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358 results on '"Région Pays de la Loire"'

101. Stable and Local Reservoirs of Mycobacterium ulcerans Inferred from the Nonrandom Distribution of Bacterial Genotypes, Benin

Author

Télésphore Yao Brou, Estelle Marion, Ronald Gnimavo, Marie Kempf, Alban Besnard, Céline Bris, Roch Christian Johnson, Clement Coudereau, Fida Khater, Sara Eyangoh, Marie Robbe-Saule, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Fondation Raoul Follereau [Paris], Maison de la Télédétection, Centre de diagnostic et de traitement de la lèpre et de l’Ulcère de Buruli Madeleine et Raoul Follereau [Pobè, Bénin], Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Fondation Raoul FollereauINSERMAgence Nationale de la Recherche Région Pays de la Loire, ANR-11-CEPL-0007,EXTRA-MU,Etudes multidisciplinaires de l'Expansion et de la Transmission de Mycobacterium ulcerans liées aux changements environnementaux(2011), KEMPF, Marie, Changements Environnementaux Planétaires et Sociétés - Etudes multidisciplinaires de l'Expansion et de la Transmission de Mycobacterium ulcerans liées aux changements environnementaux - - EXTRA-MU2011 - ANR-11-CEPL-0007 - CEP&S - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), and Université d’Abomey-Calavi (UAC)

Subjects
Buruli ulcer, Stable and Local Reservoirs of Mycobacterium ulcerans Inferred from the Nonrandom Distribution of Bacterial Genotypes, Benin, Epidemiology, lcsh:Medicine, Distribution (economics), 0302 clinical medicine, Genotype, Benin, 030212 general & internal medicine, bacteria, 2. Zero hunger, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, Ecology, genetic diversity, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Phylogeography, Infectious Diseases, Mycobacterium ulcerans, Water Microbiology, geospatial model, DNA, Bacterial, Microbiology (medical), 030231 tropical medicine, Nigeria, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, mutational profiling, medicine, Humans, lcsh:RC109-216, Genotyping, 030304 developmental biology, Disease Reservoirs, Genetic diversity, business.industry, Research, lcsh:R, Tropical disease, 15. Life on land, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, tuberculosis and other mycobacteria, genotyping, genomic analysis, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract

International audience; Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts to tackle Buruli ulcer epidemics, the environmental reservoir of its pathogen remains elusive, underscoring the need for new approaches to improving disease prevention and management. In our study, we implemented a local-scale spatial clustering model and deciphered the genetic diversity of the bacteria in a small area of Benin where Buruli ulcer is endemic. Using 179 strain samples from West Africa, we conducted a phylogeographic analysis combining whole-genome sequencing with spatial scan statistics. The 8 distinct genotypes we identified were by no means randomly spread over the studied area. Instead, they were divided into 3 different geographic clusters, associated with landscape characteristics. Our results highlight the ability of M. ulcerans to evolve independently and differentially depending on location in a specific ecologic reservoir.

Published
2020

102. Characterization of Rat ILCs Reveals ILC2 as the Dominant Intestinal Subset

Author

Ahmed Abidi, Thomas Laurent, Gaëlle Bériou, Laurence Bouchet-Delbos, Cynthia Fourgeux, Cédric Louvet, Raja Triki-Marrakchi, Jeremie Poschmann, Régis Josien, Jérôme Martin, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Tunis - El Manar II, Université de Tunis El Manar (UTM), École Centrale de Nantes (ECN), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d’Immunologie, Centre d’Immunomonitorage Nantes Atlantique (CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), This work was realized in the context of IHU-CESTI project that received French government financial support managed by the National Research Agency (ANR). This work was also supported by the Région Pays de la Loire. AA was supported by a FrenchTunisian PHU-UTIQUE grant from the 2015 Hubert Curien program (CMCU N◦15G0809)., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, and University of Tunis El Manar

Subjects
Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, innate lymphoid cells, Cell Count, Biology, Flow cytometry, ILC2, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, Th2 Cells, 0302 clinical medicine, Intestinal mucosa, medicine, Animals, Humans, Immunology and Allergy, Mesenteric lymph nodes, rat, Lymphocytes, Intestinal Mucosa, Receptor, skin and connective tissue diseases, intestine, Cells, Cultured, Original Research, medicine.diagnostic_test, Innate lymphoid cell, Flow Cytometry, Phenotype, Immunity, Innate, Lymphocyte Subsets, Rats, Cell biology, Peyer Patch, [SDV] Life Sciences [q-bio], body regions, 030104 developmental biology, medicine.anatomical_structure, Cytokine, secondary lymphoid organs, Cytokines, lcsh:RC581-607, 030215 immunology
Abstract

International audience; Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that lack antigen-specific receptors and exhibit innate effector functions such as cytokine production that play an important role in immediate responses to pathogens especially at mucosal sites. Mouse and human ILC subsets have been extensively characterized in various tissues and in blood. In this study, we present the first characterization of ILCs and ILC subsets in rat gut and secondary lymphoid organs using flow cytometry and single cell RNA sequencing. Our results show that phenotype and function of rat ILC subsets are conserved as compared to human and mouse ILCs. However, and in contrast to human and mouse, our study unexpectedly revealed that ILC2 and not ILC3 was the dominant ILC subset in the rat intestinal lamina propria. ILC2 predominance in the gut was independent of rat strain, sex or housing facility. In contrast, ILC3 was the predominant ILC subset in mesenteric lymph nodes and Peyer patches. In conclusion, our study demonstrates that in spite of highly conserved phenotype and function between mice, rat and humans, the distribution of ILC subsets in the intestinal mucosa is dependent on the species likely in response to both genetic and environmental factors.

Published
2020

103. A glance into the evolution of template-free protein structure prediction methodologies

Author

Frédéric Cadet, Ramanathan Sowdhamini, Bernard Offmann, Surbhi Dhingra, OFFMANN, Bernard, Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Tata Institute for Fundamental Research (TIFR), National Centre for Biological Sciences [TIFR] (NCBS), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Université de La Réunion - Faculté des Sciences et Technologies (FST), Université de La Réunion (UR), Région Pays de la Loire, projet GRIOTE, Conseil Régional de La Réunion and Fonds Social Européen, PhD scholarship tier 234275, convention DIRED/20161451, and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP)

Subjects
0301 basic medicine, Models, Molecular, ab-initio, Protein Folding, template-free modelling, Computer science, Protein Conformation, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Ab initio, Machine learning, computer.software_genre, Biochemistry, Quantitative Biology - Quantitative Methods, Field (computer science), 03 medical and health sciences, Protein structure, CASP, Databases, Protein, Quantitative Methods (q-bio.QM), Structure (mathematical logic), Template free, 030102 biochemistry & molecular biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Computational Biology, Proteins, Biomolecules (q-bio.BM), General Medicine, Protein structure prediction, artificial intelligence, protein structure prediction, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, 030104 developmental biology, Quantitative Biology - Biomolecules, FOS: Biological sciences, Artificial intelligence, business, computer, Algorithms
Abstract

Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (> 150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep learning approaches to construct protein backbone structure from its amino acid sequence. This review highlights the major strategies undertaken for template-free modelling of protein structures while discussing few tools developed under each strategy. It will also briefly comment on the progress observed in the field of ab initio modelling of proteins over the course of time as seen through the evolution of CASP platform., 17 pages, 1 figure, 1 table

Published
2020

104. Anti-PD1 therapy induces lymphocyte-derived exosomal miRNA-4315 release inhibiting Bim-mediated apoptosis of tumor cells

Author

Nina Guyon, Delphine Garnier, Joséphine Briand, Arulraj Nadaradjane, Gwenola Bougras-Cartron, Judith Raimbourg, Mario Campone, Dominique Heymann, François M. Vallette, Jean-Sébastien Frenel, Pierre-François Cartron, Bernardo, Elizabeth, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Cancéropôle Grand-Ouest [Bretagne-Centre-Pays de Loire], EpiSAVMEN Network (Région Pays de la Loire) [Saint-Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Sulfonamides, Aniline Compounds, Bcl-2-Like Protein 11, Cell Death, lcsh:Cytology, T-Lymphocytes, Programmed Cell Death 1 Receptor, Mice, Nude, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Exosomes, Article, MicroRNAs, Phenotype, [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Resistance, Neoplasm, Cell Line, Tumor, Neoplasms, miRNAs, Biomarkers, Tumor, Temozolomide, Animals, Humans, lcsh:QH573-671, Cancer
Abstract

International audience; Anti-PD1 immunotherapy, as a single agent or in combination with standard chemotherapies, has significantly improved the outcome of many patients with cancers. However, resistance to anti-PD1 antibodies often decreases the long-term therapeutic benefits. Despite this observation in clinical practice, the molecular mechanisms associated with resistance to anti-PD1 antibody therapy have not yet been elucidated. To identify the mechanisms of resistance associated with anti-PD1 antibody therapy, we developed cellular models including purified T cells and different cancer cell lines from glioblastoma, lung adenocarcinoma, breast cancer and ovarian carcinoma. A murine model of lung cancer was also used. Longitudinal blood samples of patients treated with anti-PD1 therapy were also used to perform a proof-of-concept study of our findings. We found that anti-PD1 exposure of T-cell promotes an enrichment of exosomal miRNA-4315. We also noted that exosomal miRNA-4315 induced a phenomenon of apopto-resistance to conventional chemotherapies in cancer cells receiving exosomal miRNA-4315. At molecular level, we discern that the apopto-resistance phenomenon was associated with the miRNA-4315-mediated downregulation of Bim, a proapoptotic protein. In cellular and mice models, we observed that the BH3 mimetic agent ABT263 circumvented this resistance. A longitudinal study using patient blood showed that miRNA-4315 and cytochrome c can be used to define the time period during which the addition of ABT263 therapy may effectively increase cancer cell death and bypass anti-PD1 resistance.This work provides a blood biomarker (exosomal miRNA-4315) for patient stratification developing a phenomenon of resistance to anti-PD1 antibody therapy and also identifies a therapeutic alternative (the use of a BH3 mimetic drug) to limit this resistance phenomenon.

