author: Märit Jensen, Susanne Sehner, Bastian Cheng, Eckhard Schlemm, Fanny Quandt, Ewgenia Barow, Karl Wegscheider, Florent Boutitie, Martin Ebinger, Matthias Endres, Jochen B. Fiebach, Vincent Thijs, Robin Lemmens, Keith W. Muir, Norbert Nighoghossian, Salvador Pedraza, Claus Z. Simonsen, Götz Thomalla, Christian Gerloff, CarMeN, laboratoire, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Hospital Hamburg-Eppendorf, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Biostatistiques [Lyon], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical Park Berlin Humboldtmühle [Berlin, Germany] (MPBH), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Melbourne, Austin Hospital [Melbourne], Austin Health, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta - Girona Biomedical Research Institute (IDIBGI), Aarhus University Hospital, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: drug therapy [Ischemic Stroke], [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Treatment Outcome, Tissue Plasminogen Activator, chemically induced [Stroke], Quality of Life, Humans, ddc:610, Patient Reported Outcome Measures, Neurology (clinical), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, drug therapy [Stroke]
Abstract: Background and ObjectivesIntravenous alteplase improves functional outcome after acute ischemic stroke. However, little is known about the effects on self-reported health-related quality of life (HRQoL).MethodsWAKE-UP was a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in stroke with unknown onset time. HRQoL was assessed using the EuroQol five-dimensional questionnaire (EQ-5D) at 90 days, comprising the EQ-5D index and the EQ visual analogue scale (VAS). Functional outcome was assessed by the modified Rankin Scale (mRS). We calculated the effect of treatment on EQ-5D index and EQ VAS using multiple linear regression models. Mediation analysis was performed on stroke survivors to explore the extent to which the effect of alteplase on HRQoL was mediated by functional outcome.ResultsAmong 490 stroke survivors, the EQ-5D index was available for 452 (92.2%), of whom 226 (50%) were assigned to treatment with alteplase and 226 (50%) to placebo. At 90 days, mean EQ-5D index was higher, reflecting a better health state, in patients randomized to treatment with alteplase than with placebo (0.75 vs 0.67) with an adjusted mean difference of 0.07 (95% CI 0.02–0.12,p= 0.005). In addition, mean EQ VAS was higher with alteplase than with placebo (72.6 vs 64.9), with an adjusted mean difference of 7.6 (95% CI 3.9–11.8,p< 0.001). Eighty-five percent of the total treatment effect of alteplase on the EQ-5D index was mediated using the mRS score while there was no significant direct effect. By contrast, the treatment effect on the EQ VAS was mainly through the direct pathway (60%), whereas 40% was mediated by the mRS.DiscussionAssessment of patient-reported outcome measures reveals a potential benefit of intravenous alteplase for HRQoL beyond improvement of functional outcome.Trial Registration InformationClinicalTrials.govnumber,NCT01525290; EudraCT number, 2011-005906-32.
Published: 2022

17. Blockade of pro-fibrotic response mediated by the miR-143/-145 cluster prevents targeted therapy-induced phenotypic plasticity and resistance in melanoma

Author: Couralet M, Caroline Lacoux, C.M. Mounier, Frédéric Larbret, Irondelle M, Christophe Girard, Berestjuk I, Diazzi S, Bernard Mari, Carminati A, Alberto Baeri, Marcel Deckert, Jean-Christophe Marine, Lise Lefèvre, Oskar Marín-Béjar, Marin Truchi, Margaux Lecacheur, Sophie Tartare-Deckert, Julien Fassy, Georges Vassaux, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Girard, christophe, Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, biology, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Actin cytoskeleton, Targeted therapy, Extracellular matrix, Focal adhesion, 03 medical and health sciences, Crosstalk (biology), 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Downregulation and upregulation, 030220 oncology & carcinogenesis, biology.protein, Cancer research, medicine, Myofibroblast, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, 030304 developmental biology, Fascin
Abstract: Lineage dedifferentiation towards a mesenchymal-like state is a common mechanism of adaptive response and resistance to targeted therapy in melanoma. Yet, the transcriptional network driving this phenotypic plasticity remains elusive. Remarkably, this cellular state displays myofibroblast and fibrotic features and escapes MAPK inhibitors (MAPKi) through extracellular matrix (ECM) remodeling activities. Here we show that the anti-fibrotic drug Nintedanib/BIBF1120 is active to normalize the fibrous ECM network, enhance the efficacy of MAPK-targeted therapy and delay tumor relapse in a pre-clinical model of melanoma. We also uncovered the molecular networks that regulate the acquisition of this resistant phenotype and its reversion by Nintedanib, pointing the miR-143/-145 pro-fibrotic cluster as a driver of the therapy-resistant mesenchymal-like phenotype. Upregulation of the miR-143/-145 cluster under BRAFi/MAPKi therapy was observed in melanoma cells in vitro and in vivo and was associated with an invasive/undifferentiated profile of resistant cells. The 2 mature miRNAs generated from this cluster, miR-143-3p and miR-145-5p collaborated to mediate phenotypic transition towards a drug resistant undifferentiated mesenchymal-like state by targeting Fascin actin-bundling protein 1 (FSCN1), modulating the dynamic crosstalk between the actin cytoskeleton and the ECM through the regulation of focal adhesion dynamics as well as contributing to a fine-tuning of mechanotransduction pathways. Our study brings insights into a novel miRNA-mediated regulatory network that contributes to non-genetic adaptive drug resistance and provides proof-of-principle that preventing MAPKi-induced pro-fibrotic stromal response is a viable therapeutic opportunity for patients on targeted therapy.
Published: 2021

18. Strength of forest edge effects on litter‐dwelling macro‐arthropods across Europe is influenced by forest age and edge properties

Author: Emilie Gallet-Moron, Willem Proesmans, Monika Wulf, Lander Baeten, Brice Giffard, Marc Deconchat, Jaan Liira, Sam Van de Poel, Dries Bonte, Pallieter De Smedt, Martin Diekmann, Vincent Le Roux, Martin Hermy, Kris Verheyen, Emilie Andrieu, Sara A. O. Cousins, Jörg Brunet, Johan Van Keer, Alicia Valdés, Ludmilla Martin, Rieneke Vanhulle, Guillaume Decocq, Forest & Nature Lab, Universiteit Gent = Ghent University [Belgium] (UGENT), Independent, Dynamiques Forestières dans l'Espace Rural (DYNAFOR), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro), Université de Picardie Jules Verne (UPJV), Southern Swedish Forest Research Centre, Swedish University of Agricultural Sciences (SLU), Stockholm University, University of Bremen, Institute of Ecology and Earth Sciences [Tartu], University of Tartu, Department of Ecology, Environment and Plant Sciences, Leibniz-Zentrum für Agrarlandschaftsforschung = Leibniz Centre for Agricultural Landscape Research (ZALF), Division of Forest, Nature and Landscape, Department of Earth and Environmental Sciences [Leuven] (EES), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), and Rejmanek, Marcel
Subjects: 0106 biological sciences, GRASSLAND, DISTRIBUTION PATTERNS, Evolution, [SDV]Life Sciences [q-bio], Soil biology, Biodiversity & Conservation, BEETLE ASSEMBLAGES, Beta diversity, edge effects, Environmental Sciences & Ecology, ECOSYSTEM SERVICES, Generalist and specialist species, 010603 evolutionary biology, 01 natural sciences, [SHS]Humanities and Social Sciences, Ecosystem services, agricultural landscapes, Behavior and Systematics, Abundance (ecology), SPILLOVER, Ecology, Evolution, Behavior and Systematics, Abiotic component, forest fragmentation, Science & Technology, Ecology, Land use, 010604 marine biology & hydrobiology, Biology and Life Sciences, nutrient cycling, 15. Life on land, Geography, HABITAT FRAGMENTATION, Earth and Environmental Sciences, Litter, Biodiversity Conservation, beta diversity, VEGETATION, MILLIPEDES, COMMUNITIES, Life Sciences & Biomedicine, soil fauna, RESPONSES, natural pest control
Abstract: © 2019 The Authors. Diversity and Distributions Published by John Wiley & Sons Ltd Aim: Forests are highly fragmented across Western Europe, making forest edges important features in many agricultural landscapes. Forest edges are subject to strong abiotic gradients altering the forest environment and resulting in strong biotic gradients. This has the potential to change the forest's capacity to provide multiple ecosystem services such as nutrient cycling, carbon sequestration and natural pest control. Soil organisms play a key role in this perspective; however, these taxa are rarely considered in forest edge research. Location: A latitudinal gradient of 2,000 km across Western Europe. Methods: We sampled six dominant taxa of litter-dwelling macro-arthropods (carabid beetles, spiders, harvestmen, centipedes, millipedes and woodlice) in forest edges and interiors of 192 forest fragments in 12 agricultural landscapes. We related their abundance and community composition to distance from the edge and the interaction with forest age, edge orientation and edge contrast (contrast between land use types at either side of the edge). Results: Three out of six macro-arthropod taxa have higher activity-density in forest edges compared to forest interiors. The abundance patterns along forest edge-to-interior gradients interacted with forest age. Forest age and edge orientation also influenced within-fragment compositional variation along the forest edge-to-interior gradient. Edge contrast influenced abundance gradients of generalist predators. In general, older forest fragments, south-oriented edges and edges along structurally more continuous land use (lower contrast between forest and adjacent land use) resulted in stronger edge-to-interior gradients while recent forests, north-oriented edges and sharp land use edges induced similarity between forest edge and interior along the forest edge-to-interior gradients in terms of species activity-density and composition. Main conclusions: Edge effects on litter-dwelling macro-arthropods are anticipated to feedback on important ecosystem services such as nutrient cycling, carbon sequestration and natural pest control from small forest fragments. ispartof: DIVERSITY AND DISTRIBUTIONS vol:25 issue:6 pages:963-974 status: published
Published: 2019

19. Comparative meta-analysis of cystic fibrosis cell models suggests partial endothelial-to-mesenchymal transition

Author: Mathias Declercq, Peter Witters, Peter Carmeliet, Siham Bousfia, Lucas Treps, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratory of Angiogenesis and Vascular Metabolism [Leuven, Belgium] (VIB-CCB), Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Cancer Institute [Leuven, Belgium] (LKI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, Epithelial-Mesenchymal Transition, Cystic Fibrosis, Cell, Cystic Fibrosis Transmembrane Conductance Regulator, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, Cystic fibrosis, Endothelial activation, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Inducer, Ion transporter, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Ion Transport, Transition (genetics), business.industry, Mesenchymal stem cell, medicine.disease, medicine.anatomical_structure, Pediatrics, Perinatology and Child Health, Cancer research, Disease Progression, business
Abstract: International audience; The mesenchymal conversion of epithelial cells (EMT) has been suggested as a potential contributor in cystic fibrosis (CF) disease progression. Endothelial cells (EndCs), the cells lining blood vessels, express functional CFTR and CFTR impairment promotes endothelial activation and dysfunction. However, if the mesenchymal switch also exists in CF EndCs remains uncharacterized. To understand whether the endothelial-to-mesenchymal transition (EndMT) could occur in CF, we have conducted a transcriptomic meta-analysis of primary CFTR-impaired and patient-derived EndCs, and further compared our results to data from CF epithelial cells (EpCs) where EMT has been demonstrated. As compared to EpCs, we show that CFTR-impaired EndCs display a limited signature of EndMT, and that expression of the mesenchymal inducer Twist1 remained unchanged. Nonetheless, the use of CFTR modulators reduced the expression of mesenchymal markers from CF patient-derived EndCs, suggesting an additional therapeutic added-value next to the known effect on CFTR ion transport.
Published: 2021

20. MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma

Author: Annouschka Laenen, Lisa Kinget, Gabrielle Couchy, Annelies Verbiest, Bram Boeckx, Maarten Albersen, Lucía Inglada-Pérez, Osvaldo Graña-Castro, Marcella Baldewijns, Stefano Caruso, Loïc Vanginderhuysen, Jessica Zucman-Rossi, Eduard Roussel, Cristina Rodríguez-Antona, Diether Lambrechts, Benoit Beuselinck, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Spanish National Cancer Research Center (CNIO), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Cancer Research, renal cell carcinoma, [SDV]Life Sciences [q-bio], miR-30b-3p, miR-20a-5p, miR-335-3p, lcsh:RC254-282, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, SATB2, Renal cell carcinoma, microRNA, medicine, Adverse effect, bone metastasis, Science & Technology, miR-139-3p, business.industry, RNA, Bone metastasis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Clear cell renal cell carcinoma, 030104 developmental biology, miR-23a-3p, Oncology, 030220 oncology & carcinogenesis, Potential biomarkers, Cancer research, business, Life Sciences & Biomedicine, miR-27a-3p
Abstract: Simple Summary Bone metastases cause substantial morbidity and implicate worse clinical outcomes for clear-cell renal cell carcinoma patients. MicroRNAs are small RNA molecules that modulate gene translation and are involved in the development of cancer and metastasis. We identified six microRNAs that are potentially specifically involved in metastasis to bone, of which two seem protective and four implicate a higher risk. This aids further understanding of the process of metastasizing to bone. Furthermore, these microRNA hold potential for biomarkers or therapeutic targets. Abstract Bone metastasis in clear-cell renal cell carcinoma (ccRCC) leads to substantial morbidity through skeletal related adverse events and implicates worse clinical outcomes. MicroRNAs (miRNA) are small non-protein coding RNA molecules with important regulatory functions in cancer development and metastasis. In this retrospective analysis we present dysregulated miRNA in ccRCC, which are associated with bone metastasis. In particular, miR-23a-3p, miR-27a-3p, miR-20a-5p, and miR-335-3p specifically correlated with the earlier appearance of bone metastasis, compared to metastasis in other organs. In contrast, miR-30b-3p and miR-139-3p were correlated with less occurrence of bone metastasis. These miRNAs are potential biomarkers and attractive targets for miRNA inhibitors or mimics, which could lead to novel therapeutic possibilities for bone targeted treatment in metastatic ccRCC.
Published: 2021

21. Dense upflow fluidized bed (DUFB) solar receivers of high aspect ratio: Different fluidization modes through inserting bubble rupture promoters

Author: Raf Dewil, Gilles Flamant, Yimin Deng, Jan Baeyens, Renaud Ansart, Alex Le Gal, Shuo Li, Ronny Gueguen, Florian Sabatier, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de génie chimique [ancien site de Basso-Cambo] (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Beijing University of Chemical Technology, University of Western Ontario (UWO), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Beijing University of Chemical Technology - BUCT (CHINA), Katholieke Universiteit Leuven - KU LEUVEN (BELGIUM), Université de Perpignan Via Domitia - UPVD (FRANCE), and Laboratoire de Génie Chimique - LGC (Toulouse, France)
Subjects: Materials science, General Chemical Engineering, Bubble, Particle-in-tube solar receivers, 02 engineering and technology, Heat transfer coefficient, 010402 general chemistry, 01 natural sciences, Industrial and Manufacturing Engineering, [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], Physics::Fluid Dynamics, Bubble rupture promoters, Slugging, Gas through flow, Génie chimique, Environmental Chemistry, Two Fluid Model and sub-grid model, Fluidization, Génie des procédés, Fluidization regimes, ComputingMilieux_MISCELLANEOUS, Turbulence, General Chemistry, Mechanics, Chemical reactor, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Fluidized bed, CFD simulation, Heat transfer, 0210 nano-technology
Abstract: A fluidized bed of Geldart-A particles is promoted as heat transfer fluid in the tubular solar receivers of solar towers. A pressure-driven upward particle flow affects the hydrodynamic flow structure and properties of the fluidized bed. Experiments involved a tube of 0.05 m internal diameter but of very high height/diameter ratio (>120), representative of the future solar receiver and of numerous chemical reactors. Solid circulation fluxes and aeration velocities were varied. Configurations of a bare tube and a tube with bubble rupture promoters were compared. In the bare tube, freely bubbling is transformed into axi-symmetric slugging at a bed level of ~1 m. With bubble rupture promoters, freely bubbling prevails to about a bed level of 3 m, and a turbulent fluidization mode develops higher up the tube (a more chaotic two-phase system with elongated and unstable “gas voids” and “dense solid clusters”), without axi-symmetric slugging detected. Experimental results for both tube configurations were assessed and compared with CFD predictions by the Euler n-fluid code, NEPTUNE_CFD. A good agreement of bed properties was obtained for slug/void frequencies and solids volume fraction in both tube configurations. BRPs moreover enhance the bubble through flow of the fluidizing gas, thus limiting the visible bubble flow rate and bubble sizes while increasing the gas/particle contact, and hence important in designing multi-tube chemical reactors. Whereas slugging limits the heat transfer from the tube wall to the suspension at ~200 W/m2K, the presence of BRPs maintains a heat transfer coefficient in excess of 600 W/m2K.
Published: 2021

22. Reviewing the thermo-chemical recycling of waste polyurethane foam

Author: Yimin Deng, Renaud Ansart, Qian Kang, Jan Baeyens, Raf Dewil, Lise Appels, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de génie chimique [ancien site de Basso-Cambo] (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Beijing University of Chemical Technology, Tianjin Agricultural University (TJAU), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Beijing University of Chemical Technology - BUCT (CHINA), Tianjin Agricultural University - TJAU (CHINA), and Katholieke Universiteit Leuven - KU LEUVEN (BELGIUM)
Subjects: Flue gas, Environmental Engineering, Municipal solid waste, Matériaux, Polyurethane foam, Polyurethanes, Chemical plant, Incineration, 02 engineering and technology, 010501 environmental sciences, Management, Monitoring, Policy and Law, Raw material, Solid Waste, Combustion, 7. Clean energy, 01 natural sciences, 12. Responsible consumption, Thermal insulation, Recycling, Waste Management and Disposal, 0105 earth and related environmental sciences, Waste management, business.industry, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, 6. Clean water, Refuse Disposal, 13. Climate action, Thermal degradation, Environmental science, 0210 nano-technology, business, Thermo-chemical treatment, Syngas
Abstract: International audience; The worldwide production of polymeric foam materials is growing due to their advantageous properties of light weight, high thermal insulation, good strength, resistance and rigidity. Society creates ever increasing amounts of poly-urethane (PU) waste. A major part of this waste can be recycled or recovered in order to be put into further use. The PU industry is committed to assist and play its part in the process. The recycling and recovery of PU foam cover a range of mechanical, physical, chemical and thermo-chemical processes. In addition to the well- documented mechanical and chemical processing options, thermo-chemical treatments are important either as ultimate disposal (incineration) or towards feedstock recovery, leading to different products according to the thermal conditions of the treatment. The review focuses on these thermo-chemical and thermal processes. As far as pyrolysis is concerned, TDI and mostly polyol can be recovered. The highest recovery yields of TDI and polyols occur at low temperatures (150–200 ◦C). It is however clear from literature that pure feedstock will not be produced, and that a further upgrading of the condensate will be needed, together with a thermal or alternative treatment of the non-condensables. Gasification towards syngas has been studied on a larger and industrial scale. Its application would need the location of the PU treatment plant close to a chemical plant, if the syngas is to be valorized or considered in conjunction with a gas-fired CHP plant. Incineration has been studied mostly in a co- firing scheme. Potentially toxic emissions from PU combustion can be catered for by the common flue gas cleaning behind the incineration itself, making this solution less evident as a stand-alone option: the combination with other wastes (such as municipal solid waste) in MSWI′s seems the indicated route to go.
Published: 2021

