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7 results on '"Fonds Européens de Développement Régional (FEDER)"'

1. Human apolipoprotein C1 transgenesis reduces atherogenesis in hypercholesterolemic rabbits

Author

Erwana Harscoët, Naig Le Guern, Stéphanie Lemaire, Valérie Deckert, Bruno Da Silva, Geneviève Jolivet, Thomas Gautier, Lil Proukhnitzky, Marion Xolin, Amandine Bataille, Laurent Lagrost, Charlène Magnani, Virginie Aires, Louis-Marie Houdebine, David Masson, Guillaume Maquart, Danish Patoli, UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biologie du Développement [IBPS] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the University of Bourgogne Franche-Comté, the Institut National de la Santé et de la Recherche Médicale (INSERM), the Fondation de France [Project Cardio 2013 R13057MM-RAF13002MMA to TG], ANR grant ATHEROLIP, the European Union program FEDER, and by a French Government grant managed by the French National Research Agency under the program ‘Investissements d’Avenir’ [reference ANR-11-LABX-0021 (Lipstic Labex)]., ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), ANR-06-PHYS-0002,ATHEROLIP,Identification et caractérisation des propriétés proathérogènes des protéines plasmatiques de transfert des lipides (CETP et PLTP).(2006), European Project: FEDER, Jolivet, Geneviève, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Physiopathologie des maladies humaines (Physio) - Identification et caractérisation des propriétés proathérogènes des protéines plasmatiques de transfert des lipides (CETP et PLTP). - - ATHEROLIP2006 - ANR-06-PHYS-0002 - PHYSIO - VALID, Fonds Européens de Développement Régional - FEDER - INCOMING, Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biologie du Développement [Paris] (LBD), and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)

Subjects
0301 basic medicine, medicine.medical_specialty, Very low-density lipoprotein, Apolipoprotein B, HDL, Transgene, Apolipoprotein C1, Endogeny, Rabbit, 030204 cardiovascular system & hematology, Transgenic, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], CETP, medicine, Animals, Humans, 2. Zero hunger, Apolipoprotein C-I, biology, Triglyceride, Cholesterol, Cholesterol, HDL, Gene Transfer Techniques, Atherosclerosis, Cholesterol Ester Transfer Proteins, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, carbohydrates (lipids), Transgenesis, 030104 developmental biology, Endocrinology, chemistry, biology.protein, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lipids (amino acids, peptides, and proteins), Rabbits, Cardiology and Cardiovascular Medicine
Abstract

International audience; Background and aims: Apolipoprotein (apo) C1 is a 6.6 kDa protein associated with HDL and VLDL. ApoC1 alters triglyceride clearance, and it also favors cholesterol accumulation in HDL, especially by inhibiting CETP in human plasma. Apart from studies in mice, which lack CETP, the impact of apoC1 on atherosclerosis in animal models expressing CETP, like in humans, is not known. This study aimed at determining the net effect of human apoC1 on atherosclerosis in rabbits, a species with naturally high CETP activity but with endogenous apoC1 without CETP inhibitory potential.Methods: Rabbits expressing a human apoC1 transgene (HuApoC1Tg) were generated and displayed significant amounts of human apoC1 in plasma.Results: After cholesterol feeding, atherosclerosis lesions were significantly less extensive (-22%, p < 0.05) and HDL displayed a reduced ability to serve as CETP substrates (-25%, p < 0.05) in HuApoC1Tg rabbits than in WT littermates. It was associated with rises in plasma HDL cholesterol level and PON-1 activity, and a decrease in the plasma level of the lipid oxidation markers 12(S)-HODE and 8(S)HETE. In chow-fed animals, the level of HDL-cholesterol was also significantly higher in HuApoC1Tg than in WT animals (0.83 ± 0.11 versus 0.73 ± 0.11 mmol/L, respectively, p < 0.05), and it was associated with significantly lower CETP activity (cholesteryl ester transfer rate, -10%, p < 0.05; specific CETP activity, -14%, p < 0.05).Conclusions: Constitutive expression of fully functional human apoC1 in transgenic rabbit attenuates atherosclerosis. It was found to relate, at least in part, to the inhibition of plasma CETP activity and to alterations in plasma HDL.