Published
2020

105. An efficient finite element based multigrid method for simulations of the mechanical behavior of heterogeneous materials using CT images

Author

Philippe Sainsot, Julien Réthoré, Xiaodong Liu, Antonius Lubrecht, Marie-Christine Baietto, Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Mécanique Multiéchelle pour les solides (MIMESIS), Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Tribologie et Mécanique des Interfaces (TMI), and Région Pays de la Loire, Nantes Métropole, ConnectTalent IDS

Subjects
Computer simulation, Computer science, Applied Mathematics, Mechanical Engineering, Computational Mechanics, Ocean Engineering, 02 engineering and technology, Degrees of freedom (mechanics), 01 natural sciences, Finite element method, Microscopic scale, Computational science, 010101 applied mathematics, Computational Mathematics, Matrix (mathematics), 020303 mechanical engineering & transports, Multigrid method, 0203 mechanical engineering, Computational Theory and Mathematics, Convergence (routing), [PHYS.MECA.SOLID]Physics [physics]/Mechanics [physics]/Solid mechanics [physics.class-ph], Tomography, 0101 mathematics
Abstract

International audience; X-ray tomography techniques give researchers the full access to material inner structures. With such ample information, employing numerical simulation on real material images becomes more and more common. Material behavior, especially, of heterogeneous materials, e.g. polycrystalline, composite, can be observed at the microscopic scale with the computed tomography (CT) techniques. In this work, an efficient strategy is proposed to carry out simulations on large 3D CT images. A proposed matrix free type finite element based MultiGrid method is applied to improve convergence speed and to reduce memory space requirements. Homogeniza-tion techniques are used to obtain specific operators to enhance the convergence of the MultiGrid method when large material property variations are present. Hybrid parallel computing is implemented for memory space and computing time reasons. Free edge effects in a laminate composite with more than 16 billion degrees of freedom and crack opening in a cast iron are studied using the proposed strategy.

Published
2020

106. Simultaneous exploration of nutrients and pollutants in human milk and their impact on preterm infant growth: An integrative cross-platform approach

Author

Marie-Cécile Alexandre-Gouabau, Jean-Philippe Antignac, German Cano-Sancho, Dominique Darmaun, Yann Guitton, Anne-Lise Royer, Thomas Moyon, Bruno Le Bizec, Jean-Christophe Rozé, Clair-Yves Boquien, Hélène Billard, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), European Milk Bank Association [Milan, Italie] (EMBA), Région Pays-de-la-Loire, France, (2011–2012), and Fonds Européen de Développement Economique et Régional (FEDER, France, Grant 38395, Project 6226, 2013–2015)

Subjects
Exposome, Biomarkers Nutrients, Breast milk, Pilot Projects, 010501 environmental sciences, Biology, 01 natural sciences, Biochemistry, 03 medical and health sciences, Child Development, 0302 clinical medicine, Nutrient, Environmental health, Bayesian multivariate linear regression, Humans, 030212 general & internal medicine, Infant Nutritional Physiological Phenomena, 0105 earth and related environmental sciences, General Environmental Science, 2. Zero hunger, Pollutant, Milk, Human, Confounding, Infant, Newborn, Infant, Preterm infants, Nutrients, Growth model, [SDE.ES]Environmental Sciences/Environmental and Society, 3. Good health, Risk-benefit assessment, Persistent pollutants, Environmental Pollutants, Molecular Profile, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Infant, Premature
Abstract

International audience; Early nutritional management including fortified human breastmilk is currently recommended to fulfil the energy demands and counterbalance risks associated to preterm birth. However, little is known about the potential adverse effects of exposure to persistent organic pollutants (POPs) carried in human milk on preterm infant growth. We conducted a pilot study proving the application of an integrative analytical approach based on mass spectrometry (MS) coupled to advanced statistical models, favouring the comprehensive molecular profiling to support the identification of multiple biomarkers. We applied this workflow in the frame of a preterm infants’ cohort to explore environmental determinants of growth. The combination of high resolution gas and liquid chromatography MS platforms generated a large molecular profile, including 102 pollutants and nutrients (targeted analysis) and 784 metabolites (non-targeted analysis). Data analysis consisted in a preliminary examination of associations between the signatures of POPs and the normalised growth of preterm infants, using multivariate linear regression adjusting for known confounding variables. A second analysis aimed to identify multidimensional biomarkers using a multiblock algorithm allowing the integration of multiple datasets in the growth model of preterm infants. The preliminary results did not suggest an impairment of preterm growth associated to the milk concentrations of POPs. The multiblock approach however revealed complex interrelated molecular networks of POPs, lipids, metabolites and amino acids in breastmilk associated to preterm infant growth, supporting the high potential of biomarkers exploration of this proposed workflow. Whereas the present study intended to identify simultaneously pollutant and nutrient exposure profiles associated to early preterm infant growth, this workflow may be easily adapted and applied to other matrices (e.g. serum) and research settings, favouring the functional exploration of environmental determinants of complex and multifactorial diseases.

Published
2020

107. Urine-derived cells provide a readily accessible cell type for feeder-free mRNA reprogramming

Author

Laurent David, Léa Flippe, Amandine Caillaud, Quentin Francheteau, Karim Si-Tayeb, Sebastian Knöbel, Anne Gaignerie, A Derevier, M Rousselle, V Forest-Choquet, N Lefort, F Chaubron, Aurore Girardeau, Caroline Chariau, Valentin François-Campion, Nathalie Gaborit, Plate-forme Cellules souches pluripotentes induites - iPSC [Nantes] (CHU Nantes/INSERM/CNRS-IFR Santé François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Structure Fédérative de Recherche en Santé François Bonamy (SFR RSFB), IPS Platform [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Institut Clinident [Aix en Provence], Miltenyi Biotec GmbH [Bergisch Gladbach, Germany], Région Pays de la Loire., The national project CHOPIN (CHolesterol Personalized INnovation)., ANR-14-CE16-0026,StemHepTher,Validation pré-clinique des hépatocytes dérivés de cellules souches pluripotentes pour la biothérapie hépatique(2014), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), Le Bihan, Sylvie, Appel à projets générique - Validation pré-clinique des hépatocytes dérivés de cellules souches pluripotentes pour la biothérapie hépatique - - StemHepTher2014 - ANR-14-CE16-0026 - Appel à projets générique - VALID, CHOPIN - - CHOPIN2016 - ANR-16-RHUS-0007 - RHUS - VALID, Unité de recherche de l'institut du thorax (ITX-lab), LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)

Subjects
0301 basic medicine, Cell type, Somatic cell, Cellular differentiation, Induced Pluripotent Stem Cells, lcsh:Medicine, Biology, Urine, Cell Line, 03 medical and health sciences, Humans, RNA, Messenger, Induced pluripotent stem cell, lcsh:Science, Dental Pulp, Messenger RNA, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:R, Translation (biology), Cell Differentiation, Fibroblasts, Cellular Reprogramming, 3. Good health, Cell biology, 030104 developmental biology, Cell culture, lcsh:Q, Reprogramming, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Over a decade after their discovery, induced pluripotent stem cells (iPSCs) have become a major biological model. The iPSC technology allows generation of pluripotent stem cells from somatic cells bearing any genomic background. The challenge ahead of us is to translate human iPSCs (hiPSCs) protocols into clinical treatment. To do so, we need to improve the quality of hiPSCs produced. In this study we report the reprogramming of multiple patient urine-derived cell lines with mRNA reprogramming, which, to date, is one of the fastest and most faithful reprogramming method. We show that mRNA reprogramming efficiently generates hiPSCs from urine-derived cells. Moreover, we were able to generate feeder-free bulk hiPSCs lines that did not display genomic abnormalities. Altogether, this reprogramming method will contribute to accelerating the translation of hiPSCs to therapeutic applications.

Published
2018

108. The acquired resistance of mammary cancer cells to CDK4/6 inhibitors drives a DNA methylation reprogramming of genes encoding for BCL2 family members that confers a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug

Author

FRENEL, JEAN-SEBASTIEN, Voisin, Deborah, Nadaradjane, Arulraj, Bougras-Catron, Gwenola, Campone, Mario, Serandour, Aurelien, Cartron, Pierre-Francois, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Biologie des Cancers et de Théranostic [St Herblain, Nantes] (LabCT), UNICANCER-UNICANCER, Epigénétique - Santé - AgroAlimentaire - Végétal - Mer - Environnement - Nutrition [Nantes] (EpiSAVMEN), Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, biological phenomena, cell phenomena, and immunity, neoplasms
Abstract

International audience; Introduction. Due to the aberrant deregulation of the CDK4/6-INK4-RB pathway in breast cancer, CDK4/6 inhibitors are now a cornerstone of first line treatment of metastatic breast cancer showing an increase of progression free survival and overall survival. However, resistance to treatment eventually occur. We aimed at deciphering the molecular mechanisms of resistance to CDK4-6 inhibitors and at evaluating associations of therapies that could restore the sensitivity to the treatment. Methods. To identify potential DNA methylation signatures associated with the acquired resistance to CDK4/6 inhibitors, we established a MCF7 model, resistant to CDK4/6 inhibitors that we also used in Swiss nude mice via xenograft experiments. qMSRE were used to analyze the methylation status of genes encoding for BCL2 family members in cells, but also on circulating tumor DNA (ctDNA) in our in vivo model. Results. Using acquired resistant MCF7 cells to CDK4/6 inhibitors, our work demonstrate that these cells harbor a phenotype of high apopto-sensitivity induced by a BH3-mimetic drug. We next discern that DNMT3A and TET2 are the molecular determinants of this phenomenon via the epigenetic modulation of DNA methylation profile of genes encoding for BCL2 family. Using in vivo model, we noted that the ctDNA dynamic of the DNA methylation level of genes encoding for BCL2 family members is associated with the emergence of the resistance to CDK4/6 inhibitor demonstrated by the absence of tumor growth inhibition. Our experiments also indicated that the administration of a BH3-minetic drug at this time point restores the inhibition of tumor growth. Conclusion. This work provides the evidence that epigenetic modulation (methylation level) of key genes detected in ctDNA is associated with resistance to CDK4-6 inhibitors. The BH3-mimetic drugs are seem really appealing in that context.