23. Histidine versus Cysteine-Bearing Heme-Dependent Halogen Peroxidases: Parallels and Differences for Cl– Oxidation

Author: Goedele Roos, Jeremy N. Harvey, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], and Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven]
Subjects: Redox reactions, Oxidation, Bioinorganic chemistry, Peptides and proteins, Ligands, Stereochemistry, Sulfonium, [SDV]Life Sciences [q-bio], 010402 general chemistry, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Materials Chemistry, Reactivity (chemistry), [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Physical and Theoretical Chemistry, Heme, ComputingMilieux_MISCELLANEOUS, Histidine, 030304 developmental biology, 0303 health sciences, Ligand, Porphyrin, Transition state, 0104 chemical sciences, Surfaces, Coatings and Films, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, chemistry, Cysteine
Abstract: International audience; The homodimeric myeloperoxidase (MPO) features a histidine as a proximal ligand and a sulfonium linkage covalently attaching the heme porphyrin ring to the protein. MPO is able to catalyze Cl– oxidation with about the same efficiency as chloroperoxidase at pH 7.0. In this study, we seek to explore the parallels and differences between the histidine and cysteine heme-dependent halogen peroxidases. Transition states, reaction barriers, and relevant thermodynamic properties are calculated on protein models. Together with electronic structure calculations, it gives an overview of the reaction mechanisms and of the factors that determine the selectivity between one- and two-electron paths. Conclusions point to the innate oxidizing nature of MPO with the ester and sulfonium linkages hiking up the reactivity to enable chloride oxidation. The installation of a deprotonated imidazolate as a proximal ligand does not shift the equilibrium from one- to two-electron events without influencing the chemistry of the oxidation reaction.
Published: 2021

24. Integrated membrane bioreactors modelling: A review on new comprehensive modelling framework

Author: Ángel Robles, Christoph Brepols, Joaquim Comas, Jérôme Harmand, Giorgio Mannina, María Victoria Ruano, Jacek Makinia, Taise Ferreira Rebouças, Ignasi Rodríguez-Roda, Giorgio Bertanza, Marc Heran, Marion Alliet, Nesrine Kalboussi, Ilse Smets, Bing-Jie Ni, Mannina G., Alliet M., Brepols C., Comas J., Harmand J., Heran M., Kalboussi N., Makinia J., Robles A., Reboucas T.F., Ni B.-J., Rodriguez-Roda I., Victoria Ruano M., Bertanza G., Smets I., Università degli studi di Palermo - University of Palermo, Laboratoire de Génie Chimique (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Erftverband, Universitat de Girona (UdG), Instituto Catalán de Investigación del Agua - ICRA (SPAIN) (ICRA), Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM), Université de Carthage - University of Carthage, Gdańsk University of Technology (GUT), Departament d'Enginyeria Quimica, Escola Tècnica Superior d'Enginyeria, Universitat de València (UV), University of Technology Sydney (UTS), University of Brescia, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre National de la Recherche Scientifique - CNRS (FRANCE), Erftverband (GERMANY), Ecole Nationale Supérieure de Chimie de Montpellier - ENSCM (FRANCE), Gdansk University of Technology - GUT (POLAND), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut national de recherche pour l'agriculture, l'alimentation et l'environnement - INRAE (FRANCE), Università degli Studi di Brescia (ITALY), University of Technology, Sydney - UTS (AUSTRALIA), Instituto Catalán de Investigación del Agua - ICRA (SPAIN), Université de Carthage (TUNISIA), Universitat de Girona - UdG (SPAIN), Katholieke Universiteit Leuven - KU LEUVEN (BELGIUM), Université de Montpellier (FRANCE), Università degli studi di Palermo (ITALY), Universitat de Valencia - UV (SPAIN), Laboratoire de Génie Chimique, and Laboratoire de Biotechnologie de l'Environnement - LBE (Narbonne, France)
Subjects: 0106 biological sciences, Performance indicators, Computer science, Wastewater treatment, 010501 environmental sciences, Wastewater, Membrane bioreactor, 01 natural sciences, 7. Clean energy, Waste Disposal, Fluid, Bioreactors, Theoretical, Models, 11. Sustainability, Waste Management and Disposal, media_common, [SDE.IE]Environmental Sciences/Environmental Engineering, Waste Disposal, General Medicine, Energy consumption, Biological processes, High environmental sustainability, Modelling framework, Performance indicators, Bioreactors, Membranes, Artificial, Models, Theoretical, Waste Water, Greenhouse Gases, Waste Disposal, Fluid, 6. Clean water, Biological processes, High environmental sustainability, Modelling framework, Membranes, Artificial, Models, Theoretical, Waste Water, Greenhouse Gases, International waters, Artificial, Fluid, Biotechnology, Environmental Engineering, media_common.quotation_subject, Bioengineering, 12. Responsible consumption, 010608 biotechnology, Génie chimique, Quality (business), [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Génie des procédés, 0105 earth and related environmental sciences, Membranes, Settore ICAR/03 - Ingegneria Sanitaria-Ambientale, Renewable Energy, Sustainability and the Environment, Membrane fouling, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 13. Climate action, Greenhouse gas, Sustainability, Biochemical engineering, Performance indicator
Abstract: International audience; Integrated Membrane Bioreactor (MBR) models, combination of biological and physical models, have been representing powerful tools for the accomplishment of high environmental sustainability. This paper, produced by the International Water Association (IWA) Task Group on Membrane Modelling and Control, reviews the state-of-the-art, identifying gaps for future researches, and proposes a new integrated MBR modelling framework. In particular, the framework aims to guide researchers and managers in pursuing good performances of MBRs in terms of effluent quality, operating costs (such as membrane fouling, energy consumption due to aeration) and mitigation of greenhouse gas emissions.
Published: 2021

25. Endothelial CFTR dysfunction and its involvement in the pathogenesis of pulmonary arterial hypertension

Author: Siham Bousfia, Lucas Treps, Peter Witters, Mathias Declercq, Peter Carmeliet, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratory of Angiogenesis and Vascular Metabolism [Leuven, Belgium] (VIB-CCB), Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Cancer Institute [Leuven, Belgium] (LKI), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospitals Leuven [Leuven], Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Pulmonary and Respiratory Medicine, 0303 health sciences, 2019-20 coronavirus outbreak, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, Bioinformatics, Cystic fibrosis, Pulmonary hypertension, 3. Good health, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Mediator, 030228 respiratory system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Nothing, medicine, Familial primary pulmonary hypertension, business, Production team, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Atigny et al. raise interesting points in the transcriptomic analysis of CFTR-impaired endothelial cells (ECs) revealing a pro-inflammatory phenotype [1]. Indeed, CFTR impairment in different endothelial models and organisms, and in the absence of concomitant infection, suggests that ECs are an overlooked mediator in the exaggerated pro-inflammatory phenotype observed in cystic fibrosis (CF). Whether endothelial CFTR is involved in other vascular diseases is an intriguing question. Indeed, a recent report indicates a pivotal role of CFTR in pulmonary arterial hypertension (PAH) [2]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. TREPS has nothing to disclose. Conflict of interest: Siham BOUSFIA has nothing to disclose. Conflict of interest: Dr. Carmeliet has nothing to disclose. Conflict of interest: Dr. Witters has nothing to disclose.
Published: 2021
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26. Towards understanding the extensive diversity of protein N‐glycan structures in eukaryotes

Author: Charlotte Toustou, Marie‐Laure Walet‐Balieu, Marie‐Christine Kiefer‐Meyer, Marine Houdou, Patrice Lerouge, François Foulquier, Muriel Bardor, Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, and Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale [Glyco-MEV]
Subjects: Life Sciences & Biomedicine - Other Topics, glycosylation, CONGENITAL DISORDER, GLYCOLYLNEURAMINIC ACID, N-glycans, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, eukaryotes, Polysaccharides, glycosyltransferases, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], GLYCOSYLATION PATHWAY, Biology, manganese homeostasis, calcium homeostasis, endoplasmic reticulum, Golgi apparatus, regulation, structural diversity, 030304 developmental biology, CARBOHYDRATE CHAINS, 0303 health sciences, Science & Technology, 030302 biochemistry & molecular biology, Eukaryota, MASS-SPECTROMETRY, GLYCOPROTEINS CONTAIN, ASPARAGINE-LINKED OLIGOSACCHARIDES, carbohydrates (lipids), OLIGOMERIC GOLGI-COMPLEX, CAENORHABDITIS-ELEGANS, General Agricultural and Biological Sciences, Life Sciences & Biomedicine, SCHISTOSOMA-MANSONI
Abstract: N-glycosylation is an important post-translational modification of proteins that has been highly conserved during evolution and is found in Eukaryota, Bacteria and Archaea. In eukaryotes, N-glycan processing is sequential, involving multiple specific steps within the secretory pathway as proteins travel through the endoplasmic reticulum and the Golgi apparatus. In this review, we first summarize the different steps of the N-glycan processing and further describe recent findings regarding the diversity of N-glycan structures in eukaryotic clades. This comparison allows us to explore the different regulation mechanisms of N-glycan processing among eukaryotic clades. Recent findings regarding the regulation of protein N-glycosylation are highlighted, especially the regulation of the biosynthesis of complex-type N-glycans through manganese and calcium homeostasis and the specific role of transmembrane protein 165 (TMEM165) for which homologous sequences have been identified in several eukaryotic clades. Further research will be required to characterize the function of TMEM165 homologous sequences in different eukaryotic clades. ispartof: BIOLOGICAL REVIEWS vol:97 issue:2 pages:732-748 ispartof: location:England status: published
Published: 2021

27. Evolutionary novelty in the apoptotic pathway of aphids

Author: Cissy Huygens, Julien Orlans, Patrick Callaerts, Federica Calevro, Nicolas Parisot, Korneel Hens, Mélanie Ribeiro Lopes, Emmanuelle Jousselin, Karen Gaget, Gabrielle Duport, Pieter Baatsen, Sergio Peignier, Pedro da Silva, Hubert Charles, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oxford Brookes University, This work was supported by the Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, INSA (Institut National des Sciences Appliquees), Lyon, the French ANR-16-CE02-0014 (HMicMac) program grant, and KU Leuven grant C14/17/099. INSA-Lyon supported P.C. with an Invited Professorship., ANR-16-CE02-0014,Hmicmac,Co-adaptations hôtes-microbiote: mécanismes et conséquences(2016), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Cellular differentiation, Genome, Insect, PROTEIN, Eye, ANNOTATION, Inhibitor of Apoptosis Proteins, ACTIVATION, Animals, Genetically Modified, 0302 clinical medicine, insects, SPECIFICITY, Caspase, Phylogeny, Genetics, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, Multidisciplinary, biology, Phylogenetic tree, apoptosis, INHIBITOR, food and beverages, IAP, Biological Sciences, Multidisciplinary Sciences, IAPs, Drosophila melanogaster, caspases, Science & Technology - Other Topics, Insect Proteins, EXPRESSION, Programmed cell death, Evolution, Protein domain, PROGRAMMED CELL-DEATH, 03 medical and health sciences, Protein Domains, Animals, 030304 developmental biology, Science & Technology, fungi, PEA APHID, Acyrthosiphon pisum, biology.organism_classification, GENE, Gene Expression Regulation, Aphids, biology.protein, Heterologous expression, 030217 neurology & neurosurgery, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Significance Apoptotic processes play an important role in the development and physiology of almost all metazoan clades. In the highly diverse group of insects, apoptotic pathways have been characterized in only a few dipteran and lepidopteran species, which may not be representative of all insect species. Here, we report the first complete annotation of the apoptotic pathway in a hemipteran insect, the pea aphid Acyrthosiphon pisum. We showed that its apoptotic pathway is rewired compared to other insects, with a significant increase in the number of inhibitors of apoptosis (IAPs) and evidence for functional diversification and structural modularity of this protein family. These novelties are widespread in the aphid lineage, suggesting a yet not understood novel aphid-specific function of IAPs., Apoptosis, a conserved form of programmed cell death, shows interspecies differences that may reflect evolutionary diversification and adaptation, a notion that remains largely untested. Among insects, the most speciose animal group, the apoptotic pathway has only been fully characterized in Drosophila melanogaster, and apoptosis-related proteins have been studied in a few other dipteran and lepidopteran species. Here, we studied the apoptotic pathway in the aphid Acyrthosiphon pisum, an insect pest belonging to the Hemiptera, an earlier-diverging and distantly related order. We combined phylogenetic analyses and conserved domain identification to annotate the apoptotic pathway in A. pisum and found low caspase diversity and a large expansion of its inhibitory part, with 28 inhibitors of apoptosis (IAPs). We analyzed the spatiotemporal expression of a selected set of pea aphid IAPs and showed that they are differentially expressed in different life stages and tissues, suggesting functional diversification. Five IAPs are specifically induced in bacteriocytes, the specialized cells housing symbiotic bacteria, during their cell death. We demonstrated the antiapoptotic role of these five IAPs using heterologous expression in a tractable in vivo model, the Drosophila melanogaster developing eye. Interestingly, IAPs with the strongest antiapoptotic potential contain two BIR and two RING domains, a domain association that has not been observed in any other species. We finally analyzed all available aphid genomes and found that they all show large IAP expansion, with new combinations of protein domains, suggestive of evolutionarily novel aphid-specific functions.
Published: 2020

28. Heat treatment possibilities for an in situ βTi-TiC composite made by laser powder bed fusion

Author: Gang Ji, Haiyang Fan, Sasan Dadbakhsh, Bey Vrancken, Jean-Pierre Kruth, Kim Vanmeensel, Raya Mertens, Ahmed Addad, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Unité Matériaux et Transformations - UMR 8207 (UMET), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centrale Lille Institut (CLIL), European Commission, Region Hauts-de-France, Flanders Innovation & Entrepreneurship agency (Agentschap Innoveren en Ondernemen (VLAIO)) 150010, Region Ile-de-France, Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut National de la Recherche Agronomique (INRA), Université de Lille, CNRS, INRA, ENSCL, Unité Matériaux et Transformations (UMET) - UMR 8207, Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Unité Matériaux et Transformations - UMR 8207 [UMET], Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ANR-16-IDEX-0004,ULNE,ULNE(2016)
Subjects: 0209 industrial biotechnology, Materials science, Additive manufacturing, Whiskers, Composite number, Biomedical Engineering, Laser powder processing, 02 engineering and technology, Industrial and Manufacturing Engineering, [SPI]Engineering Sciences [physics], 020901 industrial engineering & automation, Whisker, General Materials Science, Lamellar structure, Composite material, Ductility, Engineering (miscellaneous), [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Microstructure, Compression (physics), Compressive strength, Heat-treatment, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Titanium alloy, 0210 nano-technology, In situ metal matrix composites
Abstract: After laser powder bed fusion (LPBF) of an ultra-strong in situ TiC whisker reinforced β-Ti composite, this paper investigates the evolution of microstructure and mechanical properties in response to heat treatment at different temperatures. Using in depth nano-SEM and TEM analyses, it is shown that ageing at 400 °C rounds the whiskers, annihilates the strain fields and grows Mo segregated nano-cells, but without improving the ductility. In contrast, ageing at 600 °C enables the transformation of metastable β to a lamellar β + α, leading to a dual phase matrix embedding TiC particles. This is in such a manner that extra ageing at 600 °C coalesces the nano-lamellar α + β microstructure to form a coarser micro-lamellar α + β matrix. This microstructure achieves 66 % of the compressive deformation of Cp-Ti, and over 1400 MPa compressive strength after 1 h of ageing at 600 °C. Despite this success under compression, hard and stiff TiC particles may still cause large spherical fractured voids, severely limiting the plastic deformation under tension. After laser powder bed fusion (LPBF) of an ultra-strong in situ TiC whisker reinforced β-Ti composite, this paper investigates the evolution of microstructure and mechanical properties in response to heat treatment at different temperatures. Using in depth nano-SEM and TEM analyses, it is shown that ageing at 400 °C rounds the whiskers, annihilates the strain fields and grows Mo segregated nano-cells, but without improving the ductility. In contrast, ageing at 600 °C enables the transformation of metastable β to a lamellar β + α, leading to a dual phase matrix embedding TiC particles. This is in such a manner that extra ageing at 600 °C coalesces the nano-lamellar α + β microstructure to form a coarser micro-lamellar α + β matrix. This microstructure achieves 66 % of the compressive deformation of Cp-Ti, and over 1400 MPa compressive strength after 1 h of ageing at 600 °C. Despite this success under compression, hard and stiff TiC particles may still cause large spherical fractured voids, severely limiting the plastic deformation under tension. ispartof: Additive Manufacturing vol:36 status: published
Published: 2020

29. Bio-energy Carriers as Back-up Fuel in Hybrid Solar Power Plants

Author: Jan Baeyens, Renaud Ansart, Yimin Deng, Gilles Flamant, Raf Dewil, Huili Zhang, Shuo Li, Centre National de la Recherche Scientifique - CNRS (FRANCE), European Powder and Process Technology - EPPT (BELGIUM), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Beijing University of Chemical Technology - BUCT (CHINA), Katholieke Universiteit Leuven - KU LEUVEN (BELGIUM), Université de Perpignan Via Domitia - UPVD (FRANCE), Laboratoire Procédés, Matériaux et Energie Solaire - PROMES (Perpignan, France), Beijing University of Chemical Technology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génie chimique [ancien site de Basso-Cambo] (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: Energy carrier, business.industry, 020209 energy, Biomass, 02 engineering and technology, 021001 nanoscience & nanotechnology, Thermal energy storage, 7. Clean energy, Reliability (semiconductor), [CHIM.GENI]Chemical Sciences/Chemical engineering, Hybrid Solar Power, Concentrated solar power, 0202 electrical engineering, electronic engineering, information engineering, Environmental science, Génie chimique, Bio-energy, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Electricity, Fluidized bed combustion, 0210 nano-technology, business, Process engineering, Génie des procédés, Solar power
Abstract: Electricity from concentrated solar power (CSP) plants, gains an increasing interest and importance. To fully match the supply-demand principle, CSP processes include a thermal energy storage and back-up fuel supply. Novel CSP concepts are needed with specific targets of increased efficiency and reliability, and of reduced CAPEX and OPEX. The use of particle suspensions offers significant advantages since applicable in all sub-sections of the complete CSP as heat carrier from the receiver, to the heat storage, and ultimately to the power block. The use of particles in the steam generation (power block) is a common fluidized bed boiler technology. This paper will present the entire particle-based concept, while also discussing the potential to use biomass-based energy carriers as back-up heat supply. Process data and expected effects on the process economy of the system will be discussed.
Published: 2020

30. Signatures of Knowledge for Boolean Circuits under Standard Assumptions (Full version)

Author: Baghery, Karim, González, Alonso, Pindado, Zaira, Ràfols, Carla, Computer Security and Industrial Cryptography [KU Leuven] (ESAT-COSIC), Department of Electrical Engineering [KU Leuven] (KU-ESAT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de l'Informatique du Parallélisme (LIP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Arithmetic and Computing (ARIC), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de l'Informatique du Parallélisme (LIP), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona] (UPF), Abderrahmane Nitaj, Amr Youssef, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), and Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
Subjects: [INFO.INFO-CR]Computer Science [cs]/Cryptography and Security [cs.CR], NIZK, Signatures, Bilinear Groups, CircuitSat NIZK, CircuitSat
Abstract: International audience; This paper constructs unbounded simulation sound proofs for boolean circuit satisfiability under standard assumptions with proof size O(n + d) bilinear group elements, where d is the depth and n is the input size of the circuit. Our technical contribution is to add unbounded simulation soundness to a recent NIZK of González and Ràfols (ASIACRYPT'19) with very small overhead. We give two different constructions: the first one is more efficient but not tight, and the second one is tight. Our new scheme can be used to construct Signatures of Knowledge based on standard assumptions that also can be composed universally with other cryptographic protocols/primitives. As an independent contribution we also detail a simple formula to encode Boolean circuits as Quadratic Arithmetic Programs.
Published: 2020

