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1. Impact of smoking on cardiovascular risk and premature ageing: Findings from the STANISLAS cohort

Author

Tripti Rastogi, Nicolas Girerd, Zohra Lamiral, Emmanuel Bresso, Erwan Bozec, Jean-Marc Boivin, Patrick Rossignol, Faiez Zannad, João Pedro Ferreira, 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), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), 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), 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 ), The fourth examination of the STANISLAS study was sponsored by the Centre Hospitalier Régional Universitaire of Nancy (CHRU) and the French Ministry of Health (Programme Hospitalier de Recherche Clinique Inter‐régional 2013), by the Contrat de Plan Etat‐ Lorraine and 'Fonds Européen de Développement Régional' (FEDER Lorraine), and by a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' program FIGHT‐HF (reference: ANR‐15‐RHU‐0004) and by the French 'Projet investissement d'avenir' (PIA) project 'Lorraine Université d'Excellence' (reference ANR‐15‐IDEX‐04‐LUE)., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project, European Project: FEDER, BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Contrat de Plan Etat Lorraine IT2MP - INCOMING, and Fonds Européens de Développement Régional - FEDER - INCOMING

Subjects
Aging, circulating protein profile, premature ageing, Carotid Intima Media Thickness, STANISLAS cohort, Smoking, Pulse Wave Analysis, Carotid Intima-Media Thickness, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiovascular Diseases, Heart Disease Risk Factors, Risk Factors, Estimated Glomerular, Humans, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract

International audience; Background and aims: Smoking may lead to premature ageing, but the impact on the cardiovascular system and circulating proteins needs further investigation. In the present study, we aim to understand the impact of smoking on heart and vessels and circulating biomarkers of multiple domains including cardiovascular damage, premature ageing and cancer-related pathways.Methods: The STANISLAS Cohort is a longitudinal familial cohort with detailed cardiovascular examination and biomarker assessment. This study included all the participants enrolled in the fourth visit of the STANISLAS Cohort for whom information on smoking habits was available (n = 1696). We assessed pulse wave velocity, intima-media thickness, echocardiographic parameters and a total of 460 proteins to study the association of circulating plasma proteins with smoking status (never vs. past vs. current smoking) while adjusting for potential confounders.Results: Current smokers were approximately 18 years younger but had higher left ventricular mass index (LVMi) and similar pulse wave velocity (PWV), carotid intima media thickness (cIMT), frequency of hypertension, diabetes and carotid plaques compared to the much older never smokers. After multivariate selection, 25 proteins were independently associated with current or past smoking. Current smoking was strongly associated with higher levels of EDIL-3, CCL11, TNFSF13B, KIT, and lower levels of IL-12B and PLTP (p < 0.0001) while past smoking was associated with FGF-21, CHIT1, and lower levels of CXCL10, IL1RL2 and RAGE (p < 0.01).Conclusions: Current smoking is associated with signs of early onset of cardiovascular ageing and protein biomarkers that regulate inflammation, endothelial function, metabolism, oncological processes and apoptosis.

Published
2022

2. Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor

Author

Jean Personnaz, Enzo Piccolo, Alizée Dortignac, Jason S. Iacovoni, Jérôme Mariette, Vincent Rocher, Arnaud Polizzi, Aurélie Batut, Simon Deleruyelle, Lucas Bourdens, Océane Delos, Lucie Combes-Soia, Romain Paccoud, Elsa Moreau, Frédéric Martins, Thomas Clouaire, Fadila Benhamed, Alexandra Montagner, Walter Wahli, Robert F. Schwabe, Armelle Yart, Isabelle Castan-Laurell, Justine Bertrand-Michel, Odile Burlet-Schiltz, Catherine Postic, Pierre-Damien Denechaud, Cédric Moro, Gaelle Legube, Chih-Hao Lee, Hervé Guillou, Philippe Valet, Cédric Dray, Jean-Philippe Pradère, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SIAAP - Direction du Développement et de la Prospective, SIAAP, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-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), Université de Toulouse (UT)-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 de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Unité de biologie moléculaire, cellulaire et du développement - UMR5077 (MCD), Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), 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), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], Columbia University [New York], MetaToul FluxoMet (TBI-MetaToul), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Harvard T.H. Chan School of Public Health, This study was supported by grants from INSERM, Paul Sabatier University, the Agence Nationale de la Recherche (ANR-17-CE14-0016, to J.-P.P.), and the Région Occitanie and Association Française d’Etude et de Recherche sur l’Obésité (to J.-P.P.). J.P. was supported by a scholarship from Paul Sabatier University. E.P. was supported by a scholarship from Agence Nationale de la Recherche (ANR-17-CE14-0016). R.P. was supported by a scholarship from Région Midi-Pyrénées-INSERM (no. 15050341). O.B.-S. and L.C.-S. and the proteomic facility were supported, in part, by the Région Occitanie, European funds (Fonds Européens de Développement Régional, FEDER), Toulouse Métropole, and the French Ministry of Research with the Investissement d’Avenir Infrastructures Nationales en Biologie et Santé program (ProFI, Proteomics French Infrastructure project, ANR-10-INBS-08), ANR-17-CE14-0016,HOLISTic,Rôle de la protéine HMGB1 au cours du stress metabolique(2017), and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
Fatty Liver, Multidisciplinary, [SDV]Life Sciences [q-bio], Medicine [Science], chemical and pharmacologic phenomena, Lipid Metabolisms
Abstract