Published
2019

109. Diuron modulates the DNA methylation status of the ILT7 and TRAIL/TNFSF10 genes and decreases the killing activity of plasmacytoid dendritic cells

Author

Briand, Josephine, Joalland, Marie-Pierre, Nadaradjane, Arulraj, Bougras-Cartron, Gwenola, Olivier, Christophe, Vallette, François, Perruche, Sylvain, Cartron, Pierre-Francois, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Réseau Epigénétique du Cancéropôle Grand-Ouest [Nantes] (REpiCGO), Cancéropôle Grand Ouest [Nantes]-Maison de la Recherche en Santé [Nantes], Epigénétique - Santé - AgroAlimentaire - Végétal - Mer - Environnement - Nutrition [Nantes] (EpiSAVMEN), Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], LabEX IGO Immunothérapie Grand Ouest, Service de pharmacologie et de Toxicologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
TET2, DNA methylation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Plasmacytoid dendritic cells, Diuron, hemic and immune systems, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances
Abstract

International audience; Background: Plasmacytoid dendritic cell (pDC) is described as the Swiss knife of immune system. Thus, the understanding of aberrant epigenetic reprogramming of genes governing the pDC functionality by pollutants appears such as an attractive research point. Results: Our study has investigated the effect of Diuron (an herbicide) on the pDC-killing activity towards cancer cells. Thus, we observed that the Diuron exposure of pDC promotes a context of global DNA hypomethylation, which is associated with a phenotype of decrease of the killing activity of pDC towards cancer cells. At molecular level, our data associated the Diuron-induced global DNA hypomethylation with the elevated expression of TET2, an epigenetic player involved in DNA demethylation processes, and the decrease of the pDC-killing activity with the decrease of TRAIL expression and the increase of ILT7 expression. Conclusions: Thus, our article reports that a pollutant (Diuron) induces an epigenetic reprogramming of a subtype of immune cell (pDC), which decreases its killing activity towards tumors cells. In some context, this mechanism might be conducive to the initiation of pathologies. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Published
2019

110. Subwavelength Interferometric Control of Absorption in Three-port Acoustic Network

Author

Olivier Richoux, Ioannis Brouzos, Vassos Achilleos, Georgios Theocharis, Laboratoire d'Acoustique de l'Université du Mans (LAUM), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), Department of Physics [Athens], National and Kapodistrian University of Athens (NKUA), and Projet Région Pays de la Loire - Le Mans Acoustique - APAMAS

Subjects
[PHYS.PHYS.PHYS-CLASS-PH]Physics [physics]/Physics [physics]/Classical Physics [physics.class-ph], Phase (waves), FOS: Physical sciences, lcsh:Medicine, Port (circuit theory), Physics - Classical Physics, Applied Physics (physics.app-ph), 02 engineering and technology, 01 natural sciences, Article, Optics, 0103 physical sciences, 010306 general physics, Absorption (electromagnetic radiation), lcsh:Science, [PHYS.MECA.VIBR]Physics [physics]/Mechanics [physics]/Vibrations [physics.class-ph], Physics, SOUND, Multidisciplinary, BROAD-BAND, PERFECT, business.industry, lcsh:R, Classical Physics (physics.class-ph), Metamaterial, Physics - Applied Physics, 021001 nanoscience & nanotechnology, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Interferometry, Amplitude, Transmission (telecommunications), Reflection (physics), lcsh:Q, 0210 nano-technology, business
Abstract

Utilizing the effect of losses, we show that symmetric 3-port devices exhibit coherent perfect absorption of waves and we provide the corresponding conditions on the reflection and transmission coefficients. Infinite combinations of asymmetric inputs with different amplitudes and phase at each port as well as a completely symmetric input, are found to be perfectly absorbed. To illustrate the above we study an acoustic 3-port network operating in a subwavelength frequency both theoretically and experimentally. In addition we show how the output from a 3-port network is altered, when conditions of perfect absorption are met but the input waves phase and amplitude vary. In that regard, we propose optimized structures which feature both perfect absorption and perfect transmission at the same frequency by tuning the amplitudes and phases of the input waves.

Published
2018

111. Revealing misleading schemes through operator activity analysis: A factory case study

Author

Franck Mars, Camilo Charron, Marie Hoarau, Laboratoire des Sciences du Numérique de Nantes (LS2N), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Région Pays de la Loire (projet ARTUR), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Nantes (ECN)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
Scheme (programming language), Computer science, Process (engineering), [SHS.PSY]Humanities and Social Sciences/Psychology, aeronautical factory, Human Factors and Ergonomics, Machine learning, computer.software_genre, 050105 experimental psychology, Industrial and Manufacturing Engineering, Operator (computer programming), activity analysis, Ecological interface design, 0501 psychology and cognitive sciences, 050107 human factors, Abstraction (linguistics), computer.programming_language, Hierarchy, business.industry, 05 social sciences, Representation (systemics), misleading scheme, Factory (object-oriented programming), Artificial intelligence, business, computer
Abstract

International audience; This article presents an activity analysis carried out in an aeronautical factory. The representation of the real process and the operators’ representations were identified. The representation of the real process was elaborated using an abstraction hierarchy, as described by the ecological interface design framework. The operators’ representations were extracted through interviews and observations and described in terms of schemes. The analysis revealed that operators in the studied factory used misleading schemes (i.e., false representations) to organize their activities, resultingin poor performance.We conclude by offering possible remedies, including training aimed at inhibiting the misleading scheme and a simulation tool to convey a more accurate representation.

Published
2018

112. High-throughput authentication of edible oils with benchtop Ultrafast 2D NMR

Author

Benoît Charrier, Boris Gouilleux, Gérald S. Remaud, Jérémy Marchand, Patrick Giraudeau, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), and Région Pays de la Loire (Grant RésoNantes)

Subjects
Hazelnut oil, Magnetic Resonance Spectroscopy, Rapeseed, Food industry, Analytical chemistry, Food Contamination, 01 natural sciences, Analytical Chemistry, Corylus, Plant Oils, Sunflower Oil, [CHIM]Chemical Sciences, Olive Oil, Chromatography, 010405 organic chemistry, Chemistry, business.industry, 010401 analytical chemistry, General Medicine, Nuclear magnetic resonance spectroscopy, 0104 chemical sciences, Rapeseed Oil, Corn Oil, business, Two-dimensional nuclear magnetic resonance spectroscopy, Sesame Oil, Food Science, Olive oil
Abstract

International audience; We report the use of an Ultrafast 2D NMR approach applied on a benchtop NMR system (43 MHz) for the authentication of edible oils. Our results demonstrate that a profiling strategy based on fast 2D NMR spectra recorded in 2.4 min is more efficient than the standard 1D experiments to classify oils from different botanical origins, since 1D spectra on the same samples suffer from strong peak overlaps. Six edible oils with different botanical origins (olive, hazelnut, sesame, rapeseed, corn and sunflower) have been clearly discriminated by PCA analysis. Furthermore, we show how this approach combined with a PLS model can detect adulteration processes such as the addition of hazelnut oil into olive oil, a common fraud in food industry.

Published
2018

113. Energy Harvesting using a Lead Zirconate Titanate (PZT) Thin Film on a Polymer Substrate

Author

Benoit Guiffard, Thibault Dufay, Raynald Seveno, Jean-Christophe Thomas, Institut d'Électronique et des Technologies du numéRique (IETR), Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), 2014 07965, Région Pays de la Loire, Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)

Subjects
energy conversion, Materials science, Composite number, 02 engineering and technology, chemical transfer, Lead zirconate titanate, 7. Clean energy, 01 natural sciences, [SPI]Engineering Sciences [physics], chemistry.chemical_compound, 0103 physical sciences, Polymer substrate, Electrical measurements, Composite material, Thin film, polymers, FOIL method, PZT thin films, interdigitated electrodes, 010302 applied physics, 021001 nanoscience & nanotechnology, Ferroelectricity, Isotropic etching, General Energy, chemistry, 0210 nano-technology
Abstract

International audience; A composite structure with an highly flexible polymer substrate and a thin film of lead zirconate titanate, Pb(Zr,Ti)O3 (PZT), is realized using an all‐chemical process. The fabrication of the structure comprises three steps: first, PZT is deposited on an aluminum thin foil, then the PZT thin film is bonded to a polymer, and, finally, aluminum foil is removed by selective chemical etching. Structural characterization techniques are used to ensure the quality of the PZT/polymer composite structure. Electrical measurements are also performed to confirm the ferroelectric characteristics of the composite. Finally, energy harvesting measurements are realized with interdigitated electrodes structure. A maximal energy density of 20 μJ cm−2 is obtained with manual mechanical excitation and an output voltage up to 35 V under free oscillations conditions in bending mode. This demonstrates that the recently developed PZT/polymer thin films are very promising for low‐frequency vibrating energy‐harvesting applications.

Published
2018

114. Duality and General Equilibrium Theory Under Knightian Uncertainty

Author

Laurent Denis, Patrick Beissner, University of Canberra, Laboratoire Manceau de Mathématiques, Laboratoire Manceau de Mathématiques (LMM), Le Mans Université (UM)-Le Mans Université (UM), Projet PANORisk, région Pays de la Loire, and ANR-15-CE05-0024,CAESARS,Contrôle et simulation des systèmes électriques, interaction et robustesse(2015)

Subjects
general equilibrium under uncertainty, Numerical Analysis, dual space, 050208 finance, General equilibrium theory, Dual space, Applied Mathematics, 05 social sciences, Duality (mathematics), volatility uncertainty, Asset pricing, Space (mathematics), [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], space of contingent claims, 0502 economics and business, Capital asset pricing model, Standard probability space, mutually singular probability measures, Commodity (Marxism), Mathematical economics, Finance, 050205 econometrics, Knightian uncertainty, Mathematics
Abstract

Any dynamic or stochastic notion of a general equilibrium relies on the underlying commodity space. Under sole risk and without multiple–prior uncertainty the usual choice is a Lebesgue space from standard measure theory. In the case of volatility uncertainty it turns out that such a type of function space is no longer appropriate. For this reason we introduce and discuss a new natural commodity space, which can be constructed in three independent and equivalent ways. Each approach departs from one possible way to construct Lebesgue spaces. Moreover, we give a complete representation of the resulting topological dual space. This extends the classic Riesz representation in a natural way. Elements therein are the candidates for a linear equilibrium price system. This representation result has direct implications for the microeconomic foundation of finance under Knightian uncertainty.