31. In situ transformations during SLM of an ultra-strong TiC reinforced Ti composite

Author: Sasan Dadbakhsh, Raya Mertens, Kim Vanmeensel, Gang Ji, Jean-Pierre Kruth, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Royal Institute of Technology [Stockholm] (KTH ), Unité Matériaux et Transformations - UMR 8207 (UMET), Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-16-IDEX-0004,ULNE,ULNE(2016), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centrale Lille Institut (CLIL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Department of Mechanical Engineering [Leuven], Université de Lille, CNRS, INRA, ENSCL, Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Royal Institute of Technology [Stockholm] [KTH ], and Unité Matériaux et Transformations - UMR 8207 [UMET]
Subjects: Materials science, Additive manufacturing, Whiskers, Composite number, Alloy, lcsh:Medicine, chemistry.chemical_element, 02 engineering and technology, engineering.material, 01 natural sciences, Article, [SPI]Engineering Sciences [physics], Whisker, Aluminium, 0103 physical sciences, Selective laser melting, Composite material, lcsh:Science, Ductility, Powder mixture, 010302 applied physics, Multidisciplinary, Synthesis and processing, lcsh:R, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, chemistry, engineering, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], In situ alloying-reinforcing, Metal matrix composites, lcsh:Q, Titanium alloy, Powder laser processing, 0210 nano-technology, Biomedical engineering
Abstract: This work demonstrates a successful in situ method capable of producing an ultra-strong novel Ti composite without aluminium and vanadium. In this method, selective laser melting is used to conduct in situ alloying and reinforcing of a Ti/10.5 wt% Mo2C powder mixture. It is shown that this leads to a metastable β-Ti matrix homogeneously reinforced by high aspect ratio, 50–200 nm wide and up to several micrometre long TiC whiskers. The transformations of the phases are controlled by decomposition, dissolution, diffusion, and reformation of constituents. The whisker morphology of in situ formed TiC particles is associated with directional crystal growth along the TiC direction. The developed TiC reinforced β-Ti alloy combines a hardness over 500 HV, a Young’s modulus of 126 GPa, and an ultimate compressive strength of 1642 MPa. Improving the ductility of this composite is the subject of another work.
Published: 2020

32. Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer

Author: Samira Majjaj, Christine Desmedt, Gert Van den Eynden, Julien Pingitore, Denis Larsimont, Elia Biganzoli, Diether Lambrechts, Françoise Rothé, François Bertucci, Florian Clatot, Giancarlo Pruneri, Odette Mariani, Caterina Marchiò, Bram Boeckx, Roberto Salgado, Francois Richard, Christos Sotiriou, David Venet, Anne Vincent-Salomon, Christine Galant, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université libre de Bruxelles (ULB), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Università degli studi di Torino = University of Turin (UNITO), Candiolo Cancer Institute (IRCCS), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Cliniques Universitaires Saint-Luc [Bruxelles], AZ Sint-Augustinus, 2610 Wilrijk, Università degli Studi di Milano = University of Milan (UNIMI), European Institute of Oncology [Milan] (ESMO), IRCCS Istituto Nazionale dei Tumori [Milano], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: 0301 basic medicine, Cancer Research, ARID1A, Receptor, ErbB-2, Estrogen receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Metastasis, CDH1, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Lymphocytes, Tumor-Infiltrating, medicine, Biomarkers, Tumor, PTEN, Humans, Stromal tumor, skin and connective tissue diseases, neoplasms, Retrospective Studies, biology, business.industry, Carcinoma, Ductal, Breast, Médecine pathologie humaine, Genomics, Sciences bio-médicales et agricoles, Middle Aged, medicine.disease, Prognosis, Cancérologie, body regions, Survival Rate, Carcinoma, Lobular, 030104 developmental biology, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Invasive lobular carcinoma, Lymphatic Metastasis, Mutation, biology.protein, Cancer research, Female, Stromal Cells, business, Receptors, Progesterone, Follow-Up Studies
Abstract: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level., info:eu-repo/semantics/published
Published: 2020

33. The Added Value of Longitudinal Imaging for Preclinical In vivo Efficacy Testing of Therapeutic Compounds against Cerebral Cryptococcosis

Author: Uwe Himmelreich, Jennifer Poelmans, Greetje Vande Velde, Amy Hillen, Matthias Brock, Liesbeth Vanherp, Guilhem Janbon, Katrien Lagrou, Biomedical MRI [Leuven], Department of Imaging and Pathology [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), core facility Molecular Small Animal Imaging Center (Leuven) (MoSAIC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris] (IP), School of Life Sciences, University of Nottingham, UK (UON), Laboratory of Clinical Bacteriology and Mycology [Leuven], Department of Microbiology, Immunology and Transplantation [Leuven], Centre national de référence pour les mycoses [Leuven], University Hospitals Leuven [Leuven], This work was funded by the European ERA-NET project ‘CryptoView’ (3rd call of the FP7 program Infect-ERA), the Research Foundation-Flanders (FWO, 1506114N) and KU Leuven (PF 10/017 (IMIR), CREA/14/015). L.V. is a PhD fellow strategic basic research at the FWO (151313). J.P. received a PhD grant for strategic basic research from the Agency for Innovation by Science and Technology (IWT, 141230). G.V.V. received a postdoctoral fellowship from the FWO (12N7615N)., European Project: 321529,EC:FP7:HEALTH,FP7-ERANET-2012-RTD,INFECT-ERA(2013), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Pharmacology, Postmortem studies, medicine.diagnostic_test, business.industry, 030106 microbiology, Bioinformatics, medicine.disease, 3. Good health, Efficacy, 03 medical and health sciences, 030104 developmental biology, Infectious Diseases, Drug development, In vivo, Cryptococcosis, Magnetic resonance imaging of the brain, Medicine, Bioluminescence imaging, Pharmacology (medical), business, Preclinical imaging, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: The authors wish to thank Jens Wouters and Sarah Belderbos for their assistance and thank Dr. Kristof Govaerts for his guidance with the MRI quantification. We gratefully acknowledge Dr. Steffen Fieuws (L-BioStat, KU Leuven) for statistical advice.; International audience; Brain infections with Cryptococcus neoformans are associated with significant morbidity and mortality. Cryptococcosis typically presents as meningoencephalitis or fungal mass lesions called cryptococcomas. Despite frequent in vitro discoveries of promising novel antifungals, the clinical need for drugs that can more efficiently treat these brain infections remains. A crucial step in drug development is the evaluation of in vivo drug efficacy in animal models. This mainly relies on survival studies or post-mortem analyses in large groups of animals, but these techniques only provide information on specific organs of interest at predefined time points. In this proof-of-concept study, we validated the use of non-invasive preclinical imaging to obtain longitudinal information on the therapeutic efficacy of amphotericin B or fluconazole monotherapy in meningoencephalitis and cryptococcoma mouse models. Bioluminescence imaging (BLI) enabled the rapid in vitro and in vivo evaluation of drug efficacy while complementary high-resolution anatomical information obtained by magnetic resonance imaging (MRI) of the brain allowed a precise assessment of the extent of infection and lesion growth rates. We demonstrated a good correlation between both imaging readouts and the fungal burden in various organs. Moreover, we identified potential pitfalls associated with the interpretation of therapeutic efficacy based solely on post-mortem studies, demonstrating the added value of this non-invasive dual imaging approach compared to standard mortality curves or fungal load endpoints. This novel preclinical imaging platform provides insights in the dynamic aspects of the therapeutic response and facilitates a more efficient and accurate translation of promising antifungal compounds from bench to bedside.
Published: 2020

34. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer

Author: Duncan Graham, Paul Peixoto, Mélanie Planque, Mark Salji, Karen Faulds, Hing Y. Leung, Ernest Mui, Catriona A. Ford, David Sumpton, Giovanny Rodriguez Blanco, Colin Nixon, Luke Gaughan, Sara Zanivan, Chara Ntala, Sergio Lilla, Elke Markert, Gillian M. Mackay, Rachana Patel, Jurre J. Kamphorst, Peter Repiscak, Arnaud Blomme, Grace McGregor, Lauren E. Jamieson, Sarah-Maria Fendt, Eric Hervouet, Cancer Research UK Beatson Institute [Glasgow], University of Glasgow, University of Strathclyde [Glasgow], Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), EPIgenetics and GENe EXPression Technical Plateform (EPIGENExp), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Dispositif Inter-régional d'Imagerie Cellulaire [Dijon] (DImaCell), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Newcastle University [Newcastle], This work was supported by Cancer Research UK Beatson Institute core funding (C596/A17196) and CRUK core group awarded to HYL (A15151) and to SZ (A12935). P.P. and E.H. were funded by grants from 'La ligue Contre le Cancer', 'la région Bourgogne Franche-Comté' and 'Canceropole Grand Est'. M.S. is a Medical Research Council Clinical Research Fellow (MR/L017997/1). C.N. is the recipient of CRUK Clinical Research Fellowship (grant 300444-01). D.G. and K.F. acknowledge support from the EPSRC grant EP/L014165/1 that supported L.J. S.-M.F. acknowledges FWO funding and KU Leuven Methusalem co-funding., Bodescot, Myriam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Agroécologie [Dijon], and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Proteomics, 0301 basic medicine, General Physics and Astronomy, Reductase, urologic and male genital diseases, Prostate cancer, 0302 clinical medicine, Homeostasis, QD, lcsh:Science, Phospholipids, Multidisciplinary, Chemistry, Prostate, Cancer metabolism, Phenotype, Mitochondria, 3. Good health, Prostatic Neoplasms, Castration-Resistant, Receptors, Androgen, 030220 oncology & carcinogenesis, Disease Progression, Oxidoreductases Acting on CH-CH Group Donors, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, General Biochemistry, Genetics and Molecular Biology, RC0254, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, LNCaP, Androgen Receptor Antagonists, medicine, Humans, Metabolomics, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Lipid metabolism, General Chemistry, Lipid Metabolism, medicine.disease, Androgen receptor, 030104 developmental biology, Lipidomics, Unfolded protein response, Cancer research, lcsh:Q
Abstract: Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multiple AR inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant cells and associated with perturbed glucose and lipid metabolism. To exploit this phenotype, we delineate a subset of proteins consistently associated with ARI resistance and highlight mitochondrial 2,4-dienoyl-CoA reductase (DECR1), an auxiliary enzyme of beta-oxidation, as a clinically relevant biomarker for CRPC. Mechanistically, DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises CRPC cells to ferroptosis. In vivo, DECR1 deletion impairs lipid metabolism and reduces CRPC tumour growth, emphasizing the importance of DECR1 in the development of treatment resistance., Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.
Published: 2020

35. A Feed-Forward Mechanosignaling Loop Confers Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutant Melanoma

Author: Aude Mallavialle, Sébastien Schaub, Marcel Deckert, Virginie Prod'homme, Christophe Girard, Frédéric Larbret, Stéphane Audebert, Rania Ben Jouira, Margaux Lecacheur, Bernard Mari, Berestjuk I, Serena Diazzi, Maeva Gesson, Jean-Christophe Marine, Sophie Tartare-Deckert, Sabrina Pisano, Eleonora Leucci, Cedric Gaggioli, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institute of Developmental Biology and Cancer (IBDC), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratory for Molecular Cancer Biology, Flanders Institute for Biotechnology, Ghent University [Belgium] (UGENT), Lecacheur, M, Ben Jouira, Rania, Berestjuk, Ilona, Diazzi, S, Prod’homme, V, Mallavialle, Aude, Larbret, Frédéric, Gesson, Maéva, Schaub, Sébastien, Pisano, S, Audebert, Stéphane, Mari, Bernard, Gaggioli, Cédric, Leucci, E, Marine, Jean-Christophe, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), ANR-18-CE14-0019,INFLAMMASYK,Etude de la signalisation SYK dans les maladies inflammatoires chroniques(2018), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and TARTARE-DECKERT, Sophie
Subjects: Proto-Oncogene Proteins B-raf, 0301 basic medicine, MAPK/ERK pathway, Cancer Research, MAP Kinase Signaling System, extracellular matrix, [SDV]Life Sciences [q-bio], Cell, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Extracellular matrix, resistance, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, MRTF, Tumor Microenvironment, medicine, melanoma, Animals, Humans, Autocrine signalling, Protein Kinase Inhibitors, Transcription factor, ComputingMilieux_MISCELLANEOUS, Chemistry, Melanoma, Mesenchymal stem cell, medicine.disease, Xenograft Model Antitumor Assays, targeted therapies, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Cancer research, YAP, Reprogramming
Abstract: Aberrant extracellular matrix (ECM) deposition and stiffening is a physical hallmark of several solid cancers and is associated with therapy failure. BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that is frequently associated with transcriptional reprogramming and a de-differentiated cell state. Melanoma cells secrete their own ECM proteins, an event that is promoted by oncogenic BRAF inhibition. Yet, the contribution of cancer cell–derived ECM and tumor mechanics to drug adaptation and therapy resistance remains poorly understood. Here, we show that melanoma cells can adapt to targeted therapies through a mechanosignaling loop involving the autocrine remodeling of a drug-protective ECM. Analyses revealed that therapy-resistant cells associated with a mesenchymal dedifferentiated state displayed elevated responsiveness to collagen stiffening and force-mediated ECM remodeling through activation of actin-dependent mechanosensors Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF). Short-term inhibition of MAPK pathway also induced mechanosignaling associated with deposition and remodeling of an aligned fibrillar matrix. This provided a favored ECM reorganization that promoted tolerance to BRAF inhibition in a YAP- and MRTF-dependent manner. Matrix remodeling and tumor stiffening were also observed in vivo upon exposure of BRAF-mutant melanoma cell lines or patient-derived xenograft models to MAPK pathway inhibition. Importantly, pharmacologic targeting of YAP reversed treatment-induced excessive collagen deposition, leading to enhancement of BRAF inhibitor efficacy. We conclude that MAPK pathway targeting therapies mechanically reprogram melanoma cells to confer a drug-protective matrix environment. Preventing melanoma cell mechanical reprogramming might be a promising therapeutic strategy for patients on targeted therapies. Significance: These findings reveal a biomechanical adaptation of melanoma cells to oncogenic BRAF pathway inhibition, which fuels a YAP/MRTF-dependent feed-forward loop associated with tumor stiffening, mechanosensing, and therapy resistance.
Published: 2020

36. Landau theory for non-equilibrium steady states

Author: Camille Aron, Claudio Chamon, Champs Aléatoires et Systèmes hors d'Équilibre, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institute for Theoretical Physics, KULeuven, Institute for Theoretical Physics, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Physics [Boston], Boston University [Boston] (BU), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: Physics, [PHYS]Physics [physics], Statistical Mechanics (cond-mat.stat-mech), General Physics and Astronomy, Single bath, FOS: Physical sciences, 01 natural sciences, lcsh:QC1-999, Landau theory, 010305 fluids & plasmas, Mean field theory, Harmonics, Quantum electrodynamics, 0103 physical sciences, Density of states, Condensed Matter::Statistical Mechanics, Continuous phase transition, [PHYS.COND.CM-SM]Physics [physics]/Condensed Matter [cond-mat]/Statistical Mechanics [cond-mat.stat-mech], 010306 general physics, Critical exponent, lcsh:Physics, Energy (signal processing), Condensed Matter - Statistical Mechanics
Abstract: We examine how systems in non-equilibrium steady states close to a continuous phase transition can still be described by a Landau potential if one forgoes the assumption of analyticity. In a system simultaneously coupled to several baths at different temperatures, the non-analytic potential arises from the different density of states of the baths. In periodically driven-dissipative systems, the role of multiple baths is played by a single bath transferring energy at different harmonics of the driving frequency. The mean-field critical exponents become dependent on the low-energy features of the two most singular baths. We propose an extension beyond mean field., Comment: 18 pages. v2: minor edits
Published: 2020

37. Discussion on the Figures of Merit of Identified Traps Located in the Si Film: Surface Versus Volume Trap Densities

Author: Geert Hellings, Bogdan Cretu, Beya Nafaa, Cor Claeys, Dimitri Linten, Eddy Simoen, Equipe Electronique - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), IMEC (IMEC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), IMEC, and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)
Subjects: Condensed Matter::Quantum Gases, 010302 applied physics, Surface (mathematics), Work (thermodynamics), Materials science, 02 engineering and technology, 021001 nanoscience & nanotechnology, Plateau (mathematics), 01 natural sciences, Trap (computing), [SPI]Engineering Sciences [physics], Volume (thermodynamics), Depletion region, 0103 physical sciences, MOSFET, Figure of merit, Atomic physics, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS
Abstract: In this work a discussion on the estimated volume trap densities (NT) compared to surface traps densities (Neff) related to identified traps in the Si fin of Si/SiGe superlattice I/O n-channel FinFETs using low frequency noise spectroscopy is made. The investigated devices present a fin width of 10 nm, a fin height of 10 nm and four fins in parallel, leading to an equivalent channel width of 120 nm. The equivalent oxide thickness (EOT) is 5.6 nm. More details on the device fabrication and experimental setup may be found in [1,2]. The noise spectra and the estimated surface traps densities are provided in [3]. In this work, focus is only on the identified T4 trap, for which using the linear dependence that should exist between A0i and t0i related to the same trap, without any other assumption, a surface trap density of 2.8∙1012cm-2 is obtained [3]. It should be noted that from the 1/f flat-band noise level an interface trap density value of about 1.9∙1018 eV-1cm-3 is obtained at 300 K. However, as the traps in the Si film are related to a volume phenomenon, two methodologies to estimate the volume trap densities are employed: one using the relationship between the surface trap density and volume trap densitiy [4], where B is a coefficient estimated to be 1/3 [4,5]; and a second one from the temperature (T) evolution at fixed frequency of the Lorentzian plateau level associated to the same trap (from equation 34 in [4]). Using the first method leads to a volume trap density of T4 of about 1.7∙1019 cm-3. The second method consists to use the maximum of the measured Svg_Lor(f 0,T) dependence with temperature. Indeed, the Svg_Lor(f 0,T) of Lorentzians associated to the same trap are proportional with ti(T)/{1 + [2pf 0ti(T)]2}. For a given frequency f 0, if 2pf 0ti(T) ≫ 1, SVg_Lor(f 0,T) ∝ ti(T)]-1, and SVg_Lor(f 0,T) increases with increasing temperature because ti decreases. If 2pf 0ti(T) ≪ 1, then SVg_Lor(f 0,T) ∝ ti(T) and SVg_Lor(f 0,T) decreases with increasing temperature, as explained in detail in [4]. The evolution of the Svg_Lor(f 0,T)∙f 0 in a temperature range where T4 traps are active is illustrated in Figure 1 and presents a bell-shaped behavior, as expected. Using this method, volume trap densities of about 1.25∙1018 cm-3 for f 0 = 10 kHz and of about 1.1∙1018 cm-3 for f 0 = 14 kHz are obtained. It may be observed that the estimated volume trap densities of the T4 defect are about one decade lower than when using the first method. This overestimation by the first method is related to the fact that the theoretical B coefficient was determined for conventional planar devices with one gate [4,5]. Moreover, it may be noticed that the second method is dependent on the fixed f 0 selected. The paper will present a discussion with more details, considering all identified traps in [1] and considering additional new low frequency noise spectroscopy results. References : [1] Hellings, H. Mertens, A. Subirats, E. Simoen, T. Schram, L.-A. Ragnarsson et al., “Si/SiGe superlattice I/O finFETs in a vertically-stacked Gate-All-Around horizontal Nanowire Technology”, in Tech. Dig. Symp. on VLSI Technology, The IEEE New York, 2018, p.p. 85-86, DOI: 10.1109/VLSIT.2018.8510654. [2] Boudier, B. Cretu, E. Simoen, R. Carin, A. Veloso, N. Collaert, and A. Thean, “Low frequency noise assessment in n- and p-channel sub-10 nm triple-gate FinFETs: Part I: Theory and methodology,” Solid State Electron., vol. 128, pp. 102-108, 2017, DOI: 10.1016/j.sse.2016.10.012. [3] Boudier, B. Cretu, E. Simoen, G. Hellings, T. Schram, H. Mertens and D. Linten, “Low frequency noise analysis on Si/SiGe superlattice I/O n-channel FinFETs”, In Proceedings of EUROSOI-ULIS’2019. [4] Lukyanchikova, “Noise and Fluctuations Control in Electronic Device”, edited by A. Balandin, American Scientific, Riverside, CA, 2002, pp. 201-233. [5] Yau and C-T. Sah, “Theory and experiments of low-frequency generation-recombination noise in MOS transistors”, IEEE Trans. Electron Dev., 1969, vol.16, pp. 170-177. Figure 1 : SVg_Lor(f 0,T)·f 0 versus temperature for the T4 trap identified in [3]; on the secondary Oy axis the characteristic frequency f 0i of the Lorentzians is displayed in function of temperature. Figure 1
Published: 2020