Published
2021

2. Culture of rabbit caecum organoids by reconstituting the intestinal stem cell niche in vitro with pharmacological inhibitors or L-WRN conditioned medium

Author

Nathalie Vergnolle, Claire Cherbuy, Eloïse Mussard, Géraldine Pascal, Virginie Helies, Martin Beaumont, Aude Rubio, Sylvie Combes, Cécile Pouzet, Sandra Fourre, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), FRAIB-TRI Imaging Platform Facilities, Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INRAE PHASE division ('MiniGut' project), 'Fond Unique Interministeriel' (FUI) program, Banque Publique d’Investissement (BPI) de France, Fonds Européens de Développement Régional (FEDER), the region Occitanie funds, Plateforme TRI FR-AIB, Fédération de Recherche Agrobiosciences, Interactions et Biodiversité (FR AIB), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and SEGUIN, Nathalie

Subjects
0301 basic medicine, Cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Epithelium, Caecum, 03 medical and health sciences, 0302 clinical medicine, medicine, Organoid, Animals, Intestinal Mucosa, Stem Cell Niche, lcsh:QH301-705.5, Cecum, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Enteroid, Barrier function, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Monolayer, Culture medium, Cell Biology, General Medicine, biology.organism_classification, Intestinal epithelium, In vitro, Cell biology, Intestines, Organoids, 030104 developmental biology, medicine.anatomical_structure, Spheroid, lcsh:Biology (General), Culture Media, Conditioned, Rabbits, Stem cell, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Intestinal organoids are self-organized 3-dimensional (3D) structures formed by a single layer of polarized epithelial cells. This innovative in vitro model is highly relevant to study physiology of the intestinal epithelium and its role in nutrition and barrier function. However, this model has never been developed in rabbits, while it would have potential applications for biomedical and veterinary research. Here, we cultured rabbit caecum organoids with either pharmacological inhibitors (2Ki medium) or L-WRN cells conditioned medium (L-WRN CM) to reconstitute the intestinal stem cell niche in vitro. Large spherical organoids were obtained with the 2Ki medium and this morphology was associated with a high level of proliferation and stem cells markers gene expression. In contrast, organoids cultured with L-WRN CM had a smaller diameter; a greater cell height and part of them were not spherical. When the L-WRN CM was used at low concentration (5%) for two days, the gene expression of stem cells and proliferation markers were very low, while absorptive and secretory cells markers and antimicrobial peptides were elevated. Epithelial cells within organoids were polarized in 3D cultures with 2Ki medium or L-WRN CM (apical side towards the lumen). We cultured dissociated organoid cells in 2D monolayers, which allowed accessibility to the apical compartment. Under these conditions, actin stress fibers were observed with the 2Ki medium, while perijonctionnal localization of actin was observed with the L-WRN CM suggesting, in 2D cultures as well, a higher differentiation level in the presence of L-WRN CM. In conclusion, rabbit caecum organoids cultured with the 2Ki medium were more proliferative and less differentiated than organoids cultured with L-WRN CM. We propose that organoids cultured with the 2Ki medium could be used to rapidly generate in vitro a large number of rabbit intestinal epithelial stem cells while organoids cultured with the L-WRN CM used at low concentration represent a suitable model to study differentiated rabbit epithelium.

Published
2020

3. New piperazine multi-effect drugs prevent neurofibrillary degeneration and amyloid deposition, and preserve memory in animal models of Alzheimer's disease