Published
2018

115. Pharmacology of Recombinant Adeno-associated Virus Production

Author

Magalie Penaud-Budloo, Nathalie Clement, Achille François, Eduard Ayuso, JAULIN, Nicolas, Démonstrateurs - Consortium préindustriel des vecteurs de thérapie génique - - PGT2010 - ANR-10-DPBS-0001 - DPBS - VALID, Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Powell Gene Therapy [Gainesville, FL, USA], Department of Pediatrics [Gainesville, FL, USA], University of Florida [Gainesville] (UF)-University of Florida [Gainesville] (UF), Financial support to E.A.’s laboratory was provided by INSERM, University of Nantes, CHU of Nantes, Fondation d’Entreprises pour la Thérapie Génique en Pays de la Loire, and Région Pays de la Loire and Pre-industrial gene therapy consortium (Agence Nationale de la Recherche-investissements d’avenir, grant number 10-DPBS-0001)., ANR-10-DPBS-0001,PGT,Consortium préindustriel des vecteurs de thérapie génique(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
0301 basic medicine, lcsh:QH426-470, viral vectors, [SDV]Life Sciences [q-bio], Genetic enhancement, viruses, quality controls, Biology, medicine.disease_cause, impurities, Article, law.invention, Viral vector, 03 medical and health sciences, Plasmid, law, Genetics, medicine, lcsh:QH573-671, Molecular Biology, Adeno-associated virus, lcsh:Cytology, AAV, Virology, gene therapy, [SDV] Life Sciences [q-bio], lcsh:Genetics, manufacturing, 030104 developmental biology, Herpes simplex virus, Helper virus, Recombinant DNA, Molecular Medicine, Homologous recombination
Abstract

International audience; Recombinant adeno-associated viral (rAAV) vectors have been used in more than 150 clinical trials with a good safety profile and significant clinical benefit in many genetic diseases. In addition, due to their ability to infect non-dividing and dividing cells and to serve as efficient substrate for homologous recombination, rAAVs are being used as a tool for gene-editing approaches. However, manufacturing of these vectors at high quantities and fulfilling current good manufacturing practices (GMP) is still a challenge, and several technological platforms are competing for this niche. Herein, we will describe the most commonly used upstream methods to produce rAAVs, paying particular attention to the starting materials (input) used in each platform and which related impurities can be expected in final products (output). The most commonly found impurities in rAAV stocks include defective particles (i.e., AAV capsids that do contain the therapeutic gene or are not infectious), residual proteins from host cells and helper viruses (adenovirus, herpes simplex virus, or baculoviruses), and illegitimate DNA from plasmids, cells, or helper viruses that may be encapsidated into rAAV particles. Given the role that impurities may play in immunotoxicity, this article reviews the impurities inherently associated with each manufacturing platform.

Published
2018

116. Intestinal multicellular organoids to study colorectal cancer

Author

Veerle Melotte, Maria M. Alves, Maxime M. Mahe, Robert M.W. Hofstra, Musa Idris, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Erasmus University Medical Center [Rotterdam] (Erasmus MC), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Cincinnati Children's Hospital Medical Center, 'New Team' grant (BOGUS to MM) from the Bioregate Regenerative Medicine Cluster, University of Nantes and Région Pays de la Loire, ANR-17-CE14-0021,SyNEDI,Rôle du Système Nerveux Entérique sur le Développement Intestinal chez l'Homme.(2017), MAHE, Maxime, and Rôle du Système Nerveux Entérique sur le Développement Intestinal chez l'Homme. - - SyNEDI2017 - ANR-17-CE14-0021 - AAPG2017 - VALID

Subjects
HUMAN COLON, Cancer Research, Colorectal cancer, EPITHELIUM, DIVERSITY, [SDV.CAN]Life Sciences [q-bio]/Cancer, MICROENVIRONMENT, DISEASE, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Genetics, Organoid, Humans, Medicine, Induced pluripotent stem cell, neoplasms, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, business.industry, Modeling, PLATFORM, Treatment options, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, Intestines, Organoids, Multicellular organism, DIFFERENTIATION, Oncology, 030220 oncology & carcinogenesis, Cancer research, Colorectal Neoplasms, business, PLURIPOTENT STEM-CELLS
Abstract

International audience; Modeling colorectal cancer (CRC) using organoids has burgeoned in the last decade, providing enhanced in vitro models to study the development and possible treatment options for this type of cancer. In this review, we describe both normal and CRC intestinal organoid models and their utility in the cancer research field. Besides highlighting studies that develop epithelial CRC organoid models, i.e. organoids without tumor microenvironment (TME) cellular components, we emphasize on the need for TME in CRC modeling, to help reduce translational disparities in this area. Also, we discuss the utilization of CRC organoids derived from pluripotent stem cells, as well as their potential to be used in cancer research. Finally, limitations and challenges in the current CRC organoids field, are discussed.

Published
2021

117. Nanomedicine as a potent strategy in melanoma tumor microenvironment

Author

Vincent Pautu, Catherine Passirani, Elise Lepeltier, Daniela Leonetti, Nicolas Clere, Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), The authors would like to thanks the Région Pays de la Loire and the Erasmus Mundus program for the financing of the Ph D programm of Vincent Pautu., Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Endothelium radiobiology and targeting (CRCINA - Département ONCO - Equipe 14), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
0301 basic medicine, Skin Neoplasms, medicine.drug_class, [SDV.CAN]Life Sciences [q-bio]/Cancer, Drug resistance, Monoclonal antibody, Metastasis, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, Humans, Melanoma, Pharmacology, Targeting, Tumor microenvironment, Nanotheranostics, business.industry, Antibodies, Monoclonal, medicine.disease, 3. Good health, Nanomedicine, 030104 developmental biology, Formulation, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Nanotherapies, Drug delivery, Immunology, Cancer research, Nanoparticles, Skin cancer, business
Abstract

International audience; Melanoma originated from melanocytes is the most aggressive type of skin cancer. Despite considerable progresses in clinical treatment with the discovery of BRAF or MEK inhibitors and monoclonal antibodies, the durability of response to treatment is often limited to the development of acquired resistance and systemic toxicity. The limited success of conventional treatment highlights the importance of understanding the role of melanoma tumor microenvironment in tumor developement and drug resistance. Nanoparticles represent a promising strategy for the development of new cancer treatments able to improve the bioavailability of drugs and increase their penetration by targeting specifically tumors cells and/or tumor environment. In this review, we will discuss the main influence of tumor microenvironment in melanoma growth and treatment outcome. Furthermore, third generation loaded nanotechnologies represent an exciting tool for detection, treatment, and escape from possible mechanism of resistance mediated by tumor microenvironment, and will be highlighted in this review.

Published
2017

118. Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial

Author

Vandamme, Céline, Adjali, Oumeya, Mingozzi, Federico, Department of Clinical Microbiology [Kuopio, Finland], University of Eastern Finland- Institute of Clinical Medicine [Kuopio, Finland], Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), F.M.’s work was supported by Genethon. It was also supported by the European Union’s research and innovation program under Grant Agreement No. 667751 (MYOCURE to F.M.), the European Research Council Consolidator Grant under Grant Agreement No. 617432 (MoMAAV to F.M.), and the R-Rare2 consortium grant SMART-HaemoCare. O.A. and C.V. were supported by the Inserm, the French Ministry of Research, the F.R.M. (Fondation pour la Recherche Me´dicale), the University Hospital of Nantes, the Fondation pour la Thérapie Génique en Pays de Loire, the AFM-Téléthon (Association Française contre les Myopathies), the Région Pays de la Loire (IMBIO-DC consortium), and the IHU-CESTI, which is supported by the French National Research Agency (ANR) via the ‘‘Investment Into The Future’’ program ANR-10-IBHU-005., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), European Project: 667751,H2020,H2020-PHC-2015-two-stage,MYOCURE(2016), European Project: 617432,EC:FP7:ERC,ERC-2013-CoG,MOMAAV(2014), École Pratique des Hautes Études (EPHE), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), JAULIN, Nicolas, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Development of an innovative gene therapy platform to cure rare hereditary muscle disorders - MYOCURE - - H20202016-01-01 - 2019-12-31 - 667751 - VALID, and Molecular signatures and Modulation of immunity to Adeno-Associated Virus vectors - MOMAAV - - EC:FP7:ERC2014-07-01 - 2019-06-30 - 617432 - VALID

Subjects
Clinical Trials as Topic, Immunity, Cellular, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], viruses, Genetic Vectors, T cells, Genetic Therapy, CD8-Positive T-Lymphocytes, Dependovirus, gene therapy, immune responses, AAV vectors, [SDV] Life Sciences [q-bio], Humans, Capsid Proteins, antibody responses, Review Articles, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Over the past decade, vectors derived from adeno-associated virus (AAV) have established themselves as apowerful tool for in vivo gene transfer, allowing long-lasting and safe transgene expression in a variety of humantissues. Nevertheless, clinical trials demonstrated how B and T cell immune responses directed against the AAVcapsid, likely arising after natural infection with wild-type AAV, might potentially impact gene transfer safetyand efficacy in patients. Seroprevalence studies have evidenced that most individuals carry anti-AAV neutralizingantibodies that can inhibit recombinant AAV transduction of target cells following in vivo administration ofvector particles. Likewise, liver- and muscle-directed clinical trials have shown that capsid-reactive memoryCD8+T cells could be reactivated and expanded upon presentation of capsid-derived antigens on transduced cells,potentially leading to loss of transgene expression and immune-mediated toxicities. In celebration of the 25thanniversary of the European Society of Gene and Cell Therapy, this review article summarizes progress madeduring the past decade in understanding and modulating AAV vector immunogenicity. While the knowledgegenerated has contributed to yield impressive clinical results, several important questions remain unanswered,making the study of immune responses to AAV a priority for the field of in vivo transfer.

Published
2017

119. Analyse des vermoulures pour la détermination de quelques espèces d’insectes xylophages de la famille des Ptinidae (Coleoptera)

Author

Fabien Fohrer, Magali Toriti, Aline Durand, Centre Interdisciplinaire de Conservation et Restauration du Patrimoine (CICRP), Ministère de la Culture et de la Communication (MCC), Le Mans Université (UM), Centre de Recherche en Archéologie, Archéosciences, Histoire (CReAAH), Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), Université de Nantes (UN)-Université de Nantes (UN)-Ministère de la Culture (MC), Contrat doctoral région Pays de la Loire Projet OSUR Observatoire des Sciences de l'Univers de Rennes, Nantes Université (NU)-Ministère de la Culture (MC)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), and Université de Rennes (UNIV-RENNES)-Le Mans Université (UM)

Subjects
xylophage, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, vermoulure, Xylophagous, fecal pellets, pest management, Forestry, Biology, insecte, clé de détermination, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, xylophageous, déjection, identification, insect, Ptinidae
Abstract

Analysis of larval frass for identification of wood boring insects of the family Ptinidae (Coleoptera). Among xylophagous insects of the family Ptinidae, the common furniture beetle Anobium punctatum (Degeer, 1774), with a worldwide distribution, is the most commonly found species in heritage sites and places. Besides, other species like the furniture beetle Oligomerus ptilinoides (Wollaston, 1854) and the library beetle Nicobium castaneum (Olivier, 1790), are often found in the same places. They all cause extensive damage to various objects, and the traces they leave (flight holes, size and shape of their excrement, presence or absence of pupae, etc.) differ among species. This study presents a comparative, morphological and statistical approach for studying the clues left by these three species so as to differentiate and identify them in the absence of larvae or imagoes., Parmi les Insectes xylophages de la famille des Ptinidae, la petite vrillette Anobium punctatum (Degeer, 1774), espèce cosmopolite, est la plus fréquemment rencontrée dans les espaces et lieux patrimoniaux. Par ailleurs, d’autres espèces comme la vrillette brune Oligomerus ptilinoides (Wollaston, 1854) et la vrillette des bibliothèques Nicobium castaneum (Olivier, 1790), se rencontrent souvent dans ces mêmes lieux. Toutes occasionnent de nombreux dégâts sur divers objets patrimoniaux et les traces qu’elles génèrent (trous d‘émergence, taille et forme des déjections, présence ou non de coque de nymphose, etc.) ne sont pas identiques d’une espèce à l’autre. Pour les trois espèces considérées, cette étude présente une approche comparative, morphologique et statistique, de ces traces d’activité permettant ainsi leur différenciation et leur identification en l’absence de larves ou d’imagos., Fohrer Fabien, Toriti Magali, Durand Aline. Analyse des vermoulures pour la détermination de quelques espèces d’insectes xylophages de la famille des Ptinidae (Coleoptera). In: Bulletin de la Société entomologique de France, volume 122 (2),2017. pp. 133-142.