38. Blind deconvolution of fundamental and harmonic ultrasound images

Author: Giulia Matrone, Jean-Yves Tourneret, Oleg V. Michailovich, Adrian Basarab, Alessandro Ramalli, Denis Kouame, Mohamad Hourani, CoMputational imagINg anD viSion (IRIT-MINDS), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), University of Waterloo [Waterloo], Università degli Studi di Pavia, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut National Polytechnique (Toulouse) (Toulouse INP), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), Katholieke Universiteit Leuven - KU LEUVEN (BELGIUM), University of Waterloo (CANADA), and Università di Pavia (ITALY)
Subjects: Blind deconvolution, Point spread function, Scattering, Computer science, business.industry, Ultrasound, Harmonic ultrasound imaging, Function (mathematics), Inverse problem, 01 natural sciences, Image (mathematics), Convolution, Image restoration, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, 0103 physical sciences, Ultrasound imaging, Harmonic, Traitement du signal et de l'image, business, 010301 acoustics, Algorithm
Abstract: International audience; Restoring the tissue reflectivity function (TRF) from ultrasound (US) images is an extensively explored research field. It is well-known that human tissues and contrast agents have a non-linear behavior when interacting with US waves. In this work, we investigate this non-linearity and the interest of including harmonic US images in the TRF restoration process. Therefore, we introduce a new US image restoration method taking advantage of the fundamental and harmonic components of the observed radiofrequency (RF) image. The depth information contained in the fundamental component and the good resolution of the harmonic image are combined to create an image with better properties than the fundamental and harmonic images considered separately. Under the hypothesis of weak scattering, the RF image is modeled as the 2D convolution between the TRF and the system point spread function (PSF). An inverse problem is formulated based on this model able to jointly estimate the TRF and the PSF. The interest of the proposed blind deconvolution algorithm is shown through an in vivo result and compared to a conventional US restoration method.
Published: 2020

39. National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Author: NCD Risk Factor Collaboration (NCD-RisC), [missing], Taddei, Cristina, Jackson, Rod, Zhou, Bin, Bixby, Honor, Danaei, Goodarz, Di Cesare, Mariachiara, Kuulasmaa, Kari, Hajifathalian, Kaveh, Bentham, James, Bennett, James E, Aekplakorn, Wichai, Cifkova, Renata, Dallongeville, Jean, DeBacquer, Dirk, Giampaoli, Simona, Gudnason, Vilmundur, Khang, Young-Ho, Laatikainen, Tiina, Mann, JimI, Marques-Vidal, Pedro, Mensah, George A, Müller-Nurasyid, Martina, Ninomiya, Toshiharu, Petkeviciene, Janina, Rodríguez-Artalejo, Fernando, Servais, Jennifer, Söderberg, Stefan, Stavreski, Bill, Wilsgaard, Tom, Zdrojewski, Tomasz, Zhao, Dong, Stevens, Gretchen A, Savin, Stefan, Cowan, Melanie J, Riley, Leanne M, Ezzati, Majid, Adams, Robert J, Ahrens, Wolfgang, Amouyel, Philippe, Amuzu, Antoinette, Anderssen, Sigmund A, Ariansen, Inger, Arveiler, Dominique, Aspelund, Thor, Auvinen, Juha, Avdicová, Mária, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Barbagallo, Carlo M, Bata, Iqbal, Baur, Louise A, Beaglehole, Robert, Bernotiene, Gailute, Bi, Yufang, Bienek, Asako, Björkelund, Cecilia, Bo, Simona, Boehm, Bernhard O, Bonaccio, Marialaura, Bongard, Vanina, Borchini, Rossana, Borghs, Herman, Breckenkamp, Juergen, Brenner, Hermann, Bruno, Graziella, Busch, Markus A, Cabrera de León, Antonio, Capuano, Vincenzo, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Censi, Laura, Chen, Fangfang, Chen, Shuohua, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Chudek, Jerzy, Claessens, Frank, Clarke, Janine, Clays, Els, Cooper, Cyrus, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Crujeiras, Ana B, Cui, Liufu, D'Arrigo, Graziella, Dauchet, Luc, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, De Smedt, Delphine, Dennison, Elaine, Deschamps, Valérie, DiCastelnuovo, Augusto, Dobson, Annette J, Donfrancesco, Chiara, Döring, Angela, Drygas, Wojciech, Du, Yong, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, Elosua, Roberto, Eriksson, Johan G, Evans, Alun, Faeh, David, Felix-Redondo, Francisco J, Fernández-Bergés, Daniel, Ferrari, Marika, Ferrieres, Jean, Finn, Joseph D, Forslund, Ann-Sofie, Forsner, Maria, Frontera, Guillermo, Fujita, Yuki, Gaciong, Zbigniew, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goltzman, David, GonzalezGross, Marcela, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Gregor, Ronald D, Grodzicki, Tomasz, Grosso, Giuseppe, Gruden, Grabriella, Gu, Dongfeng, Guallar-Castillón, Pilar, Gudmundsson, Elias F, Guessous, Idris, Gunnlaugsdottir, Johanna, Gutzwiller, Felix, Hardy, Rebecca, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J, He, Jiang, He, Yuna, Herrala, Sauli, TapaniHihtaniemi, Ilpo, Hobbs, Michael, Hopman, Wilma M, MaríaHuerta, José, Huybrechts, Inge, Iacoviello, Licia, Iannone, Anna G, Ikeda, Nayu, Iwasaki, Masanori, Jamrozik, Konrad, Janszky, Imre, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jennings, Garry, Jeong, Seung-lyeal, QiangJiang, Chao, Joffres, Michel, Jokelainen, Jari J, Jonas, Jost B, Jóźwiak, Jacek, Kajantie, Eero O, Kauhanen, Jussi, Keil, Ulrich, Keinänen-Kiukaanniemi, Sirkka, Kersting, Mathilde, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Ko, Stephanie, Kolle, Elin, Korpelainen, Raija, Koskinen, Seppo, Kouda, Katsuyasu, Kratzer, Wolfgang, Kriemler, Susi, Krokstad, Steinar, Kujala, Urho M, Kurjata, Pawel, HingLam, Tai, Lanska, Vera, Lappas, Georg, Laugsand, Lars E, Lee, Jeonghee, Lehtimäki, Terho, Li, Yanping, Lilly, Christa L, Lin, Xu, Lind, Lars, Lissner, Lauren, Liu, Jing, Lopez-Garcia, Esther, Lorbeer, Roberto, EugenioLozano, José, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lytsy, Per, Ma, Guansheng, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Manzato, Enzo, Mathiesen, Ellisiv B, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, Meirhaeghe, Aline, Meisinger, Christa, Metcalf, Patricia, Mi, Jie, Miller, Jody C, Moreno, Luis A, Morin, Suzanne, Mossakowska, Malgorzata, Muiesan, Maria L, Mursu, Jaakko, Nakamura, Harunobu, Námešná, Jana, Nauck, Matthias, MariaNavarrete-Muñoz, Eva, Neal, William A, Nenko, Ilona, Niiranen, Teemu J, Ning, Guang, Noale, Marianna, Norie, Sawada, Noto, Davide, O'Neill, Terence, O'Reilly, Dermot, Oh, Kyungwon, Olafsson, Örn, MichelPaccaud, Fred, Pajak, Andrzej, Palmieri, Luigi, Panza, Francesco, Parnell, Winsome R, Peltonen, Markku, Peters, Annette, Petersmann, Astrid, Pigeot, Iris, Pilotto, Lorenza, Piwonska, Aleksandra, Plans-Rubió, Pedro, Porta, Miquel, Price, Jacqueline F, Puder, Jardena J, Puhakka, Soile E, Radisauskas, Ricardas, Raitakari, Olli, Ramos, Rafel, Redon, Josep, Rigo, Fernando, Rodriguez-Perez, MaríadelCristo, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Ruidavets, Jean-Bernard, Rutkowski, Marcin, Salanave, Benoit, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sans, Susana, Saramies, Jouko L, Saum, Kai-Uwe, Scheidt-Nave, Christa, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Sebert, Sylvain, Sen, Abhijit, Shaw, Jonathan E, Shibuya, Kenji, WookShin, Dong, Shiri, Rahman, Simons, Judith, Simons, Leon A, Sjöström, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Solfrizzi, Vincenzo, Sonestedt, Emily, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Steene-Johannessen, Jostein, Stehle, Peter, Stieber, Jutta, Stöckl, Doris, Stokwiszewski, Jakub, Sundström, Johan, Suriyawongpaisal, Paibul, Tamosiunas, Abdonas, JooTan, Eng, Taylor, Anne, Tell, Grethe, Thijs, Lutgarde, Tolonen, HannaK, Topór-Madry, Roman, JoséTormo, María, Torrent, Maties, Tsugane, Shoichiro, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Tzourio, Christophe, Uusitalo, Hannu M T, Van Herck, Koen, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Veronesi, Giovanni, Vioque, Jesus, Virtanen, JyrkiK, Visvikis-Siest, Sophie, Vollenweider, Peter, Voutilainen, Sari, Vrijheid, Martine, Wagner, Aline, Wagner, Anne, Wang, Ming-Dong, Wang, Qian, XingWang, Ya, Wannamethee, S Goya, Wei, Wenbin, Whincup, Peter H, Wiecek, Andrzej, Willeit, Johann, Willeit, Peter, Wojtyniak, Bogdan, Wong, Andrew, Woodward, Mark, GiwercmanWu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yoshihara, Akihiro, Zambon, Sabina, Zhao, Wenhua, Imperial College London, University of Auckland [Auckland], Harvard T.H. Chan School of Public Health, Middlesex University, National Institute for Health and Welfare [Helsinki], Weill Medical College of Cornell University [New York], University of Kent [Canterbury], Mahidol University [Bangkok], Charles University [Prague] (CU), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Universiteit Gent = Ghent University [Belgium] (UGENT), Istituto Superiore di Sanita [Rome], Icelandic Heart Association [Kopavogur, Iceland] (IHA), Seoul National University [Seoul] (SNU), University of Otago [Dunedin, Nouvelle-Zélande], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Helmholtz-Zentrum München (HZM), Kyushu University [Fukuoka], Universidad Autonoma de Madrid (UAM), CIBER de Epidemiología y Salud Pública (CIBERESP), Umeå University, The Arctic University of Norway (UiT), Medical University of Gdańsk, Capital University of Medical Sciences [Beijing] (CUMS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Adelaide, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), London School of Hygiene and Tropical Medicine (LSHTM), Norwegian School of Sport Sciences = Norges idrettshøgskole [Oslo] (NIH), Norwegian Institute of Public Health [Oslo] (NIPH), Université de Strasbourg (UNISTRA), University of Iceland [Reykjavik], University of Oulu, Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], Medical University of Łódź (MUL), Università degli studi di Palermo - University of Palermo, Dalhousie University [Halifax], The University of Sydney, Public Health Agency of Canada, University of Gothenburg (GU), University of Turin, Nanyang Technological University [Singapour], Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Universität Bielefeld = Bielefeld University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Robert Koch Institute [Berlin] (RKI), Universidad de La Laguna [Tenerife - SP] (ULL), Universidade de Santiago de Compostela [Spain] (USC ), University College of London [London] (UCL), University of Silesia in Katowice, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Southampton, Biomolécules et inflammation pulmonaire, Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Santé publique France - French National Public Health Agency [Saint-Maurice, France], University of Queensland [Brisbane], IMIM-Hospital del Mar, Generalitat de Catalunya, Queen's University [Belfast] (QUB), Universität Zürich [Zürich] = University of Zurich (UZH), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Manchester [Manchester], Kindai University, Medical University of Warsaw - Poland, Università degli studi di Catania [Catania], Geneva University Hospital (HUG), Universitá degli Studi dell’Insubria, McGill University = Université McGill [Montréal, Canada], Universidad Politécnica de Madrid (UPM), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Clinical and Experimental Medicine (IKEM), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Bergen (UiB), Tulane University, Chinese Center for Disease Control and Prevention, Oulu University Hospital [Oulu], The University of Western Australia (UWA), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Niigata University, Norwegian University of Science and Technology (NTNU), Simon Fraser University (SFU.ca), University of Eastern Finland, Westfälische Wilhelms-Universität Münster (WWU), Innsbruck Medical University [Austria] (IMU), Universitätsklinikum Ulm - University Hospital of Ulm, University of Jyväskylä (JYU), The University of Hong Kong (HKU), Sahlgrenska Academy at University of Gothenburg [Göteborg], Tampere University Hospital, University of Tampere [Finland], West Virginia University [Morgantown], University of Chinese Academy of Sciences [Beijing] (UCAS), Uppsala Universitet [Uppsala], Universität Greifswald - University of Greifswald, Peking University [Shenzhen], The Jikei University School of Medicine, Baker Heart and Diabetes Institute (AUSTRALIA), Universita degli Studi di Padova, University of Edinburgh, University of Zaragoza - Universidad de Zaragoza [Zaragoza], International Institute of Molecular and Cell Biology [Warsaw] (IIMCB), Università degli Studi di Brescia [Brescia], Konan University [Kobe, Japan], University of Turku, Shanghai Jiao Tong University School of Medicine, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Department of Epidemiology, Health Economics and Public Health, UMR 558 INSERM, Université de Toulouse, Centre Hospitalier Universitaire de Toulouse, Unité de Surveillance et d'Epidémiologie Nutritionnelle (USEN), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Université Paris 13 (UP13), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Department of Reproductive Endocrinology, University of Bari Aldo Moro (UNIBA), Nutritional Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Applied Food Science, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Research Unit Hypertension and Cardiovascular Epidemiology [Louvain, Belgique], Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National Cancer Center, University of Kuopio, Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Tampere University, Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Departamento de Salud Pública, Universidad Miguel Hernández [Elche] (UMH), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Department of Internal Medicine, School of Public Health and Clinical Nutrition, Epidemiologia Ambiental, Centre for Research in Environmental Epidemiology (CREAL)-Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP) of Pamplona-Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Department of Epidemiology and Public Health, EA 3430, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Medical University of Silesia (SUM), University of Innsbruck, National Institute of Hygiene Warsaw, The Georges Institute for International Health, Naval Research Laboratory (NRL), Grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z, Ministry of Health of the Czech Republic (grant number 15-27109A), UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, HUS Children and Adolescents, Department of Public Health, Universidad Autónoma de Madrid (UAM), Università degli studi di Torino = University of Turin (UNITO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), CHU Toulouse [Toulouse], Université Paris 13 (UP13)-Institut de Veille Sanitaire (INVS)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), Taddei, C, Zhou, B, Bixby, H, Danaei, G, Di Cesare, M, Kuulasmaa, K, Hajifathalian, K, Bentham, J, Bennett, JE, Aekplakorn, W, Cifkova, R, Dallongeville, J, DeBacquer, D, Giampaoli, S, Gudnason, V, Khang, Y-O, Laatikainen, T, Mann, JI, Marques-Vidal, P, Mensah, GA, Müller-Nurasyid, M, Ninomiya, T, Petkeviciene, J, Rodríguez-Artalejo, F, Servais, J, Söderberg, S, Stavreski, B, Wilsgaard, T, Zdrojewski, T, Zhao, D, Stevens, GA, Savin, S, Cowan, Mj, Riley, LM, Ezzati, M, Adams, R, Ahrens, W, Amouyel, P, Amuzu, A, Anderssen, SA, Ariansen, I, Arveiler, D, Aspelund, T, Auvinen, A, Avdicová, M, Banach, M, Bandosz, P, Banegas. JR, Barbagallo, CM, Bata, I, Baur, LA, Beaglehole, R, Bennet, JE, Bernotiene, G, Bi, Y, Bienek, A, Björkelund, C, Bo, S, Boehm, BO, Bonaccio, M, Bongard, V, Borchini, R, Borghs, H, Breckenkamp, J, Brenner, H, Bruno, G, Busch, MA, CabreradeLeón, A, Capuano, V, Casanueva, FF, Casas, J-P, Caserta, CA, Censi, L, Chen, F, Chen, S, Chirlaque, M-D, Cho, B, Cho, Y, Chudek, J, Claessens, F, Clarke, J, Clays, E, Cooper, C, Costanzo, S, Cottel, D, Cowell C, Crujeiras, AB, Cui, L, D'Arrigo, G, Dauchet, L, De Backer, G, De Bacquer, D, de Gaetano, G, De Henauw, S, De Smedt, D, Dennison, E, Desschamps, V, Di Castelnuovo, A, Dobson, AJ, Donfrancesco, C, Döring, A, Doua, K, Drygas, W, Du, Y, Dziankowska-Zaborszczyk, E, Eggertsen, R, Ekelund, U, Elousa, R, Eriksson, JG, Evans, A, Faeh, D, Felix-Redondo, FJ, Fernández-Bergés, D, Ferrari, M, Ferrieres, J, Finn, JD, Forslund, A-S, Forsner, M, Frontera, G, Fujita, Y, Gaciong, Z, Galvano, F, Gao, J, Garcia-de-la-Hera, M, Garnett, SP, Gaspoz, J-M, Gasul, L, Gates, L, Gianfagna, F, Gill, TK, Giovannelli, J, Goltzman, D, GonzalezGross, M, Gottrand, F, Graff-Iversen, S, Grafnetter, D, Gregor, RD, Grodzicki, T, Grosso, G, Gruden, G, Gu, D, Guallar-Castillón, P, Gudmundsson, EF, Guessous, I, Gunnlaugsdottir J, Gutzwiller, F, Hardy, R, Hata, J, Haugsgjerd, T, Hayes, AJ, He, H, He, Y, Herrala, S, Hihtaniemi, IP, Hobbs, M, Hopman, WM, Huerta, JM, Huybrechts, I, Iacoviello, L, Iannone, AG, Ikeda, N, Iwasaki, M, Jackson, R, Jamrozi, K, Janszky, I, Jarvelin, M-R, Jasienska, G, Jennings, G, Jeong, S-L, Jiang, CQ, Joffres, M, Jokelainen, JJ, Jonas, JB, Jóźwiak, J, Kajantie, EO, Kauhanen, K, Keil, U, Keinänen-Kiukaanniemi, S, Kersting, M, Khang, Y-H, Kiechl-Kohlendorfer, U, Kiechl, S, Kim, J, Kim, Y-Y, Klumbiene, J, Knoflach, M, Ko, S, Kolle, E, Korpelainen, R, Koskinen, S, Kouda, K, Kratzer, W, Kriemler, S, Krokstad, S, Kujala,UM, Kurjata, P, Lam, TH, Lanska, V, Lappas , G, Laugsand, LE, Lee, J, Lehtimäki, T, Li, Y, Lilly, C, Lin, X, Lind, L, Lissner, L, Liu, J, Lopez-Garcia, E, Lorbeer, R, Lozano, JE, Luksiene, D, Lundqvist, A, Lundqvist, R, Lytsy, P, Ma, G, Machi, S, Maggi, S, Magliano, DJ, Manzato, E, Mathiesen, EB, McLachlan, S, McLean, RM, Meirhaeghe, A, Metcalf, P, Mi, JM, Miller, JC, Moreno, LA, Morin, S, Mossakowska, M, Muiesan, ML, Mursu, J, Nakamura, H, Námešná, J, Navarrete-Muñoz, EM, Neal, WA, Nenko, I, Niiranen, T, Ning, G, Noale, M, Norie, S, Noto, Davide, O’Neill, T, O'Reilly, D, Oh, K, Olafsson, O, Paccaud, F, Pajak, A, Palmieri, L, Panza, F, Parnell, WR, Peltonen, M, Peters, A, Petersmann, A, P Pigeot, I, Pilotto, L, Piwonska, A, Pedro Plans-Rubió, P, Porta, M, Price, JF, Puder, JJ, Puhakka, SE, Radisauskas, R, Raitakari, O, Ramos, R, Redon, J, Rigo, F, Rodriguez-Perez, MdC, Romaguera, D, Ronkainen, K, Rosengren, A, Roy, JGR, Ruidavets, JB, Rutkowski, M, Salanave, B, Salmeron, D, Salomaa, V, Salonen, JT, Salvetti, M, Sans, S, Saramies, JL, Saum, K-U, Scheidt-Nave, C, Schienkiewitz, A, Schipf, S, Schmidt, CO, Schottker, B, Sebert S, Sen, A, Shaw, JE, Shibuya, K, Shin, DO, Shiri, R, Simons, J, Simons, LA, Sjostrom, M, Slowikowska-Hilczer, J, Slusarczyk, P, Solfrizzi, V, Sonestedt, E, Soumare, A, Staessen, JA, Stathopoulou, MG, Steene-Johannessen, J, Stehle, P, Stieber, J, Stöckl, D, Stokwiszewski, J, Sundström, J, Suriyawongpaisal, P, Tamosiunas, A, Tan, E, Taylor, A, Tell, G, Thijs, L, Tolonen, HK, Topór-Madry, R, Tormo, MJ, Torrent, M, Tsugane, S, Tuomainen, T-P, Tuomilehto, J, Tzourio, C, Uusitalo, HMT, Van Herck, K, Vanderschueren, D, Vanuzzo, D, Vatten, L, Vega, T, Veronesi, G, Vioque, P, Virtanen, JK, Visvikis-Siest, S, Vollenweider, P, Voutilainen, S, Vrijheid, M, Wagner, A, Wang, M-D, Wang, Q, Wang YX, Wannamethee, SG, Wei, W, Whincup, PH, Wiecek, A, Willeit, J, Willeit, P, Wojtyniak, B, Wong, A, Woodward, M, Wu, FC, JianFeng Wu, JF, Wu, SL, Xu, H, Xu, L, Yan, W, Yang, X, Ye, X, Yoshihara, A, Zambon, S, Zhao, W, NCD Risk Factor Collaboration (NCD-RisC), Jackson, R., Zhou, B., Bixby, H., Danaei, G., Di Cesare, M., Kuulasmaa, K., Hajifathalian, K., Bentham, J., Bennett, J.E., Aekplakorn, W., Cifkova, R., Dallongeville, J., DeBacquer, D., Giampaoli, S., Gudnason, V., Khang, Y.H., Laatikainen, T., Mann, J., Marques-Vidal, P., Mensah, G.A., Müller-Nurasyid, M., Ninomiya, T., Petkeviciene, J., Rodríguez-Artalejo, F., Servais, J., Söderberg, S., Stavreski, B., Wilsgaard, T., Zdrojewski, T., Zhao, D., Stevens, G.A., Savin, S., Cowan, M.J., Riley, L.M., Ezzati, M., Adams, R.J., Ahrens, W., Amouyel, P., Amuzu, A., Anderssen, S.A., Ariansen, I., Arveiler, D., Aspelund, T., Auvinen, J., Avdicová, M., Banach, M., Bandosz, P., Banegas, J.R., Barbagallo, C.M., Bata, I., Baur, L.A., Beaglehole, R., Bernotiene, G., Bi, Y., Bienek, A., Björkelund, C., Bo, S., Boehm, B.O., Bonaccio, M., Bongard, V., Borchini, R., Borghs, H., Breckenkamp, J., Brenner, H., Bruno, G., Busch, M.A., Cabrera de León, A., Capuano, V., Casanueva, F.F., Casas, J.P., Caserta, C.A., Censi, L., Chen, F., Chen, S., Chirlaque, M.D., Cho, B., Cho, Y., Chudek, J., Claessens, F., Clarke, J., Clays, E., Cooper, C., Costanzo, S., Cottel, D., Cowell, C., Crujeiras, A.B., Cui, L., D'Arrigo, G., Dauchet, L., De Backer, G., De Bacquer, D., de Gaetano, G., De Henauw, S., De Smedt, D., Dennison, E., Deschamps, V., DiCastelnuovo, A., Dobson, A.J., Donfrancesco, C., Döring, A., Drygas, W., Du, Y., Dziankowska-Zaborszczyk, E., Eggertsen, R., Ekelund, U., Elosua, R., Eriksson, J.G., Evans, A., Faeh, D., Felix-Redondo, F.J., Fernández-Bergés, D., Ferrari, M., Ferrieres, J., Finn, J.D., Forslund, A.S., Forsner, M., Frontera, G., Fujita, Y., Gaciong, Z., Galvano, F., Gao, J., Garcia-de-la-Hera, M., Garnett, S.P., Gaspoz, J.M., Gasull, M., Gates, L., Gianfagna, F., Gill, T.K., Giovannelli, J., Goltzman, D., GonzalezGross, M., Gottrand, F., Graff-Iversen, S., Grafnetter, D., Gregor, R.D., Grodzicki, T., Grosso, G., Gruden, G., Gu, D., Guallar-Castillón, P., Gudmundsson, E.F., Guessous, I., Gunnlaugsdottir, J., Gutzwiller, F., Hardy, R., Hata, J., Haugsgjerd, T., Hayes, A.J., He, J., He, Y., Herrala, S., TapaniHihtaniemi, I., Hobbs, M., Hopman, W.M., MaríaHuerta, J., Huybrechts, I., Iacoviello, L., Iannone, A.G., Ikeda, N., Iwasaki, M., Jamrozik, K., Janszky, I., Jarvelin, M.R., Jasienska, G., Jennings, G., Jeong, S.L., QiangJiang, C., Joffres, M., Jokelainen, J.J., Jonas, J.B., Jóźwiak, J., Kajantie, E.O., Kauhanen, J., Keil, U., Keinänen-Kiukaanniemi, S., Kersting, M., Kiechl-Kohlendorfer, U., Kiechl, S., Kim, J., Kim, Y.Y., Klumbiene, J., Knoflach, M., Ko, S., Kolle, E., Korpelainen, R., Koskinen, S., Kouda, K., Kratzer, W., Kriemler, S., Krokstad, S., Kujala, U.M., Kurjata, P., HingLam, T., Lanska, V., Lappas, G., Laugsand, L.E., Lee, J., Lehtimäki, T., Li, Y., Lilly, C.L., Lin, X., Lind, L., Lissner, L., Liu, J., Lopez-Garcia, E., Lorbeer, R., EugenioLozano, J., Luksiene, D., Lundqvist, A., Lundqvist, R., Lytsy, P., Ma, G., Machi, S., Maggi, S., Magliano, D.J., Manzato, E., Mathiesen, E.B., McLachlan, S., McLean, R.M., McLean, S.B., Meirhaeghe, A., Meisinger, C., Metcalf, P., Mi, J., Miller, J.C., Moreno, L.A., Morin, S., Mossakowska, M., Muiesan, M.L., Mursu, J., Nakamura, H., Námešná, J., Nauck, M., MariaNavarrete-Muñoz, E., Neal, W.A., Nenko, I., Niiranen, T.J., Ning, G., Noale, M., Norie, S., Noto, D., O'Neill, T., O'Reilly, D., Oh, K., Olafsson, Ö., MichelPaccaud, F., Pajak, A., Palmieri, L., Panza, F., Parnell, W.R., Peltonen, M., Peters, A., Petersmann, A., Pigeot, I., Pilotto, L., Piwonska, A., Plans-Rubió, P., Porta, M., Price, J.F., Puder, J.J., Puhakka, S.E., Radisauskas, R., Raitakari, O., Ramos, R., Redon, J., Rigo, F., Rodriguez-Perez, M., Romaguera, D., Ronkainen, K., Rosengren, A., Ruidavets, J.B., Rutkowski, M., Salanave, B., Salmerón, D., Salomaa, V., Salonen, J.T., Salvetti, M., Sans, S., Saramies, J.L., Saum, K.U., Scheidt-Nave, C., Schienkiewitz, A., Schipf, S., Schmidt, C.O., Schöttker, B., Sebert, S., Sen, A., Shaw, J.E., Shibuya, K., WookShin, D., Shiri, R., Simons, J., Simons, L.A., Sjöström, M., Slowikowska-Hilczer, J., Slusarczyk, P., Solfrizzi, V., Sonestedt, E., Soumare, A., Staessen, J.A., Stathopoulou, M.G., Steene-Johannessen, J., Stehle, P., Stieber, J., Stöckl, D., Stokwiszewski, J., Sundström, J., Suriyawongpaisal, P., Tamosiunas, A., JooTan, E., Taylor, A., Tell, G., Thijs, L., Tolonen, H., Topór-Madry, R., JoséTormo, M., Torrent, M., Tsugane, S., Tuomainen, T.P., Tuomilehto, J., Tzourio, C., Van Herck, K., Vanderschueren, D., Vanuzzo, D., Vatten, L., Vega, T., Veronesi, G., Vioque, J., Virtanen, J., Visvikis-Siest, S., Vollenweider, P., Voutilainen, S., Vrijheid, M., Wagner, A., Wang, M.D., Wang, Q., XingWang, Y., Wannamethee, S.G., Wei, W., Whincup, P.H., Wiecek, A., Willeit, J., Willeit, P., Wojtyniak, B., Wong, A., Woodward, M., GiwercmanWu, A., Wu, F.C., Wu, S., Xu, H., Xu, L., Yan, W., Yang, X., Ye, X., Yoshihara, A., Zambon, S., Zhao, W., Universiteit Gent = Ghent University (UGENT), Istituto Superiore di Sanità (ISS), Helmholtz Zentrum München = German Research Center for Environmental Health, Kyushu University, The Arctic University of Norway [Tromsø, Norway] (UiT), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Catania = University of Catania (Unict), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Brescia = University of Brescia (UniBs), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Medical University of Silesia, Katowice, University of Helsinki, National Institute for Health and Welfare, University of Helsinki, University of Helsinki, and University of Helsinki, Finnish Institute of Occupational Health
Subjects: Male, gupo de ascendencia continental asiática, Settore MED/09 - Medicina Interna, Total Cholesterol, Ldl Cholesterol, Hdl Cholesterol, Blood Lipids, Multi-country Study, Epidemiology, kolesteroli, humanos, Blood lipids, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, triglicéridos, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, HDL cholesterol, Medicine and Health Sciences, CARDIOVASCULAR RISK-FACTORS, Medicine, 030212 general & internal medicine, mediana edad, lípidos, Public, Environmental & Occupational Health, 2. Zero hunger, anciano, education.field_of_study, Age Factors, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, colesterol, adulto, kansainvälinen vertailu, Lipids, 3142 Public health care science, environmental and occupational health, 3. Good health, Europe, Cholesterol, Population Surveillance, LDL cholesterol, SERUM-LIPIDS, Female, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Adult, Asian Continental Ancestry Group, Canada, Total cholesterol, blood lipids, multi-country study, medicine.medical_specialty, Asia, Medicina, European Continental Ancestry Group, Population, Nursing, HDL-kolesteroli, White People, DIETARY-FAT, 03 medical and health sciences, Sex Factors, Asian People, kansanterveys, vigilancia de la población, Humans, CORONARY-HEART-DISEASE, ddc:610, LDL-kolesteroli, education, Triglycerides, METAANALYSIS, Aged, INDIVIDUAL DATA, Science & Technology, business.industry, Omvårdnad, blood lipid, Cholesterol, HDL, Ecological study, nutritional and metabolic diseases, Cholesterol, LDL, United States, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cholesterol/blood, Lipids/blood, Population Surveillance/methods, Triglycerides/blood, chemistry, WORLDWIDE TRENDS, Multi-country study, grupo de ascendencia continental europea, business, HIGH-DENSITY-LIPOPROTEIN, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography, Lipoprotein
Abstract: Artículo con numerosos autores. Sólo quedan reflejados el primero, los pertenecientes a la UAM y el colectivo, Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol., This work was supported by the Wellcome Trust (grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z). R.C. acknowledges funding from the Ministry of Health of the Czech Republic (grant number 15-27109A)
Published: 2020