Author

Nicolas Sergeant, Valérie Vingtdeux, Sabiha Eddarkaoui, Marion Gay, Caroline Evrard, Nicolas Le Fur, Cyril Laurent, Raphaelle Caillierez, Hélène Obriot, Paul-Emmanuel Larchanché, Amaury Farce, Mathilde Coevoet, Pascal Carato, Mostafa Kouach, Amandine Descat, Patrick Dallemagne, Valérie Buée-Scherrer, David Blum, Malika Hamdane, Luc Buée, Patricia Melnyk, Equipe Alzheimer and Tauopathies - LilNCog (U1172 Inserm), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), 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 Universitaire de Mesures et d'Analyses [Université de Lille] (CUMA), Université de Lille, Droit et Santé, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), 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, 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), Université de Lille, This work was supported by the Inserm, Lille 2 University and CNRS. Grants were obtained from the FRM Nord Pas-de-Calais (France), ANR, Laboratory of Excellence Labex DISTALZ and France Alzheimer. The 300 MHz NMR facilities were funded by the Région Nord Pas-de-Calais (France), the Ministère de la Jeunesse, de l'Education Nationale et de la Recherche (MJENR) and the Fonds Européens de Développement Régional (FEDER)., ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), 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, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
0301 basic medicine, Plaque, Amyloid, Disease, Piperazines, chemistry.chemical_compound, 0302 clinical medicine, Neurofibrillary degeneration, Amyloid precursor protein, Medicine, media_common, Neurons, biology, Brain, Alzheimer's disease Amyloid Microtubule-associated protein tau Multi-effect drugs Neurofibrillary tangles Tauopathies Acetylcholinesterase, Alzheimer's disease, Acetylcholinesterase, 3. Good health, Neuroprotective Agents, Neurology, Tauopathies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Drug, Neurofibrillary tangles, Amyloid, Microtubule-associated protein tau, media_common.quotation_subject, Mice, Transgenic, Multi effect, Cell Line, lcsh:RC321-571, 03 medical and health sciences, Alzheimer Disease, Memory, Animals, Humans, [CHIM]Chemical Sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, business.industry, Multi-effect drugs, Mice, Inbred C57BL, Piperazine, Disease Models, Animal, 030104 developmental biology, chemistry, Nerve Degeneration, biology.protein, business, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Alzheimer's Disease is a devastating dementing disease involving amyloid deposits, neurofibrillary tangles, progressive and irreversible cognitive impairment. Today, only symptomatic drugs are available and therapeutic treatments, possibly acting at a multiscale level, are thus urgently needed. To that purpose, we designed multi-effects compounds by synthesizing drug candidates derived by substituting a novel N,N'-disubstituted piperazine anti-amyloid scaffold and adding acetylcholinesterase inhibition property. Two compounds were synthesized and evaluated. The most promising hybrid molecule reduces both the amyloid pathology and the Tau pathology as well as the memory impairments in a preclinical model of Alzheimer's disease. In vitro also, the compound reduces the phosphorylation of Tau and inhibits the release of Aβ peptides while preserving the processing of other metabolites of the amyloid precursor protein. We synthetized and tested the first drug capable of ameliorating both the amyloid and Tau pathology in animal models of AD as well as preventing the major brain lesions and associated memory impairments. This work paves the way for future compound medicines against both Alzheimer's-related brain lesions development and the associated cognitive impairments.

Published
2019

4. A fragment-based approach towards the discovery of N-substituted tropinones as inhibitors of Mycobacterium tuberculosis transcriptional regulator EthR2

Author

Marion Flipo, Alexandre Wohlkonig, Florence Leroux, Martin Moune, Abdalkarim Tanina, Baptiste Villemagne, Marilyne Bourotte, Marc Gitzinger, Rosangela Frita, Adrien Herledan, Hugues Prevet, Benoit Deprez, René Wintjens, Christian Kemmer, Alain R. Baulard, Nicolas Willand, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), 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 d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-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, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université libre de Bruxelles (ULB), Bioversys AG [Basel], Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), This work was supported by l’Agence Nationale de la Recherche (ANR), France (Tea-4-Two, ANR-14-CE14-0027-01), PRIM (NewBio4Tb), Institut National de la Santé et de la Recherche Médicale, Université de Lille, Institut Pasteur de Lille, Centre National de la Recherche Scientifique, Région Hauts-de-France (convention no.12000080), and Société d’Accélération du Transfert de Technologie Nord. The NMR facilities were funded by the Région Hauts-de-France (France), the Ministère de la Jeunesse, de l'Education Nationale et de la Recherche (MJENR), the Fonds Européens de Développement Régional (FEDER) and Lille University. René Wintjens is a Research Associate at the Belgian National Fund for Scientific Research (FRS-FNRS)., ANR-14-CE14-0027,Tea-4-Two,Reprogrammation de la bioactivation des thioamides comme alternative antituberculeuse(2014), 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), Department of Bio-engineering Sciences, and Structural Biology Brussels