Published
2017

120. Table-ronde 'Un territoire en perspective'

Author

Vincent, Johan, Temps, Mondes, Sociétés (TEMOS), Le Mans Université (UM)-Université d'Angers (UA)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS), Espaces et Sociétés (ESO), Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université d'Angers (UA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM), Région Pays-de-la-Loire, Le Mans Université (UM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-AGROCAMPUS OUEST-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
[SHS.ARCHI]Humanities and Social Sciences/Architecture, space management, [SHS.GEO]Humanities and Social Sciences/Geography, [SHS.HIST]Humanities and Social Sciences/History, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2019

121. Scènes locales, clusters culturels et quartiers créatifs

Author

Emin, Sandrine, Schieb-Bienfait, Nathalie, Université d'Angers (UA), Groupe de Recherche Angevin en Economie et Management (GRANEM), Université d'Angers (UA)-AGROCAMPUS OUEST-Institut National de l'Horticulture et du Paysage, Région Pays de la Loire, Université d'Angers (UA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de l'Horticulture et du Paysage

Subjects
Clusters, ICC, [SHS.GESTION]Humanities and Social Sciences/Business administration, scènes locales, villes créatives, [SHS]Humanities and Social Sciences
Abstract

International audience; Cet ouvrage s’articule autour de contributions de chercheurs en sciences sociales, qui proposent d’approfondir la connaissance des clusters culturels et des scènes culturelles locales. La première partie fait le point sur les acceptions, méthodes et approches mobilisées selon les différentes disciplines dans l’analyse des clusters culturels et des scènes locales, et permet de mieux comprendre les interpénétrations entre les deux concepts. L’ouvrage traite également des démarches pour accompagner les choix de spécialisation dans la culture et penser l’action publique territoriale. A partir de l’étude d’exemples concrets tant en France (Nantes, Lille) qu’à l’étranger (Québec, Barcelone, Istanbul, Gênes), la deuxième partie est consacrée à la question de la gouvernance des clusters et à celle de leur instrumentation politique. La troisième et dernière partie examine les enjeux du regroupement d’acteurs culturels et créatifs sur un territoire localisé, avec une analyse des mécanismes par lesquels ils sont producteurs de dynamiques économiques, culturelles, sociales, territoriales. En privilégiant une perspective comparative, l’ensemble de l’ouvrage invite à interroger les échelles territoriales et la temporalité des phénomènes étudiés.

Published
2019

122. Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors

Author

Autin, Pierre, Blanquart, Christophe, Fradin, Delphine, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Our research was funded by grant from Ligue contre le Cancer, comités 22, 29, 35, 44, 56 and from Cancéropole Grand Ouest—AO Structurant—ExomiR. P.A. was supported by a grant from Région Pays de la Loire—Episavmen., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, HDAC inhibitors, cancer, exosome, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

International audience; Over recent decades, it has become clear that epigenetic abnormalities are involved in the hallmarks of cancer. Histone modifications, such as acetylation, play a crucial role in cancer development and progression, by regulating gene expression, such as for oncogenes or tumor suppressor genes. Therefore, histone deacetylase inhibitors (HDACi) have recently shown efficacy against both hematological and solid cancers. Designed to target histone deacetylases (HDAC), these drugs can modify the expression pattern of numerous genes including those coding for micro-RNAs (miRNA). miRNAs are small non-coding RNAs that regulate gene expression by targeting messenger RNA. Current research has found that miRNAs from a tumor can be investigated in the tumor itself, as well as in patient body fluids. In this review, we summarized current knowledge about HDAC and HDACi in several cancers, and described their impact on miRNA expression. We discuss briefly how circulating miRNAs may be used as biomarkers of HDACi response and used to investigate response to treatment.

Published
2019

123. Investigation of Phospholipase Cγ1 Interaction with SLP76 Using Molecular Modeling Methods for Identifying Novel Inhibitors

Author

Neha Tripathi, Mickael Jean, Patrick Legembre, Adèle D. Laurent, Iyanar Vetrivel, Stéphane Téletchéa, Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), CRLCC Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), PLBIO-2018, Institut National Contre le Cancer (INCa), Mim-Breg, Région Pays de la Loire, CE15-0027, Agence Nationale de la Recherche, 2017-2019 (PL), Fondation ARC pour la Recherche sur le Cancer, Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-17-CE15-0027,FASILE,Impact du CD95L, dans la dysfonction des lymphocytes T exprimant l'IL-17 au cours du lupus(2017), and Jonchère, Laurent

Subjects
Molecular model, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], pharmacophore mapping, Computational biology, Phospholipase, Phospholipase C gamma, Article, Catalysis, SH3 domain, lcsh:Chemistry, Inorganic Chemistry, phospholipase C gamma 1, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, medicine, Humans, Enzyme Inhibitors, Physical and Theoretical Chemistry, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, 030304 developmental biology, 0303 health sciences, Virtual screening, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Drug discovery, Chemistry, Organic Chemistry, General Medicine, molecular docking, virtual screening, SLP76, molecular dynamics, 3. Good health, Computer Science Applications, Molecular Docking Simulation, lcsh:Biology (General), lcsh:QD1-999, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ritonavir, Pharmacophore, Peptides, Protein Binding, medicine.drug
Abstract

The enzyme phospholipase C gamma 1 (PLC&gamma, 1) has been identified as a potential drug target of interest for various pathological conditions such as immune disorders, systemic lupus erythematosus, and cancers. Targeting its SH3 domain has been recognized as an efficient pharmacological approach for drug discovery against PLC&gamma, 1. Therefore, for the first time, a combination of various biophysical methods has been employed to shed light on the atomistic interactions between PLC&gamma, 1 and its known binding partners. Indeed, molecular modeling of PLC&gamma, 1 with SLP76 peptide and with previously reported inhibitors (ritonavir, anethole, daunorubicin, diflunisal, and rosiglitazone) facilitated the identification of the common critical residues (Gln805, Arg806, Asp808, Glu809, Asp825, Gly827, and Trp828) as well as the quantification of their interaction through binding energies calculations. These features are in agreement with previous experimental data. Such an in depth biophysical analysis of each complex provides an opportunity to identify new inhibitors through pharmacophore mapping, molecular docking and MD simulations. From such a systematic procedure, a total of seven compounds emerged as promising inhibitors, all characterized by a strong binding with PLC&gamma, 1 and a comparable or higher binding affinity to ritonavir (∆Gbind &lt, &minus, 25 kcal/mol), one of the most potent inhibitor reported till now.

Published
2019

124. Immunophenotype of a Rat Model of Duchenne's Disease and Demonstration of Improved Muscle Strength After Anti-CD45RC Antibody Treatment

Author

Laure-Hélène Ouisse, Séverine Remy, Aude Lafoux, Thibaut Larcher, Laurent Tesson, Vanessa Chenouard, Carole Guillonneau, Lucas Brusselle, Nadège Vimond, Karl Rouger, Yann Péréon, Alexis Chenouard, Christèle Gras-Le Guen, Cécile Braudeau, Régis Josien, Corinne Huchet, Ignacio Anegon, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de Biotechnologie, Biocatalyse et Biorégulation (U3B), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA), Atlantic Gene Therapies, Clinique Médicale et Service d'Urgences Pédiatriques, Hôpital Mère-Enfant, Centre hospitalier universitaire de Nantes (CHU Nantes), Thérapie génique translationnelle pour les maladies neuromusculaires et de la rétine, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biogenouest and the TEFOR, Nantes Métropole and Région Pays de la Loire, Anegon, Ignacio, Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Le Bihan, Sylvie, and Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
0301 basic medicine, T-Lymphocytes, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immune tolerance, Treg, tolerance, muscle injury, dystrophin, immunosuppression, knockout rats, nucleases, 0302 clinical medicine, Immunophenotyping, TALEN, Immunology and Allergy, Medicine, Muscular dystrophy, Original Research, biology, Antibodies, Monoclonal, Immunosuppression, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Prednisolone, Cytokines, medicine.symptom, Dystrophin, medicine.drug, lcsh:Immunologic diseases. Allergy, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Immunology, Inflammation, 03 medical and health sciences, Internal medicine, Animals, Muscle Strength, Muscle, Skeletal, business.industry, Macrophages, Skeletal muscle, medicine.disease, Rats, Muscular Dystrophy, Duchenne, Disease Models, Animal, 030104 developmental biology, Endocrinology, biology.protein, Leukocyte Common Antigens, lcsh:RC581-607, business, Spleen, 030215 immunology
Abstract

International audience; Corticosteroids (CS) are standard therapy for the treatment of Duchenne's muscular dystrophy (DMD). Even though they decrease inflammation, they have limited efficacy and are associated with significant side effects. There is therefore the need for new protolerogenic treatments to replace CS. Dystrophin-deficient rats (Dmd mdx ) closely resemble the pathological phenotype of DMD patients. We performed the first Immunophenotyping of Dmd mdx rats and showed leukocyte infiltration in skeletal and cardiac muscles, which consisted mostly of macrophages and T cells including CD45RChigh T cells. Muscles of DMD patients also contain elevated CD45RChigh T cells. We treated Dmd mdx rats with an anti-CD45RC MAb used in previous studies to deplete CD45RChigh T cells and induce immune tolerance in models of organ transplantation. Treatment of young Dmd mdx rats with anti-CD45RC MAb corrected skeletal muscle strength and was associated with depletion of CD45RChigh T cells with no side effects. Treatment of young Dmd mdx rats with prednisolone resulted in increase in skeletal muscle strength but also severe growth retardation. In conclusion, anti-CD45RC MAb treatment has potential in the treatment of DMD and might eventually result in reduction or elimination of CS use.