40. Validation of a novel milk progesterone-based tool to monitor luteolysis in dairy cows: Timing of the alerts and robustness against missing values

Author: Nicolas Friggens, Olivier Martin, Bart De Ketelaere, Wouter Saeys, Ines Adriaens, Ben Aernouts, Department of Biosystems, MeBioS, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Modélisation Systémique Appliquée aux Ruminants (MoSAR), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT)110770FWO11ZG916N12K3916NINRA V410318NEuropean Union (EU)FP7.KBBE.2012.6311776, and Institut National de la Recherche Agronomique (INRA)-AgroParisTech
Subjects: DYNAMICS, PREDICTION, Computer science, Luteolysis, OVARIAN CYSTS, milk progesterone, Statistics, Insemination, Artificial, Progesterone, 2. Zero hunger, fertility, 0303 health sciences, Agriculture, 04 agricultural and veterinary sciences, simulation, Milk, Agriculture, Dairy & Animal Science, Food Science & Technology, Female, Life Sciences & Biomedicine, Algorithms, Farms, Luteal phase, Insemination, 03 medical and health sciences, Chart, Corpus Luteum, Robustness (computer science), [SDV.SA.STA]Life Sciences [q-bio]/Agricultural sciences/Sciences and technics of agriculture, Genetics, Animals, Lactation, REPRODUCTIVE-PERFORMANCE, Monitoring, Physiologic, 030304 developmental biology, Science & Technology, Observational error, dairy cow, 0402 animal and dairy science, PROFILES, Kalman filter, Missing data, Statistical process control, 040201 dairy & animal science, monitoring tool, MODEL, Cattle, Animal Science and Zoology, Food Science, Test data
Abstract: Automated monitoring of fertility in dairy cows using milk progesterone is based on the accurate and timely identification of luteolysis. In this way, well-adapted insemination advice can be provided to the farmer to further optimize the fertility management. To properly evaluate and compare the performance of new and existing data-processing algorithms, a test dataset of progesterone time-series that fully covers the desired variability in progesterone profiles is needed. Further, the data should be measured with a high frequency to allow rapid onset events, such as luteolysis, to be precisely determined. Collecting this type of data would require a lot of time, effort and budget. In the absence of such data, an alternative was developed using simulated progesterone profiles for multiple cows and lactations, in which the different fertility statuses were represented. To these, relevant variability in terms of cycle characteristics and measurement error was added, resulting in a large cost-efficient dataset of well-controlled but highly variable and farm-representative profiles. Besides the progesterone profiles, information on (the timing of) luteolysis was extracted from the modelling approach and used as a reference for the evaluation and comparison of the algorithms. In this study, two progesterone monitoring tools were compared: a multiprocess Kalman filter combined with a fixed threshold on the smoothed progesterone values to detect luteolysis, and a progesterone monitoring algorithm using synergistic control ‘PMASC’, which uses a mathematical model based on the luteal dynamics and a statistical control chart to detect luteolysis. The timing of the alerts and the robustness against missing values of both algorithms were investigated using two different sampling schemes: one sample per cow every eight hours versus one sample per day. The alerts for luteolysis of the PMASC algorithm were on average 20 hours earlier compared to the ones of the multiprocess Kalman filter, and their timing was less sensitive to missing values. This was shown by the fact that, when one sample per day was used, the Kalman filter gave its alerts on average 24 hours later, and the variability in timing of the alerts compared to simulated luteolysis increased with 22%. Accordingly, we postulate that implementation of the PMASC system could improve the consistency of luteolysis detection on farm and lower the analysis costs compared to the current state of the art.Interpretative SummaryValidation of luteolysis monitoring tool for dairy cows.AdriaensIn this study, the performance of two monitoring algorithms to detect luteolysis using milk progesterone measurements was validated on a simulated dataset of realistic milk progesterone profiles. The synergistic control-based algorithm, PMASC, was able to identify luteolysis almost simultaneously with its occurrence. It was found to be more robust against missing samples and less dependent on the absolute milk progesterone values compared to a multiprocess Kalman filter combined with a fixed threshold. This research showed that implementation of PMASC could improve progesterone-based fertility monitoring on farm.
Published: 2019

41. Linking macrodetritivore distribution to desiccation resistance in small forest fragments embedded in agricultural landscapes in Europe