Subjects
EthR2, Thermal shift assay, Tropinone, Tuberculosis, Drug Evaluation, Preclinical, Computational biology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacologie, Crystallography, X-Ray, 01 natural sciences, Mycobacterium tuberculosis, tropinone, 03 medical and health sciences, ethionamide, Drug Discovery, medicine, Humans, Ethionamide, Pathogen, 030304 developmental biology, 0303 health sciences, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010405 organic chemistry, Chemistry, INHA, Organic Chemistry, General Medicine, Monooxygenase, Prodrug, biology.organism_classification, medicine.disease, fragment-based drug design, 0104 chemical sciences, 3. Good health, Repressor Proteins, Chimie organique, tuberculosis, Fragment-based drug design, pharmacology, medicine.drug, Tropanes
Abstract

Tuberculosis (TB) caused by the pathogen Mycobacterium tuberculosis, represents one of the most challenging threat to public health worldwide, and with the increasing resistance to approved TB drugs, it is needed to develop new strategies to address this issue. Ethionamide is one of the most widely used drugs for the treatment of multidrug-resistant TB. It is a prodrug that requires activation by mycobacterial monooxygenases to inhibit the enoyl-ACP reductase InhA, which is involved in mycolic acid biosynthesis. Very recently, we identified that inhibition of a transcriptional repressor, termed EthR2, derepresses a new bioactivation pathway that results in the boosting of ethionamide activation. Herein, we describe the identification of potent EthR2 inhibitors using fragment-based screening and structure-based optimization. A target-based screening of a fragment library using thermal shift assay followed by X-ray crystallography identified 5 hits. Rapid optimization of the tropinone chemical series led to compounds with improved in vitro potency., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019

5. Habitat specialization predicts genetic response to fragmentation in tropical birds

Author

Marine Bely, Aurélie Khimoun, Cyril Eraud, Anthony Ollivier, Anaïs Charbonnel, Emilie Lefol, Vincent Rocheteau, Bruno Faivre, Marie-Laure Carpentier, Anthony Levesque, Emilie Arnoux, Gilles Leblond, Stéphane Garnier, Martin Delpuech, Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Avifaune Migratrice ( CNERA ), Office National de la Chasse et de la Faune Sauvage, SARL BIOS, Cellule Technique des Antilles Françaises, Office Nationale de la Chasse et de la Faune Sauvage, Financial support from the ERA-Net Net-Biome 2010, the Agence Nationale de la Recherche, the Fundacão para a Ciência e a Tecnologia, the Conseil Régional de la Martinique, the Office National de la Chasse et de la Faune Sauvage (ONCFS), the Fonds Européens de Développement Régional (FEDER), the Guadeloupe National Park (PNG) and the Direction de l’Environnement, de l’Aménagement et du Logement de la Guadeloupe (DEAL 971), and the Conseil Régional de Bourgogne., Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Avifaune Migratrice (CNERA)

Subjects
0106 biological sciences, 0301 basic medicine, Population, Biodiversity, Forests, Biology, Generalist and specialist species, 010603 evolutionary biology, 01 natural sciences, Evolution, Molecular, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Genetics, Animals, population genetic structure, dispersal, education, Guadeloupe, Ecosystem, Ecology, Evolution, Behavior and Systematics, Tropical Climate, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, education.field_of_study, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Habitat fragmentation, Ecology, habitat patchiness, Fragmentation (computing), 15. Life on land, [ SDV.EE.ECO ] Life Sciences [q-bio]/Ecology, environment/Ecosystems, small spatial scale, [ SDV.GEN.GPO ] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Genetics, Population, 030104 developmental biology, Habitat, birds, Biological dispersal, habitat fragmentation, Conservation biology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract

14 pages; International audience; Habitat fragmentation is one of the most severe threats to biodiversity as it may lead to changes in population genetic structure, with ultimate modifications of species evolutionary potential and local extinctions. Nonetheless, fragmentation does not equally affect all species and identifying which ecological traits are related to species sensitivity to habitat fragmentation could help prioritization of conservation efforts. Despite the theoretical link between species ecology and extinction proneness, comparative studies explicitly testing the hypothesis that particular ecological traits underlies species-specific population structure are rare. Here, we used a comparative approach on eight bird species, co-occurring across the same fragmented landscape. For each species, we quantified relative levels of forest specialization and genetic differentiation among populations. To test the link between forest specialization and susceptibility to forest fragmentation, we assessed species responses to fragmentation by comparing levels of genetic differentiation between continuous and fragmented forest landscapes. Our results revealed a significant and substantial population structure at a very small spatial scale for mobile organisms such as birds. More importantly, we found that specialist species are more affected by forest fragmentation than generalist ones. Finally, our results suggest that even a simple habitat specialization index can be a satisfying predictor of genetic and demographic consequences of habitat fragmentation, providing a reliable practical and quantitative tool for conservation biology.

Published
2016

6. Identification of a New Benzimidazole Derivative as an Antiviral against Hepatitis C Virus

Author

Arielle R. Rosenberg, Yves Rouillé, Laurence Cocquerel, Czeslaw Wychowski, Thibaut Vausselin, Adeline Danneels, Ahmed Atef Ahmed Abouzeid Mesalam, Matthieu Lemasson, Sandrine Belouzard, Karin Séron, Muriel Lavie, Jean Dubuisson, Patricia Melnyk, Lucie Fénéant, Lander Foquet, Philip Meuleman, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), 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 National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), Université Paris Descartes - Paris 5 (UPD5), 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, This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), the ANR through ERA-NET Infect-ERA program (ANR-13-IFEC-0002-01). Philip Meuleman was supported by Ghent University (Concerted Action Grant 01G01712) and the Belgian Science Policy Office (BELSPO, IUAP P7/47-HEPRO-2). Thibaut Vausselin and Matthieu Lemasson were supported by a fellowship from the ANRS. Sandrine Belouzard was supported by a Marie Curie International Reintegration Grant (PIRG-GA-2009-256300). Ahmed Atef Mesalam is the recipient of a Ph.D. fellowship provided by the Egyptian Government. The 300-MHz NMR facilities were funded by the Région Nord-Pas de Calais (France), the Ministère de la Jeunesse, de l'Education Nationale et de la Recherche (MJENR), and the Fonds Européens de Développement Régional (FEDER)., We thank P.-E. Larchanché for the synthesis of the compounds. We are grateful to Gilles Duverlie and Véronique Descamps for core protein quantification. We thank Laure Saas for technical assistance. We are also grateful to R. Bartenschlager, C. Biot, J. Bukh, F.L. Cosset, P. Halfon, J. McKeating, and T. Wakita for providing essential reagents. The immunofluorescence analyses were performed with the help of the imaging core facility of the BioImaging Center Lille Nord-de-France., ANR-13-IFEC-0002,HCV-ASSEMBLY,Identification of host factors involved in Hepatitis C Virus assembly and characterization of their potential role in vivo(2013), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-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, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universiteit Gent = Ghent University [Belgium] (UGENT), 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)-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), Universiteit Gent = Ghent University (UGENT), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), and Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille

Subjects
Models, Molecular, 0301 basic medicine, Hepacivirus, Hepatitis C virus, Immunology, Drug Evaluation, Preclinical, Mutation, Missense, Mice, SCID, Drug resistance, Pharmacology, medicine.disease_cause, Antiviral Agents, Microbiology, Virus, Mice, 03 medical and health sciences, Viral Envelope Proteins, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Viral entry, Virology, Vaccines and Antiviral Agents, Drug Resistance, Viral, medicine, Animals, Humans, Cells, Cultured, Mutation, Molecular Structure, biology, Hepatitis C, Virus Internalization, biology.organism_classification, Resistance mutation, medicine.disease, Reverse Genetics, 3. Good health, Disease Models, Animal, Treatment Outcome, 030104 developmental biology, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Aminoquinolines, Hepatocytes
Abstract

Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecules from three different families of compounds, and we identified anti-HCV activity in cell culture for six of them. Of these, we selected a compound (B5) that is currently ending clinical phase I evaluation for neurodegenerative diseases. In hepatoma cells, B5 inhibited HCV infection in a pangenotypic and dose-dependent manner, and its antiviral activity was confirmed in primary hepatocytes. B5 also inhibited infection by pseudoparticles expressing HCV envelope glycoproteins E1 and E2, and we demonstrated that it affects a postattachment stage of the entry step. Virus with resistance to B5 was selected by sequential passage in the presence of the drug, and reverse genetics experiments indicated that resistance was conferred mainly by a single mutation in the putative fusion peptide of E1 envelope glycoprotein (F291I). Furthermore, analyses of the effects of other closely related compounds on the B5-resistant mutant suggest that B5 shares a mode of action with other 4-aminoquinoline-based molecules. Finally, mice with humanized liver that were treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle. IMPORTANCE In the last 4 years, HCV therapy has been profoundly improved with the approval of direct-acting antivirals in clinical practice. Nevertheless, the high costs of these drugs limit access to therapy in most countries. The present study reports the identification and characterization of a compound (B5) that inhibits HCV propagation in cell culture and is currently ending clinical phase I evaluation for neurodegenerative diseases. This molecule inhibits the HCV life cycle by blocking virus entry. Interestingly, after selection of drug-resistant virus, a resistance mutation in the putative fusion peptide of E1 envelope glycoprotein was identified, indicating that B5 could be used to further investigate the fusion mechanism. Furthermore, mice with humanized liver treated with B5 showed a delay in the kinetics of the viral infection. In conclusion, B5 is a novel interesting anti-HCV molecule that could be used to decipher the early steps of the HCV life cycle.

Published
2016

7. Phenotypic variation of Forest Thrushes Turdus lherminieri in Guadeloupe: evidence for geographic differentiation at fine spatial scale

Author

François Cavallo, Bruno Faivre, Stéphane Garnier, Cyril Eraud, Emilie Arnoux, Alban Thomas, Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), CNERA Avifaune migratrice - Station de Chizé, Office National de la Chasse et de la Faune Sauvage, Financial support provided by the Office National de la Chasse et de la Faune Sauvage (ONCFS), the Fonds Européens de Développement Régional (FEDER), the Guadeloupe National Park (PNG), the Direction de l'Environnement, de l'Aménagement et du Logement de la Guadeloupe (DEAL 971), the Conseil Régional de Bourgogne, and the ERA-Net Net-Biome and the Agence Nationale de la Recherche., Biogéosciences [UMR 6282] [Dijon] (BGS), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Morphology, Population, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Conservation, 010603 evolutionary biology, 01 natural sciences, Forest thrush, Divergence, Gene flow, 03 medical and health sciences, Population differentiation, Fine spatial scale, education, 030304 developmental biology, [ SDV.BID ] Life Sciences [q-bio]/Biodiversity, 0303 health sciences, Phenotypic plasticity, education.field_of_study, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, biology, Ecology, Turdus lherminieri, 15. Life on land, biology.organism_classification, Spatial ecology, Biological dispersal, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Scale (map)
Abstract

9 pages; International audience; Spatial differentiation in avian models has been extensively studied at a coarse scale for both theoretical and conservation purposes. Yet, studies at a finer spatial scale are also particularly relevant in birds because their dispersal ability may be much more reduced than expected. In the Forest Thrush Turdus lherminieri, we studied morphological characters commonly used to assess differentiation because they mirror both demographic and selective processes. The Forest Thrush is an endemic and vulnerable Antillean bird species which has dramatically declined in the last 15 years, and whose population functioning and structure remain unknown. We compared birds from 11 sites in Guadeloupe, which were distributed from 2 to 42 km apart over the two main geographic zones of the island (i.e. Grande-Terre and Basse-Terre). Using two synthetic descriptors (for body size and feather size), we detected a strong micro-geographic differentiation between Forest thrush populations for the body-size descriptor but not for the feather-size descriptor. Both males and females were significantly larger in Basse-Terre than in Grande- Terre despite the fine geographic scale. Several hypotheses could explain these results: (i) geographic isolation and differentiation caused by (1)absence of gene flow, (2) phenotypic plasticity, or (3) divergence with gene flow. Although further investigation is needed to identify the exact process generating phenotypic divergence, our study provides a first highlight to the high local variability of this species.

Published
2013

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