Published
2019

125. Early Identification of Chronic Lung Allograft Dysfunction: The Need of Biomarkers

Author

Adrien Tissot, Richard Danger, Johanna Claustre, Antoine Magnan, Sophie Brouard, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pneumologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de transplantation urologie-néphrologie (ITUN), Service Hospitalier Universitaire Pneumologie-Physiologie [CHU Grenoble Alpes] (Pôle Thorax et Vaisseaux), Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), The IHU-Cesti project is also supported by Nantes Métropole and Région Pays de la Loire. JC was supported by Fondation du souffle and Fonds Agir pour les maladies chroniques grants., Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Unité de recherche de l'institut du thorax (ITX-lab), and Le Bihan, Sylvie

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, Immunology, Review, 03 medical and health sciences, 0302 clinical medicine, blood, medicine, lung transplantation, Immunology and Allergy, Lung transplantation, Animals, Humans, Routine clinical practice, Respiratory function, BOS, Intensive care medicine, Lung, Lung function, chronic lung allograft dysfunction, Immunity, Cellular, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, bronchoalveolar lavage fluid, business.industry, High mortality, Allografts, 3. Good health, Immunity, Humoral, 030104 developmental biology, medicine.anatomical_structure, Biomarker (medicine), biomarker, lcsh:RC581-607, business, Airway, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, 030215 immunology, RAS
Abstract

International audience; A growing number of patients with end-stage lung disease have benefited from lung transplantation (LT). Improvements in organ procurement, surgical techniques and intensive care management have greatly increased short-term graft survival. However, long-term outcomes remain limited, mainly due to the onset of chronic lung allograft dysfunction (CLAD), whose diagnosis is based on permanent loss of lung function after the development of irreversible lung lesions. CLAD is associated with high mortality and morbidity, and its exact physiopathology is still only partially understood. Many researchers and clinicians have searched for CLAD biomarkers to improve diagnosis, to refine the phenotypes associated with differential prognosis and to identify early biological processes that lead to CLAD to enable an early intervention that could modify the inevitable degradation of respiratory function. Donor-specific antibodies are currently the only biomarkers used in routine clinical practice, and their significance for accurately predicting CLAD is still debated. We describe here significant studies that have highlighted potential candidates for reliable and non-invasive biomarkers of CLAD in the fields of imaging and functional monitoring, humoral immunity, cell-mediated immunity, allograft injury, airway remodeling and gene expression. Such biomarkers would improve CLAD prediction and allow differential LT management regarding CLAD risk.

Published
2019

126. CXCR5+PD1+ICOS+ circulating T follicular helpers are associated with de novo donor-specific antibodies after renal transplantation

Author

Danger, Richard, Chesneau, Mélanie, Delbos, Florent, Le Bot, Sabine, Kerleau, Clarisse, Chenouard, Alexis, Ville, Simon, Degauque, Nicolas, Conchon, Sophie, Cesbron, Anne, Giral, Magali, Brouard, Sophie, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Etablissement Français du Sang [Nantes], CIC biothérapies CBT 0503 [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM), DIVAT consortium, Réseau CENTAURE [CHU Nantes] (Fondation, Centre d’Investigation Clinique en Biothérapie), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*), This work was supported by the CENTAURE foundation (www.fondation-centaure.org), which supports a French transplantation research network, the IHU-Cesti project, the DHU Oncogreffe, and the LabEX IGO thanks to French government financial support managed by the National Research Agency via the Investment into the Future program (ANR-10-IBHU-005 and ANR-11- LABX-0016-01). The IHU-Cesti project was also supported by Nantes Métropole and Région Pays de la Loire. This work was performed in the context of the ANR project BIKET (ANR-17-CE17-0008). RD was supported by a Marie Skłodowska-Curie fellowship (IF-EF) from the European Union’s Horizon 2020 research and innovation programme under the Grant Agreement No. 706296., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-17-CE17-0008,Biket,Cellules B GZMB+, un facteur clé de l'immunité chez l'homme?(2017), European Project: 706296,H2020,H2020-MSCA-IF-2015,DISTRICT(2017), ANR-10-IBHU-0005,CESTI (TSI-IHU),CESTI (TSI-IHU)(2010), Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Cellules B GZMB+, un facteur clé de l'immunité chez l'homme? - - Biket2017 - ANR-17-CE17-0008 - AAPG2017 - VALID, and DECIPHERING THE ROLE OF TRIB1 IN REGULATORY T CELLS - DISTRICT - - H20202017-07-01 - 2019-06-30 - 706296 - VALID

Subjects
[SDV] Life Sciences [q-bio], donor-specific antibodi es, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, circulating T follicular helper lymphocytes, [SDV]Life Sciences [q-bio], Tfh, renal transplantation, DSA, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Donor-specific anti-HLA antibodies (DSAs) are a major risk factor associated with renal allograft outcomes. As a trigger of B cell antibody production, T follicular helper cells (Tfhs) promote DSA appearance. Herein, we evaluated whether circulating Tfhs (cTfhs) are associated with the genesis of antibody-mediated rejection. We measured cTfh levels on the day of transplantation and 1 year after transplantation in blood from a prospective cohort of 237 renal transplantation patients without DSA during the first year post-transplantation. Total cTfhs were characterized as CD4+CD45RA-CXCR5+, and the three following subsets of activated cTfh were analyzed: CXCR5+PD1+, CXCR5+PD1+ICOS+, an CXCR5+PD1+CXCR3-. Immunizing events (previous blood transfusion and/or pregnancy) and the presence of class II anti-HLA antibodies were associated with increased frequencies of activated CXCR5+PD1+, CXCR5+PD1+ICOS+, and CXCR5+PD1+CXCR3- cTfh subsets. In addition, ATG-depleting induction and calcineurin inhibitor treatments were associated with a relative increase of activated cTfh subsets frequencies at 1 year post-transplantation. In multivariate survival analysis, we reported that a decrease in activated CXCR5+PD1+ICOS+ at 1 year after transplantation in the blood of DSA-free patients was significantly associated with the risk of developing de novo DSA after the first year (p = 0.018, HR = 0.39), independently of HLA mismatches (p = 0.003, HR = 3.79). These results highlight the importance of monitoring activated Tfhs in patients early after transplantation and show that current treatments cannot provide early, efficient prevention of Tfh activation and migration. These findings indicate the need to develop innovative treatments to specifically target Tfhs to prevent DSA appearance in renal transplantation.

Published
2019

127. Lipidic Aminoglycoside Derivatives: A New Class of Immunomodulators Inducing a Potent Innate Immune Stimulation

Author

COLOMBANI, T., HAUDEBOURG, T., DECOSSAS, M., LAMBERT, O., DA SILVA, G. A., ALTARE, F., PITARD, B., Host-Pathogen Interactions in the Regulation of Immune Responses (CRCINA-ÉQUIPE 5), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), This work was supported by special grants from BPI France financement (Paris, France) for EMERIT project. T.C. was supported by funds from IHU-CESTI (French government financial support managed by the National Research Agency 'Investment into The Future' program ANR-10-IBHU-005, cosupported by Région Pays de la Loire and Nantes Métropole)., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Bernardo, Elizabeth, and Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Full Paper, [SDV]Life Sciences [q-bio], [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Full Papers, cationic lipids, phosphatidylinositol phospholipase C (PLC), [SDV] Life Sciences [q-bio], lipoaminoglycosides, adjuvants, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, immunotherapy, lcsh:Science
Abstract

International audience; Development of simple and fully characterized immunomodulatory molecules is an active area of research to enhance current immunotherapies. Monophosphoryl lipid A (MPL), a nontoxic lipidic derivative from bacteria, is the first and currently only adjuvant approved in humans. However, its capacity to induce a potent response against weak immunogenic tumoral-associated antigens remains limited. Herein, a new generation of lipidic immunomodulators to conduct a structure-activity relationship study to determine the minimal structural elements conferring immunomodulatory properties is introduced. Two lead molecules characterized by a short succinyl linker between two oleyl chains and a polar headgroup consisting of either naturally occurring tobramycin (DOST) or kanamycin (DOSK) are identified. These two lipoaminoglycosides self-assemble in very small vesicles. In a wide variety of cells including 3D human cell culture, DOST and DOSK induce the upregulation of proinflammatory cytokines and interferon-inducible proteins in a dose and time-dependent manner via a caveolae-dependent proinflammatory mechanism and phosphatidylinositol phospholipase C activation. Furthermore, after intratumoral administration, these lipoaminoglycosides induce an efficient immune response leading to significant antitumor activity in a mouse breast cancer model. Altogether, these findings indicate that DOST and DOSK are two groundbreaking synthetic lipid immunostimulators that can be used as adjuvants to enhance current immunotherapeutic treatments.

Published
2019

128. La patrimonialisation du Cognac : un moyen de fédérer les acteurs du spiritueux et les acteurs du tourisme

Author

Piriou, Jérôme, Excelia Group | La Rochelle Business School, CEntre de REcherche en GEstion - EA 1722 (CEREGE), Institut d'Administration des Entreprises (IAE) - Poitiers (IAE Poitiers), Université de Poitiers-Université de Poitiers-Université de Poitiers-Université de La Rochelle (ULR), Espaces et Sociétés (ESO), Le Mans Université (UM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-AGROCAMPUS OUEST-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN), Université d'Angers, Ningbo University, CONstruction, Naissance, Evolution de Cluster Tourisme (CONNECT) : Innovation dans la gouvernance des destinations et le développement de clusters tourisme financé par la région Pays de la Loire (RFI Angers Tourism Lab), Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université d'Angers (UA)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM)

Subjects
[SHS.GEO]Humanities and Social Sciences/Geography
Abstract

International audience; Le Cognac, un spiritueux commercialisé à l’échelle internationale, est produit dans le sud-ouest de la France. Plusieurs acteurs agissent dans son élaboration et sa commercialisation notamment de puissantes maisons de négoces. Le tourisme n’est que peu présent dans le vignoble, il s’observe notamment par l’ouverture au grand public de circuits de visite au sein des maisons de négoces. Les maisons vendent leurs marques, leurs produits et s’appuient sur quelques références au terroir. Les acteurs du tourisme, quant à eux, assurent la promotion du territoire notamment par la renommée internationale des marques des maisons de négoces. Pourtant ces deux sphères professionnelles ne travaillent pas ensemble. La volonté de patrimonialisation, initiée par la municipalité, a pour objectif de valoriser une mémoire partagée. Mais la dimension internationale du commerce du Cognac semble en décalage avec une labélisation nationale du patrimoine de la ville. La mobilisation récente d’acteurs pour le portage d’une candidature à l’inscription par l’UNESCO au titre du patrimoine immatériel mondiale de l’humanité des savoir-faire du Cognac, répondrait davantage à la cible des acteurs du spiritueux. Nous exposerons dans quelles mesures les acteurs du tourisme et les acteurs du spiritueux peuvent se fédérer dans le cadre d’une patrimonialisation du Cognac.