Dysregulations of lipid metabolism in the liver may trigger steatosis progression, leading to potentially severe clinical consequences such as nonalcoholic fatty liver diseases (NAFLDs). Molecular mechanisms underlying liver lipogenesis are very complex and fine-tuned by chromatin dynamics and multiple key transcription factors. Here, we demonstrate that the nuclear factor HMGB1 acts as a strong repressor of liver lipogenesis. Mice with liver-specific Hmgb1 deficiency display exacerbated liver steatosis, while Hmgb1-overexpressing mice exhibited a protection from fatty liver progression when subjected to nutritional stress. Global transcriptome and functional analysis revealed that the deletion of Hmgb1 gene enhances LXRα and PPARγ activity. HMGB1 repression is not mediated through nucleosome landscape reorganization but rather via a preferential DNA occupation in a region carrying genes regulated by LXRα and PPARγ. Together, these findings suggest that hepatocellular HMGB1 protects from liver steatosis development. HMGB1 may constitute a new attractive option to therapeutically target the LXRα-PPARγ axis during NAFLD. Published version This study was supported by grants from INSERM, Paul Sabatier University, the Agence Nationale de la Recherche (ANR-17-CE14-0016, to J.-P.P.), and the Région Occitanie and Association Française d’Etude et de Recherche sur l’Obésité (to J.-P.P.). J.P. was supported by a scholarship from Paul Sabatier University. E.P. was supported by a scholarship from Agence Nationale de la Recherche (ANR-17-CE14-0016). R.P. was supported by a scholarship from Région Midi-Pyrénées-INSERM (no. 15050341). O.B.-S. and L.C.-S. and the proteomic facility were supported, in part, by the Région Occitanie, European funds (Fonds Européens de Développement Régional, FEDER), Toulouse Métropole, and the French Ministry of Research with the Investissement d’Avenir Infrastructures Nationales en Biologie et Santé program (ProFI, Proteomics French Infrastructure project, ANR-10-INBS-08).

Published
2022

3. An Interactive Platform for Extracting Gradual Patterns from Multivariate Temporal Data

Author

Lonlac, Jerry, Miras, Yannick, Mazenod, Vincent, Mephu Nguifo, Engelbert, Centre for Digital Systems (CERI SN - IMT Nord Europe), Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Nord Europe), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), and Fonds Européens de Développement Régional (FEDER 2014) - Auvergne Rhône Alpes

Subjects
Pattern mining, Gradual patterns, [SDE]Environmental Sciences, [INFO]Computer Science [cs], Data mining, Temporal data
Abstract

International audience; This paper presents a tool namely Mobipaleo to automatically extract simultaneous attribute co-variations called gradual patterns from multivariate temporal data. It proposes two types of temporal resolution to integrate in the search process according to user preferences: the high temporalresolution taken into account referenced as the temporal constraint between consecutive objects and the low temporal resolution referenced as the temporal constraint between distant objects. Mobipaleo highlights the benefits of using artificial intelligence techniques such as pattern mining in real-world applications.

Published
2021

4. 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

5. 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

6. Amino-acid functionalized porous silicon nanoparticles for the delivery of pDNA

Author

Chaix, Arnaud, Cueto-Diaz, Eduardo, Delalande, Anthony, Knezevic, Nikola, Midoux, Patrick, Durand, Jean-Olivier, Pichon, Chantal, Cunin, Frédérique, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Distributed Programming Laboratory (LPD), Ecole Polytechnique Fédérale de Lausanne (EPFL), The authors gratefully acknowledge the Région Occitanie and the Fonds Européens de Développement Régional (FEDER) for financial support., Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Hennaut, Odile

Subjects
[CHIM] Chemical Sciences, technology, industry, and agriculture, [CHIM]Chemical Sciences, equipment and supplies
Abstract

Porous silicon nanoparticles as a novel platform in gene therapy, have shown to be an efficient vehicle for the delivery of nucleic acids in cells. For the first time, a family of porous silicon nanoparticles has been produced featuring an amino-acid functionalized cationic external surface aiming at pDNA complexation. The amino acid-based pDNA nanocarriers, displaying an average diameter of 295 nm, succeeded in transfection of HEK293 cells with an efficiency 300 times superior to “bare” porous silicon nanoparticles.