Author: Ludmilla Martin, Martin Hermy, Astra Ooms, Willem Proesmans, Sara A. O. Cousins, Pallieter De Smedt, Jaan Liira, Lander Baeten, Marc Deconchat, Monika Wulf, Emilie Gallet-Moron, Brice Giffard, Matty P. Berg, Guillaume Decocq, Kris Verheyen, Jörg Brunet, Alicia Valdés, Dries Bonte, Martin Diekmann, Forest & Nature Lab, Universiteit Gent = Ghent University [Belgium] (UGENT), University of Amsterdam [Amsterdam] (UvA), Swedish University of Agricultural Sciences (SLU), Stockholm University, Ecologie et Dynamique des Systèmes Anthropisés - UMR CNRS 7058 (EDYSAN), Centre National de la Recherche Scientifique (CNRS)-Université de Picardie Jules Verne (UPJV), Dynamiques Forestières dans l'Espace Rural (DYNAFOR), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Bremen, Bordeaux Sciences Agro, Université de Bordeaux, Institute of Ecology and Earth Sciences [Tartu], University of Tartu, Department of Ecology, Environment and Plant Sciences, Leibniz-Zentrum für Agrarlandschaftsforschung = Leibniz Centre for Agricultural Landscape Research (ZALF), Division of Forest, Nature and Landscape, Department of Earth and Environmental Sciences [Leuven] (EES), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Animal Ecology, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), and Conservation Ecology Group
Subjects: 0106 biological sciences, DISTRIBUTION PATTERNS, [SDV]Life Sciences [q-bio], Geography, Planning and Development, GRADIENTS, 010603 evolutionary biology, 01 natural sciences, Nutrient cycling, [SHS]Humanities and Social Sciences, LITTER DECOMPOSITION, NORTHERN FRANCE, Ecosystem, SDG 2 - Zero Hunger, Woodlice, Nature and Landscape Conservation, SDG 15 - Life on Land, Ecology, Resistance (ecology), Land use, Community structure, LAND-USE INTENSITY, TERRESTRIAL ISOPODS, 04 agricultural and veterinary sciences, Forest edges, 15. Life on land, Plant litter, Landscape use intensity, Litter dwelling soil fauna, WOODLICE ISOPODA ONISCIDEA, Geography, Habitat, Millipedes, EDGE, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Landscape ecology, Desiccation, LEAF-LITTER
Abstract: International audience; Purpose Most of the agricultural landscape in Europe, and elsewhere, consists of mosaics with scattered fragments of semi-natural habitat like small forest fragments. Mutual interactions between forest fragments and agricultural areas influence ecosystem processes such as nutrient cycling, a process strongly mediated by the macrodetritivore community, which is however, poorly studied. We investigated macrodetritivore distribution patterns at local and landscape level and used a key functional trait (desiccation resistance) to gain mechanistic insights of the putative drivers. Methods Macrodetritivores were sampled in forest edges-centres of 224 European forest fragments across 14 landscapes opposing in land use intensity. We used a multilevel analysis of variance to assess the relative contribution of different spatial scales in explaining activity-density and Shannon-diversity of woodlice and millipedes, together with a model-based analysis of the multivariate activity-density data testing the effect on species composition. Secondly, we tested if desiccation resistance of macrodetritivores varied across communities at different spatial scales using linear mixed effect models. Results Forest edge-centre and landscape use intensity determined activity-density and community composition of macrodetritivores in forest fragments, while fragment characteristics like size and continuity were relatively unimportant. Forest edges and higher intensity landscapes supported higher activity-density of macrodetritivores and determined species composition. Forest edges sustained woodlouse communities dominated by more drought tolerant species. Conclusions Landscape use intensity and forest edges are main drivers in macrodetritivore distribution in forest fragments with desiccation resistance a good predictor of macrodetritivore distribution. Key functional traits can help us to predict changes in community structure in changing landscapes.
Published: 2018

42. The emergence of the grammatical paradigm of nominal determiners in French and in Romance: Comparative and diachronic perspectives

Author: Béatrice Lamiroy, Anne Carlier, Savoirs, Textes, Langage (STL) - UMR 8163 (STL), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Franitalco Université de Leuven, Unité de recherche de linguistique française, italienne et comparéeFranitalco (Franitalco), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), ANR-14-FRAL-0006,PaLaFra,Le PAssage du LAtin au FRAnçais: constitution et analyse d'un corpus numérique latino-français(2014), Sorbonne Université (SU), Équipe Histoire des usages linguistiques (STIH-HUL), Sens, Texte, Informatique, Histoire (STIH), and Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 060201 languages & linguistics, Linguistics and Language, History, Analogy, French, 06 humanities and the arts, Nous, Romance languages, 16. Peace & justice, Grammaticalization, Possessive, Romance, Language and Linguistics, language.human_language, [SHS]Humanities and Social Sciences, Noun, 0602 languages and literature, language, [SHS.LANGUE]Humanities and Social Sciences/Linguistics, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: This article is devoted to the emergence of a new paradigm in French and Romance: that of nominal determiners. Latin had no articles, and although possessives, demonstratives and indefinites could determine the noun, they could also be used as pronouns or adjectives, so that the morpho-syntactic category of nominal determiners did not exist as such. We first examine the diachronic evolution of French, where a far-reaching grammaticalization process took place. Syntagmatically, all determiners end up in the NP-initial position as the only available syntactic slot, contributing to the highly configurational NP pattern characteristic of Modern French. From a paradigmatic viewpoint, determiners no longer correspond to a syntactic function, but to a separate morpho-syntactic category. We also evaluate to what extent this evolution took place in two other Romance languages, Italian and Spanish. Through the analysis of this particular evolution, based on parallel corpora consisting of a Latin text and its translations in Old, Middle, and Modern French on the one hand, and in Spanish and Italian on the other, our study also provides evidence for more general mechanisms, analogy in particular, at work in the creation of new paradigms. Resume: Cet article est consacre a l'emergence d'un nouveau paradigme grammatical en francais et dans les langues romanes, celui de la determination nominale. Le latin n'avait pas d'articles, alors que les possessifs, les demonstratifs et les indefinis, tout en pouvant servir de determinant nominal, etaient par ailleurs utilises comme pronom ou adjectif. La determination nominale en tant que categorie morpho-syntaxique autonome etait donc inexistante. Nous examinons d'abord comment a eu lieu, au cours de l'evolution diachronique du francais, un processus important de grammaticalisation. Syntagmatiquement, tous les determinants se retrouvent dans la position initiale du NP comme seule position syntaxique disponible, ce qui contribue au caractere hautement configurationnel du constituant nominal du francais moderne. D'un point de vue paradigmatique, les determinants ne correspondent plus a une fonction syntaxique, mais a une categorie morphosyntaxique distincte. Nous evaluons ensuite dans quelle mesure cette evolution a eu lieu dans deux autres langues romanes, l'italien et l'espagnol. Notre analyse est basee sur des corpus paralleles comprenant un texte latin et ses traductions en francais medieval et moderne, d'une part, et ses traductions en espagnol et en italien, d'autre part. Elle met en evidence des mecanismes et des motivations plus generaux, notamment l'analogie, qui sont a l'œuvre dans la creation de nouveaux paradigmes.
Published: 2018

43. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

Author: Marc André, Peter Vandenberghe, Laurent Knoops, Aspasia Stamatoullas, Ioanna-Andrea Stoian, Oumedaly Reman, Eric Van Den Neste, Sarah Bailly, Olivier Casasnovas, Herve Ghesquieres, Romain Dubois, Corinne Haioun, Marie-José Claessen, Franck Morschhauser, Thomas Gastinne, Gregor Verhoef, Marie-Christine Copin, Hélène Poirel, Amine Belhabri, A. Cottereau, Cliniques Universitaires Saint-Luc [Bruxelles], CHU UCL Namur, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Henri Mondor, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Hospitals Leuven [Leuven], Erasmus University Rotterdam, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, CHU Henri Mondor [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinical Haematology, Hematology, Université de Lille, CHU Lille, CNRS, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - EA 7365, Centre hospitalier universitaire de Nantes [CHU Nantes], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen [CLCC Henri Becquerel], Université Claude Bernard Lyon 1 [UCBL], Catholic University of Leuven - Katholieke Universiteit Leuven [KU Leuven], Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T], Mouvement, Équilibre, Performance, Santé [MEPS], Université Catholique de Louvain = Catholic University of Louvain [UCL], and Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Subjects: Male, 0301 basic medicine, Ruxolitinib, Administration, Oral, Salvage therapy, Phases of clinical research, Gastroenterology, 0302 clinical medicine, hemic and lymphatic diseases, Aged, 80 and over, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Prognosis, Hodgkin Disease, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Article, Young Adult, 03 medical and health sciences, Internal medicine, Nitriles, medicine, Refractory Hodgkin Lymphoma, Humans, Adverse effect, Protein Kinase Inhibitors, Survival rate, Aged, Salvage Therapy, Hodgkin Lymphoma, business.industry, Janus Kinase 1, Janus Kinase 2, medicine.disease, Discontinuation, Pyrimidines, 030104 developmental biology, Drug Resistance, Neoplasm, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Pyrazoles, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: International audience; JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in patients with relapsed/refractory Hodgkin lymphoma. The primary objective was overall response rate according to the International Harmonization Project 2007 criteria. Thirty-three patients with advanced disease (median number of prior lines of treatment: 5; refractory: 82%) were included; nine (27.3%) received at least six cycles of ruxolitinib and six (18.2%) received more than six cycles. The overall response rate after six cycles was 9.4% (3/32 patients). All three responders had partial responses; another 11 patients had transient stable disease. Best overall response rate was 18.8% (6/32 patients). Rapid alleviation of B-symptoms was common. The median duration of response was 7.7 months, median progression-free survival 3.5 months (95% CI: 1.9-4.6), and the median overall survival 27.1 months (95% CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%). One event led to treatment discontinuation, while 87.5% of patients recovered without sequelae. Twenty-five adverse events were grade 3 or higher. These events were mostly anemia (n=11), all considered related to ruxolitinib. Other main causes of grade 3 or higher adverse events included lymphopenia and infections. Of note, no cases of grade 4 neutropenia or thrombocytopenia were observed. Ruxolitinib shows signs of activity, albeit short-lived, beyond a simple anti-inflammatory effect. Its limited toxicity suggests that it has the potential to be combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005.
Published: 2018

44. Effect of operational parameters on the performance of a magnetic responsive biocatalytic membrane reactor

Author: Pierre Aimar, Lidietta Giorno, Thierry Verbiest, Abaynesh Yihdego Gebreyohannes, Ivo F.J. Vankelecom, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Università della Calabria [Arcavacata di Rende] (Unical), Laboratoire de génie chimique [ancien site de Basso-Cambo] (LGC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique - CNRS (FRANCE), Consiglio Nazionale delle Ricerche - CNR (ITALY), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Università della Calabria (ITALY), Katholieke Universiteit Leuven - KU LEUVEN (BELGIUM), Laboratoire de Génie Chimique - LGC (Toulouse, France), and Institut National Polytechnique de Toulouse - INPT (FRANCE)
Subjects: Membrane fouling, Materials science, Immobilized enzyme, Continuous operation, General Chemical Engineering, Magnetic nanoparticle, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Industrial and Manufacturing Engineering, [CHIM.GENI]Chemical Sciences/Chemical engineering, Génie chimique, Environmental Chemistry, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Génie des procédés, Nanocomposite, Chromatography, Fouling, Membrane reactor, General Chemistry, Permeation, 021001 nanoscience & nanotechnology, Stimuli-responsive membrane, 0104 chemical sciences, Volumetric flow rate, Membrane, Chemical engineering, Biocatalysis, Packed bed reactor, 0210 nano-technology
Abstract: International audience; In this work, the performance of an innovative magnetic responsive biocatalytic membrane reactor (BMRSP) has been investigated under various operational parameters. In particular, feed concentrations, flow rates across the bed, temperature and amount of biocatalytic bead were varied to probe the flow-dependent transport and kinetic properties of the reaction and the subsequent hydrolytic performance of the BMRSP. The rate of fouling for the BMRSP was always lower than a corresponding control system. For a given enzymatic concentration, a constant foulant hydrolyzing capacity is identified. At 3 g/m2 pectinase containing bionanocomposites, the BMRSP hydrolytic efficiency was 1.5 g/m2 h. This efficiency was further increased by increasing the amount of bionanocomposites per membrane area. This further allowed the BMRSP to hydrolyze higher loads of foulants while keeping a low if not zero increase in TMP over time at constant flux. Identification of an optimal operating condition laid the platform for continuous operation of the BMRSP over 200 h, without visible transmembrane pressure drift while maintaining constant flux. Product assay in the permeate gave constant value in the entire duration, i.e., no enzymatic activity decay owing to stable enzyme immobilization and no leakage through the pores of the membrane owing to the synergistic magnetic interaction between the magnetic membrane and magnetic bionanocomposites. The obtained stability over a broad range of operational parameters and sustainable performance over long period gives a high prospect to the newly developed BMRSP to be utilized in continuous biocatalysis and separation, thereby significantly improved process efficiency.
Published: 2017

45. Desiccation resistance determines distribution of woodlice along forest edge-to-interior gradients

Author: Martin Diekmann, Dries Bonte, Martin Hermy, Sara A. O. Cousins, Pieter De Frenne, Matty P. Berg, Pallieter De Smedt, Lander Baeten, Emilie Gallet-Moron, Guillaume Decocq, Kris Verheyen, Brice Giffard, Jörg Brunet, Conservation Ecology Group, Forest & Nature Lab, Universiteit Gent = Ghent University [Belgium] (UGENT), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Université de Picardie Jules Verne (UPJV), Southern Swedish Forest Research Centre, Swedish University of Agricultural Sciences (SLU), Stockholm University, University of Bremen, Dynamiques Forestières dans l'Espace Rural (DYNAFOR), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Bordeaux Sciences Agro, Université de Bordeaux, Division of Forest, Nature and Landscape, Department of Earth and Environmental Sciences [Leuven] (EES), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Animal Ecology, and VU University Amsterdam
Subjects: 0106 biological sciences, Nutrient cycle, Response trait, DISTRIBUTION PATTERNS, Soil Science, 010603 evolutionary biology, 01 natural sciences, Microbiology, LITTER DECOMPOSITION, Isopoda, Abundance (ecology), MACROARTHROPODS, Ecosystem, Small forest fragments, SDG 15 - Life on Land, Abiotic component, biology, Resistance (ecology), Ecology, Edge effects, Detritivore, TERRESTRIAL ISOPODS, 04 agricultural and veterinary sciences, 15. Life on land, Drought tolerance, biology.organism_classification, Insect Science, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Environmental science, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, FRAGMENTATION, MILLIPEDES, Desiccation, TRAITS
Abstract: International audience; Forest edges show strong abiotic and biotic gradients potentially altering community composition and ecosystem processes such as nutrient cycling. While abiotic gradients are well studied, short-scale biotic gradients, like detritivore species composition and their associated trait distribution remains a poorly explored research-field. We sampled woodlice in 160 forest patches across Europe at varying distances from the forest edge and discovered that species desiccation resistance determines distribution along forest edge-to-interior gradients. Forest edges are warmer and dryer compared to interiors and favour drought-tolerant species, while abundance and activity of drought-sensitive species is reduced at the edge. Key ecological factors for litter-dwelling detritivores (i.e. humidity) act as environmental filter, because of species-specific differences in desiccation resistance. Future research should focus on quantifying the consequences of a changing detritivore community and their associated functional traits for nutrient cycling.
Published: 2018