Published
2019

129. Paracaspase MALT1 regulates glioma cell survival by controlling endo-lysosome homeostasis

Author

Nicolas Bidère, Tiphaine Douanne, Elizabeth Harford-Wright, An Thys, Ying Li, Clément Maghe, Carolina Alves Nicolau, Jean-Sebastien Frenel, Gwennan André-Grégoire, Julie Gavard, Kilian Trillet, Kathryn A Jacobs, Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Integrated Center for Oncology [Angers] (ICO), School of Life Sciences [Beijing, China], Tsinghua University [Beijing] (THU), This research was funded by Fondation pour la Recherche Medicale (Equipe labellisée DEQ20180339184), Fondation ARC contre le Cancer (JG PJA20171206146), Ligue nationale contre le cancer comités de Loire-Atlantique, Maine et Loire, Vendée, Ille-et-Vilaine (JG, NB), Région Pays de la Loire et Nantes Métropole under Connect Talent Grant (JG), and SIRIC ILIAD INCa-DGOS-Inserm_12558. KAJ received PhD fellowships from Nantes Métropole and Fondation ARC, TD received PhD fellowship from Nantes Métropole, GAG and AT hold postdoctoral fellowships from Fondation de France and Fondation ARC, respectively., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
Male, Apoptosis, Lymphocyte Activation, Mice, 0302 clinical medicine, glioma, Tumor Cells, Cultured, Homeostasis, 0303 health sciences, Gene knockdown, Mice, Inbred BALB C, Membranes & Traf- ficking, General Neuroscience, TOR Serine-Threonine Kinases, RNA-Binding Proteins, Articles, Paracaspase, Middle Aged, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Neoplastic Stem Cells, lysosome, mTOR, Female, Autophagy & Cell Death, Signal Transduction, Programmed cell death, protease Subject Categories Cancer, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endosomes, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glioma, Lysosome, medicine, Biomarkers, Tumor, Animals, Humans, Molecular Biology, PI3K/AKT/mTOR pathway, 030304 developmental biology, Aged, Cell Proliferation, General Immunology and Microbiology, MALT1, Autophagy, medicine.disease, Xenograft Model Antitumor Assays, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Proteolysis, Cancer research, Lysosomes, 030217 neurology & neurosurgery
Abstract

International audience; Glioblastoma is one of the most lethal forms of adult cancer with a median survival of around 15 months. A potential treatment strategy involves targeting glioblastoma stem-like cells (GSC), which constitute a cell autonomous reservoir of aberrant cells able to initiate, maintain, and repopulate the tumor mass. Here, we report that the expression of the paracaspase mucosa-associated lymphoid tissue l (MALT1), a protease previously linked to antigen receptor-mediated NF-jB activation and B-cell lymphoma survival, inversely correlates with patient probability of survival. The knockdown of MALT1 largely impaired the expansion of patient-derived stem-like cells in vitro, and this could be recapitulated with pharmacological inhibitors, in vitro and in vivo. Blocking MALT1 protease activity increases the endo-lysosome abundance, impairs autophagic flux, and culminates in lysosomal-mediated cell death, concomitantly with mTOR inactiva-tion and dispersion from endo-lysosomes. These findings place MALT1 as a new druggable target involved in glioblastoma and unveil ways to modulate the homeostasis of endo-lysosomes.

Published
2019

130. Exploration architecturale pour la tolérance aux fautes

Author

Nguyen, Thi-Tuyen, Charlier, Sandrine, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), CEA Tech en régions (CEA-TECH-Reg), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Projet HOLISTAR (Ressourcement CEA Tech en Région Pays de la Loire)., UNIVERSITE DE NANTES, Sébastien Pillement Professeur, Université de Nantes, Mathieu Thévenin Chercheur, CEA - Paris Saclay, Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), and Nantes Université (NU)-Université de Rennes 1 (UR1)

Subjects
[SPI.OTHER]Engineering Sciences [physics]/Other, Model Driven Engineering, tolérance aux fautes, [SPI.OTHER] Engineering Sciences [physics]/Other, Fault Tolerance, Ingénierie dirigée par les modèles, Design Space Exploration, MPSoC, [SPI.TRON] Engineering Sciences [physics]/Electronics, [SPI.TRON]Engineering Sciences [physics]/Electronics, exploration de l'espace de conception
Abstract

Reliability becomes a very important feature in the design process of an embedded system. Therefore, the development of fault tolerance strategies is also among the priorities in the early design phases of embedded systems. This thesis aims to establish a framework that allows finding the best platform solution for a given application in heterogeneous MultiProcessor System-on-Chip (MPSoC) systems. The found solution must be integrated the fault tolerance. A new platform meta-model integrated the fault tolerance is presented that roles an infrastructure to build models. The models are then inputs to a Design Space Exploration process. From the user specification, explored dimensions include hardware choice, task mapping, data mapping, and fault-tolerance-strategy choice. A new solution is generated and evaluated in terms of execution time, cost and, reliability level. Then, an optimization process will explore the best solution among the design space. A new tool with a graphical user interface allows to model and run the DSE process. It simplifies the process by interacting with the user through the graphical interface and automating the process of exploring design space. Evaluation of heterogeneous MPSoC platform under the impact of transient and permanent faults is a very important part of the DSE to help designers choose the appropriate strategy fault tolerance regarding a compromise with the requirements of the application. Finally, case-studies are invested. Experimental results showed that the DSE framework provides an effective exploration of large design space., La fiabilité devient une caractéristique très importante du processus de conception d’un système embarqué. Par conséquent, l'élaboration de stratégies de tolérance aux fautes fait également partie des priorités lors des premières phases de conception des systèmes embarqués. Cette thèse vise à établir un cadre permettant de trouver la meilleure solution de plate-forme pour une application donnée dans des systèmes multiprocesseurs hétérogènes. La solution trouvée doit être intégrée à la tolérance aux fautes. Un nouveau méta-modèle de plateforme intégrant la tolérance aux fautes est présenté qui joue le rôle d'infrastructure pour construire des modèles. Les modèles sont ensuite entrés dans un processus d'exploration de l'espace de conception. Dans la spécification utilisateur, les dimensions explorées incluent le choix du composant, le mapping des tâches, le mapping des données et le choix de la stratégie de tolérance aux fautes.Une nouvelle solution est générée et évaluée en matière de temps d'exécution, de coût et de niveau de fiabilité. Ensuite, un processus d'optimisation explore la meilleure solution parmi les espaces de conception. Un nouvel outil avec une interface utilisateur graphique permet de modéliser et d’exécuter le processus d’exploration. Il simplifie le processus en interagissant avec l'utilisateur via l'interface graphique et en automatisant le processus d'exploration de l'espace de conception. L'évaluation de la plate-forme MPSoC hétérogène sous l'impact de fautes transitoires et permanentes est une partie très importante de l’exploration pour aider des concepteurs à choisir la stratégie de tolérance aux fautes appropriée en ce qui concerne un compromis avec les exigences de l'application. Enfin, des études de cas sont investies. Les résultats expérimentaux ont montré que le cadre DSE fournit une exploration efficace de grands espaces de conception.

Published
2019

131. Doctrines et réalité(s) du bonheur

Author

Lemaire, Félicien, Blondel, Serge, Centre Jean Bodin : Recherche Juridique et Politique (CJB), Université d'Angers (UA), Groupe de Recherche Angevin en Economie et Management (GRANEM), Université d'Angers (UA)-AGROCAMPUS OUEST-Institut National de l'Horticulture et du Paysage, Programme BonDroit - Financement Région Pays de la Loire, Institut National de l'Horticulture et du Paysage-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université d'Angers (UA)

Subjects
dignité humaine, bien-être, épanouissement personnelle, Allemagne, États-Unis, qualité de vie, Bentham, impôts, organisations internationales, Adam Smith, bonheur, [SHS]Humanities and Social Sciences, Lumières, Constitutions, autonomie personnelle, Stuart Mill, France, santé, Travail, Révolutions française et américaine
Abstract

International audience; L’analyse du bonheur par le droit, tel est l’objet singulier de cet ouvrage. On y cherchera en vain l’affirmation, pour le moins prématurée, d’un droit au bonheur. Il faudrait pour cela globalement convaincre qu’on a réellement affaire dans les Etats à un droit autonome, en tant que tel strictement garanti. En dépit de certaines évocations jurisprudentielles, on est loin de ce qui prendrait la forme d’une « justiciabilité immédiate ». Ce qui restreint l’affirmation ex abrupto de l’énoncé d’un droit subjectif. En revanche, tout porte à croire que se développe aujourd’hui un droit du bonheur lato sensu (bonheur et bien-être associés), avec son histoire, sa doctrine, ses textes de référence et des modalités applicatives qui se donnent à lire comme la recherche de l’organisation des conditions juridiques et sociales propices à la poursuite du bonheur individuel et collectif.