Published
2019

7. 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

8. 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

9. Sexual dimorphism in PAR2-dependent regulation of primitive colonic cells

Author

Noguerol, Julie, Roustan, Pierre-Jean, N’Taye, Mikael, Delcombel, Léo, Rolland, Corinne, Guiraud, Laura, Sagnat, David, Edir, Anissa, Bonnart, Chrystelle, Denadai-Souza, Alexandre, Deraison, Céline, Vergnolle, Nathalie, Racaud-Sultan, Claire, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fond Unique Interministeriel (FUI) program by the Région Midi-Pyrénées, the Banque Publique d’Investissement (BPI) de France, Fonds Européens de Développement Régional (FEDER), (ANR-11-EQPX-0003), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Racaud-Sultan, Claire, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, Physiology of the Intestine: Proteases from the Epithelium - PIPE - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 310973 - VALID, Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)

Subjects
Genetics & Heredity, EXPRESSION, HOMEOSTASIS, Science & Technology, Protease-activated receptor, lcsh:QP1-981, lcsh:R, lcsh:Medicine, Biotechnologies, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], lcsh:Physiology, GSK3, Endocrinology & Metabolism, Sexual dimorphism, Médecine vétérinaire et santé animal, Colon primitive cells, ONSET, SURVIVAL, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Veterinary medicine and animal Health, Life Sciences & Biomedicine, STEM-CELLS
Abstract

BACKGROUND: Sexual dimorphism in biological responses is a critical knowledge for therapeutic proposals. However, gender differences in intestinal stem cell physiology have been poorly studied. Given the important role of the protease-activated receptor PAR2 in the control of colon epithelial primitive cells and cell cycle genes, we have performed a sex-based comparison of its expression and of the effects of PAR2 activation or knockout on cell proliferation and survival functions. METHODS: Epithelial primitive cells isolated from colons from male and female mice were cultured as colonoids, and their number and size were measured. PAR2 activation was triggered by the addition of SLIGRL agonist peptide in the culture medium. PAR2-deficient mice were used to study the impact of PAR2 expression on colon epithelial cell culture and gene expression. RESULTS: Colonoids from female mice were more abundant and larger compared to males, and these differences were further increased after PAR2 activation by specific PAR2 agonist peptide. The proliferation of male epithelial cells was lower compared to females but was specifically increased in PAR2 knockout male cells. PAR2 expression was higher in male colon cells compared to females and controlled the gene expression and activation of key negative signals of the primitive cell proliferation. This PAR2-dependent brake on the proliferation of male colon primitive cells was correlated with stress resistance. CONCLUSIONS: Altogether, these data demonstrate that there is a sexual dimorphism in the PAR2-dependent regulation of primitive cells of the colon crypt. ispartof: BIOLOGY OF SEX DIFFERENCES vol:10 issue:1 ispartof: location:England status: published

Published
2019

10. 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

11. Polyphénols extraits de petits fruits et déclin cognitif lié à l’âge : résultats de l’étude Neurophenols

Author

BENSALEM, Julien, Lafenetre, Pauline, Pallet, Véronique, Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Bpifrance, Le conseil régional de Nouvelle Aquitaine, Fonds européens de développement régional (FEDER), Gouvernement de la province de Québec., Nutrition et Neurobiologie intégrée (NutriNeuro), and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique

Subjects
Flavonoids, bleuet, Aging, mice, [SDV]Life Sciences [q-bio], Grape, vieillissement, santé humaine, souris, human health, Blueberry, raisin, polyphénol, flavonoïdes, mémoire, Memory, Nutrition
Abstract