46. Global distribution of earthworm diversity

Author: André L.C. Franco, Michiel Rutgers, Miguel Á. Rodríguez, Thomas W. Crowther, Helen Phillips, Tunsisa T. Hurisso, Olaf Schmidt, Matthew W. Warren, Shishir Paudel, Michael B. Wironen, Mónica Gutiérrez López, Basil V. Iannone, Aidan M. Keith, Amy Choi, Esperanza Huerta Lwanga, Boris Schröder, Olga Ferlian, Jaswinder Singh, Javier Rodeiro-Iglesias, Martin Holmstrup, Geoff H. Baker, Yahya Kooch, Rosa Fernández, Konstantin B. Gongalsky, Lindsey Norgrove, Eric Blanchart, Madhav P. Thakur, Felicity Crotty, Steven J. Vanek, Thomas Bolger, Jan Hendrik Moos, Guillaume Xavier Rousseau, Marie Luise Carolina Bartz, Iñigo Virto, Michael Steinwandter, Kelly S. Ramirez, Veikko Huhta, Ulrich Brose, Michel Loreau, Davorka K. Hackenberger, David J. Russell, Loes van Schaik, Salvador Rebollo, Jonatan Klaminder, Gerardo Moreno, Benjamin Schwarz, Julia Seeber, Yvan Capowiez, David A. Wardle, Bernd Blossey, Franciska T. de Vries, Christoph Emmerling, Robert L. Bradley, Courtland Kelly, Liliana B. Falco, Alexander M. Roth, Michael J. Gundale, Radim Matula, Andrea Dávalos, Lorenzo Pérez-Camacho, Johan Neirynck, Monika Joschko, Marta Novo, Dolores Trigo, Jérôme Mathieu, Adrian A. Wackett, Anne W. de Valença, Elizabeth M. Bach, Daniel R. Lammel, Devin Routh, Madalina Iordache, Luis M. Hernández, Johan Pansu, Juan B. Jesús Lidón, Alejandro Morón-Ríos, Maxim Shashkov, Ehsan Sayad, Martine Fugère, Nobuhiro Kaneko, Mark E. Caulfield, Klaus Birkhofer, Wim H. van der Putten, Iurii M. Lebedev, Alberto Orgiazzi, Miwa Arai, H. Lalthanzara, Raphaël Marichal, Andrew R. Holdsworth, Steven J. Fonte, Maria J. I. Briones, Raúl Piñeiro, Jean-François Ponge, Nick van Eekeren, Takuo Hishi, Julia Krebs, Joanne M. Bennett, George G. Brown, Birgitta König-Ries, Carlos Fragoso, Victoria Nuzzo, Anna Rożen, Scott R. Loss, Bart Muys, Bryant C. Scharenbroch, Michael Schirrmann, Radoslava Kanianska, Irina V. Zenkova, Maria Kernecker, Abegail T Fusilero, Sandy M. Smith, Shaieste Gholami, Robin Beauséjour, Mac A. Callaham, Nathaniel H. Wehr, Yiqing Li, Kristine N. Hopfensperger, Mujeeb Rahman P, Andrés Esteban Duhour, Erin K. Cameron, Diana H. Wall, Muhammad Rashid, José Antonio Talavera, Matthias C. Rillig, Armand W. Koné, Johan van den Hoogen, Darío J. Díaz Cosín, Anahí Domínguez, Thibaud Decaëns, Fredrick O. Ayuke, Carlos A. Guerra, Guénola Pérès, Volkmar Wolters, Jiro Tsukamoto, Nico Eisenhauer, José Camilo Bedano, Weixin Zhang, Noa Kekuewa Lincoln, Visa Nuutinen, Joann K. Whalen, Christian Mulder, Sanna T. Kukkonen, German Centre for Integrative Biodiversity Research (iDiv), Universidade Positivo, Departamento de Ecología y Biología Animal, Universidad de Vigo, Crowther Lab, Institute of Integrative Biology, ETH Zürich, A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences [Moscow] (RAS), JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC), Department of Biology [Fort Collins], Colorado State University [Fort Collins] (CSU), German Centre for Integrative Biodiversity Research, Étude et compréhension de la biodiversité (ECODIV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Friedrich-Schiller-Universität Jena, Station d'écologie théorique et expérimentale (SETE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut d'écologie et des sciences de l'environnement de Paris (IEES), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA), Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Berlin-Brandenburg Institute of Advanced Biodiversity Research (BBIB), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut de recherche pour le développement [IRD] : UMR210, School of Biology and Environmental Science, University College Dublin [Dublin] (UCD), Unité de recherche Plantes et Systèmes de Culture Horticoles (PSH), Institut National de la Recherche Agronomique (INRA), Centro International de Agricultura Tropical, Red de Biodiversidad y Sistemática, Instituto de Ecología, Department of Terrestrial Ecology, Fluides, automatique, systèmes thermiques (FAST), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Biogéochimie et écologie des milieux continentaux (Bioemco), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Paris (ENS Paris), Universidad de Extremadura (UEX), Division of Forest, Nature and Landscape, Department of Earth and Environmental Sciences [Leuven] (EES), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire d'Ecologie Alpine (LECA), Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Sol Agro et hydrosystème Spatialisation (SAS), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), University of Vigo [ Pontevedra], Centre d'Ecologie et des Sciences de la COnservation (CESCO), Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center of Excellence in Environmental Studies, King Abdulaziz University, Dept Ciencias Vida, Universidad de Alcalá - University of Alcalá (UAH), Faculty of Business Administration and Economics, DS&OR-Lab, University of Paderborn, Laboratoire d'oncogénétique moléculaire, Mountain Agriculture Research Unit, University of Innsbruck, Independent, Universidad Pública de Navarra [Espagne] (UPNA), McGill University, Department of Animal Ecology and Systematics, Justus-Liebig-Universität Gießen (JLU), Jiangsu Academy of Agricultural Sciences, Université de Leipzig, Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Leipzig University, Martin-Luther-Universität Halle Wittenberg (MLU), Universidade de Vigo, Embrapa Forestry, Brazilian Agricultural Research Corporation (Embrapa), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), M.V. Lomonosov Moscow State University, Department of Biometry and Environmental System Analysis, Albert-Ludwigs-Universität Freiburg, Institute of Biodiversity, Friedrich Schiller University Jena, Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institute of Computer Science, Friedrich Schiller University Jena, Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institut d'écologie et des sciences de l'environnement de Paris (iEES), Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Catania = University of Catania (Unict), Department of Terrestrial Ecology [Wageningen], Netherlands Institute of Ecology (NIOO-KNAW), Laboratory of Nematology, Department of Plant Sciences, Wageningen University & Research, Freie Universität Berlin, Senckenberg Museum of Natural History Görlitz, Senckenberg – Leibniz Institution for Biodiversity and Earth System Research - Senckenberg Gesellschaft für Naturforschung, Leibniz Association-Leibniz Association, Global Soil Biodiversity Initiative and School of Global Environmental Sustainability, Colorado State University, Asian School of the Environment (ASE), Nanyang Technological University [Singapour], Institute for Agro-Environmental Sciences, National Agriculture and Food Research Organization, Department of Land Resource Management and Agricultural technology (LARMAT), College of 80 Agriculture and Veterinary Sciences, University of Nairobi (LARMAT), CSIRO Health & Biosecurity, Département de biologie [Sherbrooke] (UdeS), Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Geology Department, FCEFQyN, ICBIA-CONICET (National Scientific and Technical Research Council), National University of Río Cuarto, Department of Ecology, Brandenburg University of Technology, Ecologie fonctionnelle et biogéochimie des sols et des agro-écosystèmes (UMR Eco&Sols), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Department of Natural Resources, Cornell University, Cornell University [New York], UCD Earth Institute, University College Dublin, USDA Forest Service, Southern Research Station, Environnement Méditerranéen et Modélisation des Agro-Hydrosystèmes (EMMAH), Institut National de la Recherche Agronomique (INRA)-Avignon Université (AU), Farming Systems Ecology, Wageningen University and Research, Faculty of Forestry, University of Toronto, Institute of Biological, Environmental & Rural Sciences, Aberystwyth University, Department of Biological Sciences, SUNY Cortland, Department of Biodiversity, Ecology and Evolution [Madrid], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Laboratorio de Ecología, Instituto de Ecología y Desarrollo Sustentable, Universidad Nacional de Luján, Louis Bolk Institute (LBI), Department of Soil Science, Faculty of Regional & Environmental Sciences, University of Trier, Ciencias Básicas, Instituto de Ecología y Desarrollo Sustentable -INEDES, Universidad Nacional de Lujan, Institut de Biologia Evolutiva [Barcelona] (IBE / UPF - CSIC), Universitat Pompeu Fabra [Barcelona] (UPF), Department of Soil and Crop Sciences, Colorado State University, Biodiversity and Systematic Network, Instituto de Ecología A.C., Department of Biological Science and Environmental Studies, University of the Philippines - Mindanao, Natural Resources Department, Razi University, Department of Forest Ecology and Management, Swedish University of Agricultural Sciences (SLU), Department of Biology, J. J. Strossmayer University of Osijek, Agricultural Engineering, Postgraduate Program in Agroecology, Maranhão State University, Faculty of Agriculture, Kyushu University, Minnesota Pollution Control Agency, Department of Bioscience, Aarhus University, Biological Sciences, Northern Kentucky University, Agricultura Sociedad y Ambiente, El Colegio de la Frontera Sur, Soil Physics and Land Management degradation, Wageningen University & Research, Wageningen University, Department of Biological and Environmental Science [Jyväskylä Univ] (JYU), University of Jyväskylä (JYU), College of Agriculture, Environmental and Human Sciences, Lincoln University of Missouri, School of Forest Resources and Conservation [Gainesville] (UF|IFAS|FFGS), Institute of Food and Agricultural Sciences [Gainesville] (UF|IFAS), University of Florida [Gainesville] (UF)-University of Florida [Gainesville] (UF), Sustainable Development and Environment Engineering, Banat's University of Agricultural Sciences and Veterinary Medicine 'King Michael the 1st of Romania', Experimental Infrastructure Platform, Leibniz Centre for Agricultural Landscape Research (ZALF), Faculty of Food and Agricultural Sciences, Fukushima University, Matej Bel University (UMB), Centre for Ecology and Hydrology [Lancaster] (CEH), Natural Environment Research Council (NERC), Land Use and Governance, Leibniz Centre for Agricultural Landscape Research (ZALF), Climate Impacts Research Centre (CIRC), Umeå University, UR Gestion Durable des Sols, UFR Sciences de la Nature, Université Nangui Abrogoua, Tarbiat Modares University [Tehran], Natural Resources Institute Finland (LUKE), Department of Zoology, Pachhunga University College, Soil Science, ESALQ-USP, Universidade de São Paulo, College of Agriculture, Forestry and Natural Resource Management, University of Hawaii at Hilo, Tropical Plant and Soil Sciences, College of Tropical Agriculture and Human Resources, University of Hawai‘i at Mānoa, Department of Natural Resource Ecology and Management, Oklahoma State University, Performance des systèmes de culture des plantes pérennes (UPR Système de pérennes), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Department of Forest Ecology, Faculty of Forestry and Wood Sciences, Czech University of Life Sciences Prague (CZU), Department of Soil and Environment, Forest Research Institute of Baden-Wuerttemberg, Thuenen-Institute of Organic Farming, Forestry School - INDEHESA, University of Extremadura, Conservación de la Biodiversidad, El Colegio de la Frontera Sur, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Research Institute for Nature and Forest, Research Institute for Nature and Forest (INBO), School of Agricultural, Forest and Food Sciences, Bern University of Applied Sciences (BFH), Natural Area Consultants, Department of Zoology, Pocker Sahib Memorial Orphanage College, CSIRO Ocean & Atmosphere, CSIRO, Adaptation et diversité en milieu marin (AD2M), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ecology and Forest Restoration Group, Department of Life Sciences, University of Alcalá, Computing, ESEI, Vigo, Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre of Excellence in Environmental Studies, King Abdulaziz University, Environmental Sciences, COMSATS University, Life Sciences, Sciences Faculty, University of Alcalá, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Friends of the Mississippi River, Postgraduate Program in Biodiversity and Conservation, Federal University of Maranhão, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institute of Ecology, Technical University of Berlin, College of Natural Resources, University of Wisconsin, Engineering for Crop Production, Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), UCD School of Agriculture and Food Science, University College Dublin, Landscape Ecology and Environmental Systems Analysis, Institute of Geoecology, Technische Universität Braunschweig, Universität Innsbruck [Innsbruck], Institute for Alpine Environment, Eurac Research, Laboratory of Ecosystem Modelling, Institute of Physicochemical and Biological Problems in Soil Sciences, Russian Academy of Science, Laboratory of Computational Ecology, Institute of Mathematical Problems of Biology RAS – the Branch of Keldysh Institute of Applied Mathematics of Russian Academy of Sciences, Post Graduate Department of Zoology, Khalsa College Amritsar, John H. Daniels Faculty of Architecture, Landscape and Design, University of Toronto, Universidad de La Laguna [Tenerife - SP] (ULL), Faculty of Agriculture, Kochi University, Food & Agriculture, WWF-Netherlands, Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Soil, Water and Climate, University of Minnesota, Earth Innovation Institute, Department of Natural Resources & Environmental Management, University of Hawai'i at Mānoa, Natural Resource Sciences, McGill University, McGill University = Université McGill [Montréal, Canada], The Nature Conservancy, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Laboratory of Terrestrial Ecosystems, Kola Science Centre, Institute of the North Industrial Ecology Problems, Key Laboratory of Geospatial Technology for the Middle and Lower Yellow River Regions (Henan University), Ministry of Education, College of Environment and Planning, Henan University, Department of Environmental Science, Saint Mary’s University, Faculty of Biological and Environmental Sciences [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, ANR-11-IDEX-0002,UNITI,Université Fédérale de Toulouse(2011), Institute of Biology, Leipzig University, Institute of Biology, Martin Luther University Halle-Wittenberg, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Department of Biological, Geological and Environmental Sciences, University of Catania, Institute of Biology, Freie Universität Berlin, Senckenberg Museum for Natural History Görlitz, Department of Soil Zoology, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Faculty of Natural Resources & Marine Sciences, Tarbiat Modares University, Production Systems, Horticulture Technologies, Natural Resources Institute Finland, Soil Ecosystems, Natural Resources Institute Finland (Luke), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Departamento de Informática, Escuela Superior de Ingeniería Informática, Universidad de Vigo, Institute of Environmental Sciences, Jagiellonian University, Department of Ecology, University of Innsbruck, Department of Animal Biology (Zoology area), Science Faculty, University of La Laguna, Dpto. Ciencias, IS-FOOD, Universidad Pública de Navarra, Department of Animal Ecology, Justus Liebig University, University of Helsinki, German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Department of Biology, Colorado State University, Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Lomonosov Moscow State University (MSU), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Wageningen University and Research [Wageningen] (WUR), National Agriculture and Food Research Organization (NARO), University of Nairobi (UoN), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), National University of Río Cuarto = Universidad Nacional de Río Cuarto (UNRC), Brandenburg University of Technology [Cottbus – Senftenberg] (BTU), Department of Natural Resources & The Environment [CALS], College of Agriculture and Life Sciences [Cornell University] (CALS), Cornell University [New York]-Cornell University [New York], School of Biology and Environmental Sciences (SBES), USDA Forest Service, University of Toronto, Aberystwyth University, Universidad Nacional de Luján [Buenos Aires], Trier University of Applied Sciences, Razi University of Kermanshah, Josip Juraj Strossmayer University of Osijek, Universidade Estadual do Maranhão = State University of Maranhão (UEMA), Kyushu University, Aarhus University [Aarhus], Northern Kentucky University, Adaptation et diversité en milieu marin (ADMM), Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), Ecosystem and Landscape Dynamics (IBED, FNWI), Deutsche Forschungsgemeinschaft - German Research Foundation (DFG), Martin-Luther-University Halle-Wittenberg, Joint Research Centre, European Commission, Department of Biology, University of Minho [Braga], University of Amsterdam [Amsterdam] (UvA), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris), Institut National de la Recherche Agronomique (INRA)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Royal Netherlands Academy of Arts and Sciences (KNAW), Laboratory of Nematology, Department of Plant Sciences, Free University of Berlin (FU), Senckenberg Research Institute, European Project: 227161,EC:FP7:KBBE,FP7-KBBE-2008-2B,BIOBIO(2009), Biometry and Environmental System Analysis, University of Freiburg, Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Paul-Valéry - Montpellier 3 (UM3), Theoretical and Experimental Ecology Station, Centre National de la Recherche Scientifique (CNRS), Asian School of the Environment, Nanyang Technological University, Département de Biologie, Université de Sherbrooke, Sherbrooke, QC, Canada, Université de Sherbrooke, Institut National de la Recherche Agronomique (INRA)-Institut de Recherche pour le Développement (IRD)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Cornell University, UMR 1114 'EMMAH', INRA, Complutense University of Madrid (UCM), Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Forest Ecology and Management, Swedish University of Agricultural Sciences, Department of Biological and Environmental Science, University of Jyväskylä, School of Forest Resources and Conservation, University of Florida, Department of Environmental Management, Faculty of Natural Sciences, Matej Bel University, Department of Ecology and Environmental Science, Climate Impacts Research Centre, Umeå University, A.N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Performance des systèmes de culture des plantes pérennes (Cirad-Persyst-UPR 34 Système de pérennes), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Department of Forest Ecology, Faculty of Forestry and Wood Sciences, Czech University of Life Sciences Prague, Department of Earth & Environmental Sciences, KU Leuven, School of Agricultural, Forest and Food Sciences, Bern University of Applied Sciences, UMR7144 Adaptation et Diversité en Milieu Marin, Station Biologique de Roscoff, CNRS-Sorbonne Universite, AGROCAMPUS OUEST-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Department of Forest Resources, University of Minnesota, Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), European Research Council, Academy of Finland, Natural Sciences and Engineering Research Council of Canada, Russian Foundation for Basic Research, Slovak Research and Development Agency, Wageningen University and Research Centre, International Atomic Energy Agency, Fundação de Amparo à Pesquisa do Estado de São Paulo, Royal Canadian Geographical Society, Irish Government, University of Hawaii, U.S. Navy, Department of Science and Technology (India), Department of Defense (US), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Ministry of Education, Youth and Sports (Czech Republic), Agence Nationale de la Recherche (France), Austrian Science Fund, Welsh Government, Science Foundation Ireland, University of Kentucky, Higher Education Commission (Pakistan), Universidad Complutense de Madrid, Grains Research and Development Corporation (Australia), Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Ministère de l'Europe et des Affaires étrangères (France), University of Minho, Università degli Studi di Catania (UniCT), Terrestrial Ecology (TE), Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0106 biological sciences, LITTER, Earth, Planet, Climate, Biologie du sol, Biodiversity, Facteur climatique, 01 natural sciences, Ver de terre, Ecosystem services, purl.org/becyt/ford/1 [https], Soil, Abundance (ecology), FORESTS, 11. Sustainability, DRIVERS, Biomass, 2. Zero hunger, 0303 health sciences, Biomass (ecology), Multidisciplinary, biology, Ecology, Earth, 04 agricultural and veterinary sciences, POPULATION-DENSITY, earthworm, distribution, diversity, pattern, PE&RC, MINHOCAS, Habitat, Plant Production Systems, international, L20 - Écologie animale, Biodiversité, Écosystème, Zone tropicale, Soil biology, Biocénose, Invertebrados, [SDV.SA.SDS]Life Sciences [q-bio]/Agricultural sciences/Soil study, Models, Biological, 010603 evolutionary biology, Ecology and Environment, Zone tempérée, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Life Science, Animals, Ecosystem, PLANT, Oligochaeta, purl.org/becyt/ford/1.6 [https], 030304 developmental biology, Earthworm, Tropics, P34 - Biologie du sol, Species diversity, SHIFTS, Farm Systems Ecology Group, Bodemfysica en Landbeheer, 15. Life on land, Ecología, biology.organism_classification, Soil Physics and Land Management, SOIL, Agriculture and Soil Science, 13. Climate action, Plantaardige Productiesystemen, 040103 agronomy & agriculture, PATTERNS, Linear Models, 0401 agriculture, forestry, and fisheries, BIODIVERSITY, Species richness, Planet, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, COMMUNITIES, Zoology, Animal Distribution, Models Biological
Abstract: Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide., 677232 to N.E.). K.S.R. and W.H.v.d.P. were supported by ERC-ADV grant 323020 to W.H.v.d.P. Also supported by iDiv (DFG FZT118) Flexpool proposal 34600850 (C.A.G. and N.E.); the Academy of Finland (285882) and the Natural Sciences and Engineering Research Council of Canada (postdoctoral fellowship and RGPIN-2019-05758) (E.K.C.); DOB Ecology (T.W.C., J.v.d.H., and D.R.); ERC-AdG 694368 (M.R.); and the TULIP Laboratory of Excellence (ANR-10-LABX-41) (M.L.). In addition, data collection was funded by the Russian Foundation for Basic Research (12-04-01538-a, 12-04-01734-a, 14-44-03666-r_center_a, 15-29-02724-ofi_m, 16-04-01878-a 19-05-00245); Tarbiat Modares University; Aurora Organic Dairy; UGC(NERO) (F. 1-6/Acctt./NERO/2007-08/1485); Natural Sciences and Engineering Research Council (RGPIN-2017-05391); Slovak Research and Development Agency (APVV-0098-12); Science for Global Development through Wageningen University; Norman Borlaug LEAP Programme and International Atomic Energy Agency (IAEA); São Paulo Research Foundation - FAPESP (12/22510-8); Oklahoma Agricultural Experiment Station; INIA - Spanish Agency (SUM 2006-00012-00-0); Royal Canadian Geographical Society; Environmental Protection Agency (Ireland) (2005-S-LS-8); University of Hawai‘i at Mānoa (HAW01127H; HAW01123M); European Union FP7 (FunDivEurope, 265171); U.S. Department of the Navy, Commander Pacific Fleet (W9126G-13-2-0047); Science and Engineering Research Board (SB/SO/AS-030/2013) Department of Science and Technology, New Delhi, India; Strategic Environmental Research and Development Program (SERDP) of the U.S. Department of Defense (RC-1542); Maranhão State Research Foundation (FAPEMA); Coordination for the Improvement of Higher Education Personnel (CAPES); Ministry of Education, Youth and Sports of the Czech Republic (LTT17033); Colorado Wheat Research Foundation; Zone Atelier Alpes, French National Research Agency (ANR-11-BSV7-020-01, ANR-09-STRA-02-01, ANR 06 BIODIV 009-01); Austrian Science Fund (P16027, T441); Landwirtschaftliche Rentenbank Frankfurt am Main; Welsh Government and the European Agricultural Fund for Rural Development (Project Ref. A AAB 62 03 qA731606); SÉPAQ; Ministry of Agriculture and Forestry of Finland; Science Foundation Ireland (EEB0061); University of Toronto (Faculty of Forestry); National Science and Engineering Research Council of Canada; Haliburton Forest and Wildlife Reserve; NKU College of Arts and Sciences Grant; Österreichische Forschungsförderungsgesellschaft (837393 and 837426); Mountain Agriculture Research Unit of the University of Innsbruck; Higher Education Commission of Pakistan; Kerala Forest Research Institute, Peechi, Kerala; UNEP/GEF/TSBF-CIAT Project on Conservation and Sustainable Management of Belowground Biodiversity; Ministry of Agriculture and Forestry of Finland; Complutense University of Madrid/European Union FP7 project BioBio (FPU UCM 613520); GRDC; AWI; LWRRDC; DRDC; CONICET (National Scientific and Technical Research Council) and FONCyT (National Agency of Scientific and Technological Promotion) (PICT, PAE, PIP), Universidad Nacional de Luján y FONCyT [PICT 2293 (2006)], Fonds de recherche sur la nature et les technologies du Québec (131894), Deutsche Forschungsgemeinschaft [SCHR1000/3-1, SCHR1000/6-1, 6-2 (FOR 1598), WO 670/7-1, WO 670/7-2, and SCHA 1719/1-2], CONACYT (FONDOS MIXTOS TABASCO/PROYECTO11316); NSF (DGE-0549245, DGE-0549245, DEB-BE-0909452, NSF1241932); Institute for Environmental Science and Policy at the University of Illinois at Chicago; Dean’s Scholar Program at UIC; Garden Club of America Zone VI Fellowship in Urban Forestry from the Casey Tree Endowment Fund; J. E. Weaver Competitive Grant from the Nebraska Chapter of The Nature Conservancy; the College of Liberal Arts and Sciences at DePaul University; Elmore Hadley Award for Research in Ecology and Evolution from the UIC Dept. of Biological Sciences; Spanish CICYT (AMB96-1161; REN2000-0783/GLO; REN2003-05553/GLO; REN2003-03989/GLO; CGL2007-60661/BOS); Yokohama National University; MEXT KAKENHI (25220104); Japan Society for the Promotion of Science KAKENHI (25281053, 17KT0074, 25252026); ADEME (0775C0035); Ministry of Science, Innovation and Universities of Spain (CGL2017-86926-P); Syngenta Philippines; UPSTREAM; LTSER (Val Mazia/Matschertal); Marie Sklodowska Curie Postdoctoral Fellowship (747607); National Science and Technology Base Resource Survey Project of China (2018FY100306); McKnight Foundation (14-168); Program of Fundamental Researches of Presidium of Russian Academy of Sciences (AAAA-A18-118021490070-5); Brazilian National Council of Research CNPq; and French Ministry of Foreign and European Affairs. Author contributions: H.R.P.P. led the analysis, data curation, and writing of the original manuscript draft. C.A.G. assisted in analyses and writing of the original manuscript draft. E.K.C. and N.E. revised subsequent manuscript drafts. J.v.d.H., D.R., and T.W.C. provided additional analyses. E.K.C., N.E., and M.P.T. acquired funding for the project. J.K., K.B.G., B.S., M.L.C.B., M.J.I.B., and G.B. contributed to data curation. H.R.P.P., C.A.G., M.L.C.B., M.J.I.B., G.B., O.F., A.O., E.M.B., J.B., U.B., T.D., F.T.d.V., B.K.-R., M.L., J.M., C.M., W.H.v.d.P., K.S.R., M.C.R., D.R., M.R., M.P.T., D.H.W., D.A.W., E.K.C., and N.E. contributed to the project conceptualization. All authors reviewed and edited the final draft manuscript. The majority of the authors provided data for the analyses. Competing interests: The authors declare no competing interests. Data and materials availability: Data and analysis code are available on the iDiv Data repository (DOI: 10.25829/idiv.1804-5-2593) and GitHub (https://github.com/helenphillips/GlobalEWDiversity; DOI: 10.5281/zenodo.3386456).
Published: 2019

47. Sensitive bioluminescence imaging of fungal dissemination to the brain in mouse models of cryptococcosis

Author: Matthias Brock, Liesbeth Vanherp, Amy Hillen, Guilhem Janbon, Katrien Lagrou, Alexandra Ristani, Jennifer Poelmans, Uwe Himmelreich, Greetje Vande Velde, Biomedical MRI [Leuven], Department of Imaging and Pathology [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), core facility Molecular Small Animal Imaging Center (Leuven) (MoSAIC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratory of Clinical Bacteriology and Mycology [Leuven], Department of Microbiology, Immunology and Transplantation [Leuven], Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris], School of Life Sciences, University of Nottingham, UK (UON), This work was funded by the European Commission ERA-NET project ‘CryptoView’ (third call of the FP7 program Infect-ERA), the Research Foundation-Flanders (FWO, Fonds Wetenschappelijk Onderzoek, 1506114N) and KU Leuven [PF 10/017 (IMIR), CREA/14/015]. L.V. is a PhD fellow strategic basic research at the FWO (151313). J.P. received a PhD grant for strategic basic research from the Agency for Innovation by Science and Technology (IWT, 141230). G.V.V. received a postdoctoral fellowship from the FWO (12N7615N)., The authors thank Kristof Govaerts for his assistance with the MRI quantification, Dr Lore Pollaris for guidance with the endotracheal model and all partners involved in the ERA-NET project ‘CryptoView’ for the fruitful discussions., European Project: 321529,EC:FP7:HEALTH,FP7-ERANET-2012-RTD,INFECT-ERA(2013), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Fungal infection, MESH: Trachea / diagnostic imaging, Pathology, Light, MESH: Trachea / pathology, Cryptococcus, Medicine (miscellaneous), lcsh:Medicine, Disease, MESH: X-Ray Microtomography, MESH: Cryptococcosis / diagnostic imaging, Imaging, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), Non-invasive imaging, MESH: Brain / microbiology, MESH: Trachea / microbiology, MESH: Animals, MESH: Administration, Intranasal, Pathogen, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Blood-brain barrier, Mice, Inbred BALB C, medicine.diagnostic_test, biology, Brain, Cryptococcosis, Magnetic Resonance Imaging, 3. Good health, Trachea, medicine.anatomical_structure, Disease Progression, Female, MESH: Disease Progression, Bioluminescence, lcsh:RB1-214, medicine.medical_specialty, Neuroscience (miscellaneous), MESH: Mice, Inbred BALB C, Blood–brain barrier, General Biochemistry, Genetics and Molecular Biology, Mouse model, 03 medical and health sciences, medicine, lcsh:Pathology, Bioluminescence imaging, Animals, Resource Article, MESH: Brain / diagnostic imaging, Administration, Intranasal, Cryptococcus neoformans, lcsh:R, Magnetic resonance imaging, X-Ray Microtomography, biology.organism_classification, medicine.disease, MESH: Light, MESH: Luminescent Measurements, Disease Models, Animal, 030104 developmental biology, Luminescent Measurements, MESH: Brain / pathology, MESH: Cryptococcosis / pathology, Pulmonary disease, MESH: Disease Models, Animal, MESH: Female, 030217 neurology & neurosurgery, MESH: Cryptococcosis / microbiology
Abstract: Cryptococcus neoformans is a leading cause of fungal brain infection, but the mechanism of dissemination and dynamics of cerebral infection following pulmonary disease are poorly understood. To address these questions, non-invasive techniques that can study the dynamic processes of disease development and progression in living animal models or patients are required. As such, bioluminescence imaging (BLI) has emerged as a powerful tool to evaluate the spatial and temporal distribution of infection in living animals. We aimed to study the time profile of the dissemination of cryptococcosis from the lung to the brain in murine models by engineering the first bioluminescent C. neoformans KN99α strain, expressing a sequence-optimized red-shifted luciferase. The high pathogen specificity and sensitivity of BLI was complemented by the three-dimensional anatomical information from micro-computed tomography (μCT) of the lung and magnetic resonance imaging (MRI) of the brain. These non-invasive imaging techniques provided longitudinal readouts on the spatial and temporal distribution of infection following intravenous, intranasal or endotracheal routes of inoculation. Furthermore, the imaging results correlated strongly with the fungal load in the respective organs. By obtaining dynamic and quantitative information about the extent and timing of brain infections for individual animals, we found that dissemination to the brain after primary infection of the lung is likely a late-stage event with a timeframe that is variable between animals. This novel tool in Cryptococcus research can aid the identification of host and pathogen factors involved in this process, and supports development of novel preventive or therapeutic approaches., Summary: A novel combination of bioluminescence and anatomical imaging non-invasively identified the timeframe and extent of Cryptococcus neoformans dissemination to the brain in animal models of systemic and pulmonary fungal infection.
Published: 2019

48. Metabolic and innate immune cues merge into a specific inflammatory response via unfolded proteinresponse (UPR)

Author: Mogilenko, Denis, Haas, Joël, L'Homme, Laurent, Fleury, Sébastien, Quemener, Sandrine, Levavasseur, Matthieu, Becquart, Coralie, Wartelle, Julien, Bogomolova, Alexandra, Pineau, Laurent, Molendi-Coste, Olivier, Lancel, Steve, Dehondt, Hélène, Gheeraert, Céline, Melchior, Aurélie, Dewas, Cédric, Nikitin, Artemii, Pic, Samuel, Rabhi, Nabil, Annicotte, Jean-Sébastien, Oyadomari, Seiichi, Velasco-Hernandez, Talia, Cammenga, Jörg, Foretz, Marc, Viollet, Benoit, Vukovic, Milica, Villacreces, Arnaud, Kranc, Kamil, Carmeliet, Peter, Marot, Guillemette, Boulter, Alexis, Tavernier, Simon, Berod, Luciana, Longhi, Maria, Paget, Christophe, Janssens, Sophie, Staumont-Sallé, Delphine, Aksoy, Ezra, Staels, Bart, Dombrowicz, David, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Fujii Memorial Institute of Medical Sciences [Tokushima, Japan] (Institute of Advanced Medical Sciences), Tokushima University, Department of Hematology [Linköping, Sweden] (Institute for Clinical and Experimental Medicine), Linköping University (LIU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Centre for Haemato-Oncology [London, UK] (Barts Cancer Institute), Queen Mary University of London (QMUL), Laboratory of Angiogenesis and Vascular Metabolism [Leuven, Belgium], VIB-KU Leuven Center for Brain & Disease Research [Leuven, Belgium], Laboratory of Angiogenesis and Vascular Metabolism [Leuven, Belgium] (VIB-CCB), Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), MOdel for Data Analysis and Learning (MODAL), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille, Sciences et Technologies, University of Florida [Gainesville] (UF), Unit of Immunoregulation and Mucosal Immunology [Ghent, Belgium], VIB Inflammation Research Center [Ghent, Belgium], Hannover Medical School [Hannover] (MHH), The William Harvey Research Institute [London, UK] (NIHR Barts Biomedical Research Centre), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), ER Stress and Inflammation [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Département de Dermatologie [CHRU Lille], Centre for Biochemical Pharmacology [London, UK] (William Harvey Research Institute), This work was supported in part by grants from ANR and the European Union (EGID ANR-10-LABX-46 to B.S. and D.D. and ANR-17-CE15-0030-02 to B.V.), a National Psoriasis Foundation (USA) Early Career Research Grant (to D.A.M.), an EMBO Long-Term Fellowship (to J.T.H.), an MRC grant (MR/M023230/1 to E.A.), and CRUK grants (C29967/A14633 and C29967/A26787 to K.K.). B.S. is recipient of an ERC advanced grant (ERC-2016-AdG-694717)., We thank members of the Bart Staels lab for help with experiments, Jean-Claude Sirard (Institut Pasteur de Lille, France), Juan R. Cubillos-Ruiz and Laurie H. Glimcher (Weill Cornell Medical College, New York, USA), Eik Hoffmann (Institut Pasteur de Lille, France) for mice, and Morten Danielsen and Lea Johnsen (MS-Omics, Copenhagen, Denmark) for assistance with LC-MS and GC-MS., Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-17-CE15-0030,MetaTreg,Métabolisme cellulaire des Treg dans le controle des maladies inflammatoires chroniques(2017), Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-École polytechnique universitaire de Lille (Polytech Lille), and Dupuis, Christine
Subjects: mtROS, [SDV.IMM] Life Sciences [q-bio]/Immunology, hexokinase, UPR, psoriasis, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, glycolysis, fatty acids, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, IL-23, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, metabolic reprogramming, [SDV.IMM]Life Sciences [q-bio]/Immunology, dendritic cells, innate immunity, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]; International audience; Innate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (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-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR.
Published: 2019

49. Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications

Author: Konstantinos Vlachos, Riccardo Cappato, Isabelle Deisenhofer, Yoshifusa Aizawa, Graham Stuart, Thomas Pambrun, Juan Pablo Kaski, Antonio Frontera, Ivan Blankoff, Pierre Bordachar, Linda Koutbi, Takeshi Kitamura, Daniel Scherr, Nicolas Derval, Patrice Scanu, Gerard J. Fahy, Philippe Ritter, Pascal Defaye, Frederic Sacher, Michel Haïssaguerre, Arnaud Denis, Philippe Maury, Martin Manninger, Alice Maltret, Mélèze Hocini, Christelle Marquié, Jean-Luc Pasquié, Saagar Mahida, Pierre Jaïs, Joris Ector, Xavier Pillois, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Chest Hospital, Hôpital Charles Perrens, Cork University Hospital, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Bristol Heart Institute, Cardiac Stimulation and Rhythmology, CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), UCL Institute of Cardiovascular Science London, Department of Cardiology [K.U.Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospital Gasthuisberg, Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Herzzentrum München, Centre Hospitalier, Division of Cardiology, Niigata University Graduate School of Medical and Dental Science Niigata Japan., Département de cardiologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Toulouse [Toulouse], CHU Necker - Enfants Malades [AP-HP], MORNET, Dominique, Centre hospitalier Charles Perrens [Bordeaux], Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-University Hospital Gasthuisberg [Leuven], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, Cardiac & Cardiovascular Systems, Heart disease, [SDV]Life Sciences [q-bio], Arrhythmias, 030204 cardiovascular system & hematology, Ventricular tachycardia, GUIDELINES, Sudden Cardiac Death, NAV1.5 Voltage-Gated Sodium Channel, Electrocardiography, 0302 clinical medicine, Recurrence, Interquartile range, Arrhythmia and Electrophysiology, Longitudinal Studies, Child, 10. No inequality, Original Research, Hypertrophic cardiomyopathy, Defibrillators, Implantable, 3. Good health, [SDV] Life Sciences [q-bio], Electrophysiology, Natural history, Long QT Syndrome, Phenotype, syncope, Cohort, idiopathic, Female, ventricular tachycardia, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, STANDARDS, medicine.medical_specialty, Adolescent, complications, Long QT syndrome, 03 medical and health sciences, defibrillator, Cardiomyopathy, Hypertrophic, Familial, medicine, Humans, Science & Technology, Myosin Heavy Chains, business.industry, ECG, Ryanodine Receptor Calcium Release Channel, 030208 emergency & critical care medicine, medicine.disease, ventricular fibrillation, Ventricular fibrillation, Tachycardia, Ventricular, Cardiovascular System & Cardiology, business, Cardiac Myosins
Abstract: Background The natural history and long‐term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long‐term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty‐six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow‐up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow‐up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device‐related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long‐term follow‐up. Recurrent VF is common in this patient group.
Published: 2019

50. Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model

Author: Kadiombo Bantubungi, Luc Buée, Anne Tailleux, David Blum, Emmanuelle Vallez, Sylvie Raison, Elodie Marciniak, Didier Vieau, Tariq Ahmed, Raphaëlle Caillierez, Steve Lancel, Detlef Balschun, Antoine Leboucher, Aurelie Joly-Amado, Emilie Caron, Sabiha Eddarkaoui, Kevin Carvalho, Bart Staels, Malika Hamdane, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Excellence Laboratory LabEx DISTALZ, Brain & Cognition [Leuven, Belgium] (Faculty of Psychology & Educational Sciences), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Faculty of Psychology & Educational Sciences [Leuven, Belgium], Neurological Disorders Research Center [Doha, Qatar], Hamad Bin Khalifa University (HBKU)-Qatar Biomedical Research Institute (QBRI), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Pharmacology and Physiology [Tampa, FL, USA] (Byrd Alzheimer’s Institute ), University of South Florida [Tampa] (USF), This work was supported by grants from France Alzheimer/ Fondation de France (InsTauBrain project), FHU VasCog research network (Lille, France) and programs d'investissements d'avenir LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease). Our laboratories are also supported by ANR (GRAND, SPREADTAU to LB, ADORATAU & ADORASTrAU to DB), Fondation pour la Recherche Médicale, Vaincre Alzheimer, Fondation Plan Alzheimer as well as Inserm, CNRS, Université Lille, Lille Métropole Communauté Urbaine, Région Hauts-de-France, DN2M. AL and KC hold a doctoral grant from Lille 2 University. EM hold a doctoral grant from CHRU and Région Hauts de France. D. Balschun is supported by Research Foundation - Flanders (FWO)., ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), ANR-14-CE13-0031,SPREADTAU,Transfert différentiel intercellulaire des assemblages de Tau(2014), ANR-12-MALZ-0001,ADORATAU,Récepteurs A2A et Tauopathie(2012), ANR-18-CE16-0008,ADORASTrAU,Contribution des astrocytes aux troubles cognitifs induits par la protéine Tau neuronale dans la maladie d'Alzheimer(2018), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of South Florida (USF), ANR-11-LABX-0009/11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), ANR-18-CE16-0008,ADORASTRAU,CONTRIBUTION OF ASTROCYTES TO COGNITIVE DEFICITS INDUCED BY NEURONAL TAU IN ALZHEIMER’S DISEASE(2018), Blum, David, Laboratoires d'excellence - Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime - - DISTALZ2011 - ANR-11-LABX-0009 - LABX - VALID, Appel à projets générique - Transfert différentiel intercellulaire des assemblages de Tau - - SPREADTAU2014 - ANR-14-CE13-0031 - Appel à projets générique - VALID, Maladie d'Alzheimer et Maladies Apparentées - Récepteurs A2A et Tauopathie - - ADORATAU2012 - ANR-12-MALZ-0001 - MALZ - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Contribution des astrocytes aux troubles cognitifs induits par la protéine Tau neuronale dans la maladie d'Alzheimer - - ADORASTrAU2018 - ANR-18-CE16-0008 - AAPG2018 - VALID, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie et physiopathologie neuronale, Institut National de la Santé et de la Recherche Médicale (INSERM), Impact de l'Environnement Chimique sur la Santé Humain, PRES Université Lille Nord de France, Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Environnement périnatal et croissance, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratory of Biological Psychology, and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)
Subjects: 0301 basic medicine, Genetically modified mouse, medicine.medical_specialty, Transgene, medicine.medical_treatment, Hippocampus, Mice, Transgenic, tau Proteins, Energy homeostasis, Hypoinsulinemia, lcsh:RC321-571, 03 medical and health sciences, Mice, 0302 clinical medicine, Insulin resistance, Internal medicine, medicine, Animals, Insulin, Transgenic mice, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, ComputingMilieux_MISCELLANEOUS, biology, Brain, THY-Tau22, Alzheimer's disease, medicine.disease, Mice, Inbred C57BL, Insulin receptor, 030104 developmental biology, Endocrinology, Metabolism, Neurology, Tauopathies, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Tau, 030217 neurology & neurosurgery
Abstract: International audience; Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis. Thus, in AD, brain insulin resistance affects both cognitive and metabolic changes described in these patients. While a role of Aβ oligomers and APOE4 towards the development of brain insulin resistance emerged, contribution of Tau pathology has been largely overlooked. Our recent data demonstrated that one of the physiological function of Tau is to sustain brain insulin signaling. We postulated that under pathological conditions, hyper-phosphorylated/aggregated Tau is likely to lose this function and to favor the development of brain insulin resistance. This hypothesis was substantiated by observations from patient brains with pure Tauopathies. To address the potential link between Tau pathology and brain insulin resistance, we have evaluated the brain response to insulin in a transgenic mouse model of AD-like Tau pathology (THY-Tau22). Using electrophysiological and biochemical evaluations, we surprisingly observed that, at a time when Tau pathology and cognitive deficits are overt and obvious, the hippocampus of THY-Tau22 mice exhibits enhanced response to insulin. In addition, we demonstrated that the ability of i.c.v. insulin to promote body weight loss is enhanced in THY-Tau22 mice. In line with this, THY-Tau22 mice exhibited a lower body weight gain, hypoleptinemia and hypoinsulinemia and finally a metabolic resistance to high-fat diet. The present data highlight that the brain of transgenic Tau mice exhibit enhanced brain response to insulin. Whether these observations are ascribed to the development of Tau pathology, and therefore relevant to human Tauopathies, or unexpectedly results from the Tau transgene overexpression is debatable and discussed.
Published: 2019

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