Ce numéro est constitué d’articles issus du colloque « Alimentation périnatale, alimentation des séniors: spécificités, impact du microbiote », organisé le 28 mars 2018 à Paris.; Il est maintenant bien établi que le vieillissement est lié à l’apparition de troubles cognitifs. Ces altérations mnésiques liées à l’âge peuvent être mises en évidence à la fois chez l’Homme et l’animal. Plusieurs études ont évoqué le rôle bénéfique des polyphénols sur les fonctions mnésiques et en particulier sur le déclin cognitif lié à l’âge. Le projet Neurophenols a permis de mettre au point un mélange de polyphénols extraits de raisins et debleuets (PEGB) et d’objectiver son rôle bénéfique sur le déclin cognitif lié à l’âge au niveau préclinique et clinique.Au niveau préclinique, chez la souris, la consommation de PEGB par voie alimentaire permet de normaliser les performances d’apprentissage et de mémoire dépendant de l’hippocampe, altérées au cours du vieillissement. Cet effet bénéfique est aussi mis en évidence sur l’expression de marqueurs moléculaires impliqués dans la plasticité synaptique et la neurogenèse hippocampique, processus qui sous-tendent les processus mnésiques.Ces résultats précliniques prometteurs ont été prolongés par une étude d’intervention nutritionnelle chez l’homme pour l’évaluation des effets de PEGB sur la mémoire de sujets âgés.

Published
2018

12. 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

13. 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

14. La Grive à Pieds Jaunes, Turdus lherminieri (Turdidés): une espèce méconnue à valeur patrimoniale

Author

Arnoux , Emilie, Eraud , Cyril, Garnier , Stéphane, Faivre , Bruno, 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, Projet financé par l'Office National de la Chasse et de la Faune Sauvage (ONCFS), les fonds européens de développement régional (FEDER), le Parc national de la Guadeloupe (PNG), la direction de l'aménagement et du logement de la Guadeloupe (DEAL 971) et le conseil régional de Bourgogne., and Laffont, Rémi

Subjects
[SDE.BE] Environmental Sciences/Biodiversity and Ecology, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Génétique des populations, Abondance, Grive à Pieds Jaunes, Domaine vital
Abstract

10 pages; National audience; Les départements et régions d’Outre-Mer présentent une biodiversité remarquable et un fort taux d’endémisme,mais cet endémisme a pour conséquence une plus grande fragilité et un plus grand risque d’extinction. Les enjeuxde conservation de la biodiversité sont alors importants et l’élaboration de mesures de gestion se heurte biensouvent à une profonde méconnaissance de la biologie des espèces. Dans ce contexte, la Grive à Pieds Jaunes,oiseau endémique de quatre îles des Petites Antilles (statut vulnérable, UICN) est un modèle de choix dans la miseen place de mesures de gestion et de conservation. Les premiers résultats d’un programme d’étude dédié à cetteespèce ont permis d’améliorer les connaissances sur cet oiseau : abondance, répartition, domaines vitaux et fluxde populations.

Published
2013

15. Automatic learning of structural knowledge from geographic information for updating land cover maps

Author

Bayoudh, Meriam, Roux, Emmanuel, Nock, Richard, Richard, Gilles, UMR 228 Espace-Dev, Espace pour le développement, Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Centre de Recherche en Economie, Gestion, Modélisation et Informatique Appliquée (CEREGMIA), Université des Antilles et de la Guyane (UAG), Argumentation, Décision, Raisonnement, Incertitude et Apprentissage (IRIT-ADRIA), 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, Fonds Européens de Développement Régional (FEDER) Région Guyane., Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), and Université de Toulouse (UT)

Subjects
PROGRAMMATION, SYSTEME D'INFORMATION GEOGRAPHIQUE, INDUCTION, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Land cover/use maps, Inductive Logic Programming (ILP), INTELLIGENCE ARTIFICIELLE, [SHS.GEO]Humanities and Social Sciences/Geography, Remote sensing, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], INTERPRETATION D'IMAGE, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Machine learning, LOGICIEL, LITTORAL, PROGRAMMATION LOGIQUE INDUCTIVE, Geographic Information System (GIS), OCCUPATION SPATIALE, CARTOGRAPHIE
Abstract

International audience; The number of satellites and remote sensing sensors devoted to earth observation becomes increasingly high, providing more and more data and especially images. In the same time the access to such a data and to the tools to process them has been considerably improved. In the presence of such data flow - and regarding the necessity to follow up and predict environmental and societal changes in highly dynamic socio-environmental contexts - we need automatic image interpretation methods. This could be accomplished by exploring some strengths of artificial intelligence. Our main idea consists in inducing classification rules that explicitly take into account structural knowledge, using Aleph, an Inductive Logic Programming (ILP) system. We applied our proposed methodology to three land cover/use maps of the French Guiana littoral. One hundred and forty six classification rules were induced for the 39 land-cover classes of the maps. These rules are expressed in first order logic language which make them intelligible and interpretable by non-experts. A ten-fold cross validation gave average values for classification accuracy, specificity and sensibility equal to, respectively, 98.82 %, 99.65% and 70%. The proposed methodology could be valuably exploited to automatically classify new objects and/or help operators using object-based classification procedures.

Published
2012

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