Published
2019

132. Fruit and Leaf Response to Different Source–Sink Ratios in Apple, at the Scale of the Fruit-Bearing Branch

Author

Mickaël Delaire, Gerhard Buck-Sorlin, Christian leMorvan, Emna Bairam, Unité de recherche Plantes et Systèmes de Culture Horticoles (PSH), Institut National de la Recherche Agronomique (INRA), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Région Pays de la Loire 2012-2016., and AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA)

Subjects
0106 biological sciences, 0301 basic medicine, Plant Science, 01 natural sciences, Sink (geography), Carbon assimilation, functional- structural plant modeling, Cultivar, feuille végétal, source–sink ratio, [SDV.SA.HORT]Life Sciences [q-bio]/Agricultural sciences/Horticulture, Original Research, geography.geographical_feature_category, Vegetal Biology, defoliation, Microbiology and Parasitology, croissance des plantes, analyse de système, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, Microbiologie et Parasitologie, Agricultural sciences, Horticulture, pomme, espèce modèle, port de la végétation, Shoot, Bio-informatique, Malus x domestica Borkh, utilisation du temps, Bioinformatics, functional-structural plant modeling, apple, Biology, lcsh:Plant culture, Photosynthesis, 03 medical and health sciences, Girdling, lcsh:SB1-1110, photosynthèse, arbre fruitier, source-sink ratio, Source sink, geography, photosynthesis, branch, fruit growth, 15. Life on land, 030104 developmental biology, Source strength, expression pattern, malus domestica borkh, Biologie végétale, Sciences agricoles, 010606 plant biology & botany
Abstract

International audience; Apple fruit growth is the result of several factors: inherent demand (relative sink strength) of the fruit (defined by the demands for cell division and expansion growth, etc.), carbon assimilation by the source leaves (source strength), and the resulting allocation to the organ in question. It is thus a complex process involving source-sink interactions. In the present study, we designed an experimental system in which parts of fruit-bearing branches of two apple cultivars ("Fuji" and "Ariane") were isolated from the rest of the tree by girdling and then subjected to specific pruning and fruit removal treatments to create a wide range of global (branch-level) source-sink ratios. We monitored not only fruit kinetics but also photosynthesis as a response to light in leaves of the three different shoot types (i.e., the rosette, the bourse, and the vegetative shoots) to 1) study the impact of source-sink distance on carbon partitioning between fruits within the same branch and 2) to investigate the impact of source/sink ratio on fruit growth and leaf photosynthetic activity. Our results indicate 1) no significant differences among lateral fruits belonging to different ranks, and this independent of source availability; 2) that a modification of the source/sink ratio seems to be compensated by an alteration of the photosynthetic rate of leaves, with stronger and weaker values obtained for lower and higher ratios, respectively. Moreover, our results seem to suggest that two growing sinks together will upregulate photosynthesis rate more strongly than one growing sink does on its own, and this with the same leaf area per fruit. These results are discussed, and some hypotheses are put forward to explain them.

Published
2019

133. La céramique médiévale et moderne en Vendée et dans le sud de la Loire-Atlantique (Xe-milieu du XVIIe siècle)

Author

Grenouilleau, Sarah, Centre de Recherche en Archéologie, Archéosciences, Histoire (CReAAH), Le Mans Université (UM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), Université de Nantes (UN)-Université de Nantes (UN)-Ministère de la Culture (MC), Université de Nantes (UN), Région Pays de la Loire, Université de Nantes, Martial Monteil, Yves Henigfeld, Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR Histoire, Histoire de l'Art et Archéologie (UFR HHAA), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Nantes Université (NU), Université de Nantes (UN)-Le Mans Université (UM)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)

Subjects
Ceramics, supply, Moyen Âge, beginning of the Modern Era, Territoires Spécialité : Archéologie, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, approvisionnement, Sociétés, chrono-typology, Pays de la Loire, Temps, chrono-typologie, utilisation, [SHS]Humanities and Social Sciences, début de l’Époque moderne, France, Middle Ages, use, [SHS.HIST]Humanities and Social Sciences/History, céramique
Abstract

This study presents the evolution of the ceramics in Vendée and in the south of Loire-Atlantique (France) from the 10th to the middle of the 17th century. It is based on the analysis of 9 sets, corresponding to a total of 38 214 shards, from consumption sites that have castral, seigneurial, religious or rural nature. Among them, 8 lots are the subject of a particular typo-chronological analysis, based on the preliminary establishment of technical and morphological director. The collected data, which are combined with those of 30 comparison sites located in the studied area, contribute to the implementation of a general chrono-typology. Thus, it offers a better perception of the development of the shapes of the containers and the productions in use in Vendée and in the south of Loire-Atlantique during seven and a half centuries. In addition, these data are compared to the corpus of sites located in the north of Loire-Atlantique, Brittany, Charente- Maritime and Deux-Sèvres, in order to specify the differences and similarities between the containers used in these different areas. These considerations lead to the question of the supply of sites and the identification of the origin of certain containers, as well as the determination of several areas of cultural and manufacturing traditions. The changes and the gradual diversifications of ceramics over time, related to their adaptation to new eating habits, allowing, finally, to evoke the evolution of culinary and table practices.; Cette étude présente l’évolution de la céramique en Vendée et dans le sud de la Loire-Atlantique du Xe au milieu du XVIIe siècle, restituée à partir de l’analyse de 9 ensembles, correspondant à un total de 38 214 tessons, provenant de sites de consommation de nature castrale, seigneuriale, religieuse ou rurale. Parmi eux, 8 lots font l’objet d’une analyse typo-chronologique particulière, fondée sur l’établissement préalable d’un répertoire technique et morphologique. Les données recueillies, combinées à celles de 30 sites de comparaison localisés dans l’espace étudié, participent à la mise en place d’une chrono-typologie générale, offrant ainsi une meilleure perception du développement des formes des contenants et des productions en usage en Vendée et dans le sud de la Loire-Atlantique durant sept siècles et demi. Par ailleurs, ces données sont comparées aux corpus de sites localisés dans le nord de la Loire-Atlantique, la Bretagne, la Charente-Maritime et les Deux-Sèvres, afin de préciser les différences et les ressemblances entre les récipients utilisés dans ces différents secteurs. Ces réflexions conduisent à la question de l’approvisionnement des sites et à l’identification de la provenance de certains contenants, ainsi qu’à la détermination de plusieurs aires de traditions culturelles et de fabrication. Les modifications et la diversification progressive des céramiques au cours du temps, liées à leur adaptation aux nouvelles habitudes alimentaires, permettent enfin d’évoquer l’évolution des pratiques culinaires et de la table.

Published
2018

134. Stability of the adeno-associated virus 8 reference standard material

Author

Frédéric Broucque, Magalie Penaud-Budloo, Katell Harrouet, Susan M. D'Costa, Mohammed Bouzelha, Martin Lock, Richard O. Snyder, Véronique Blouin, Sandy Douthe, Eduard Ayuso, Sylvie Saleun, Oumeya Adjali, Sushma Ogram, Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Brammer Bio [Alachua, FL, USA], Department of Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Perelman School of Medicine), University of Pennsylvania [Philadelphia], Financial support to E.A.’s laboratory was provided by INSERM, University of Nantes, CHU of Nantes, Fondation d’Entreprises pour la Thérapie Génique en Pays de la Loire, and Région Pays de la Loire and Pre-industrial gene therapy consortium (Agence Nationale de la Recherche - Investissements d’Avenir, grant number 10-DPBS-0001)., ANR-10-DPBS-0001,PGT,Consortium préindustriel des vecteurs de thérapie génique(2010), University of Pennsylvania, JAULIN, Nicolas, and Démonstrateurs - Consortium préindustriel des vecteurs de thérapie génique - - PGT2010 - ANR-10-DPBS-0001 - DPBS - VALID

Subjects
0301 basic medicine, Serotype, [SDV]Life Sciences [q-bio], Genetic Vectors, Biology, medicine.disease_cause, Virus Replication, Virus, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Dosing, Vector (molecular biology), Molecular Biology, Reference standards, Adeno-associated virus, Cryopreservation, Protein Stability, Dependovirus, Reference Standards, Virology, 3. Good health, [SDV] Life Sciences [q-bio], Titer, 030104 developmental biology, HEK293 Cells, Capsid, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Molecular Medicine, Capsid Proteins
Abstract

International audience; Adeno-associated virus (AAV) vectors are extensively used for gene therapy clinical trials. Accurate and standardized titration methods are essential for characterizing and dosing AAV-based drugs and thus to assess their safety and efficacy. To this end, the Reference Standard Materials (RSM) working group generated standards for AAV serotype 2 and serotype 8. The AAV8RSM (ATCC® VR-1816™) was deposited to the American Type Culture Collection in 2014 and is available to the scientific community. Here, three independent laboratories of the RSM working group provide stability data of the AAV8RSM 2 years after the initial characterization and after container relabeling performed at the ATCC. The AAV8RSM showed constant titers across experimental conditions: 1.48 ± 0.62 × 1012 vector genome (vg)/ml, 9.38 ± 11.4 × 108 infectious units (IU)/ml and 5.76 ± 2.39 × 1011 total particles (p)/ml as determined by qPCR, TCID50 and ELISA, respectively. Additionally, the AAV8RSM capsid protein integrity assessed by SDS-PAGE was equivalent to the original analyses. In conclusion, the AAV8RSM titers remained stable for two years under appropriate storage conditions (

Published
2018

135. De la machine à l'expert(e) libéré(e) : l'idéal du professionnel comptable moderne selon la publicité. Une étude des représentations du professionnel comptable par l'analyse des publicités parues dans la Revue Française de Comptabilité de 1955 à 2017

Author

Bournel, Benjamin, Groupe de Recherche Angevin en Economie et Management (GRANEM), Université d'Angers (UA)-AGROCAMPUS OUEST-Institut National de l'Horticulture et du Paysage, Région Pays de la Loire, Université d'Angers, Sébastien Rocher, Université d'Angers (UA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de l'Horticulture et du Paysage

Subjects
représentation, [SHS.GESTION]Humanities and Social Sciences/Business administration, profession comptable, accounting profession, identity, identité
Abstract

The goal of this doctoral research is to analyze the successive transformations of perceived image of what is an accountant in advertising aimed at them. Based on the study of advertisements published in the Revue française de comptabilité from 1955, creation date of journal by the French Order of Chartered Accountants, to 2017, the transformations of the constituent elements of the central core and the peripheral elements of accounting professionals social representations, have been analysed, in accordance with Abric’s theory (1984).To do this, a semiological studyof advertissements was favored, based on the joint analysis of their denoted and connoted message. The results of this research show that in sixty years, the ideal of the accounting professional has gone from the machine domination to an expert in social relations, looking for pleasure at work and his or her life.It thus appears that successive technological changes in the accounting profession have contributed to the modernization of the image of what an accountant should be. The managerial interest of this research is to enable the accounting profession to better understand its perceived image in order to better control it. In doing so, this study also questions the effects of advertising the professional accountants their professional identity definition. .; Le but de cette recherche doctorale est d’analyser les transformations successives de l’image perçue de ce qu’est un professionnel comptable dans les publicités qui leur sont adressées. À partir de l’étude des publicités parues dans la revue française de comptabilité de 1955, soit sa date de création par l’Ordre des experts-comptables, à 2017, l’évolution des éléments centraux et périphériques de ces représentations a été analysée en accord avec la théorie du noyau central élaborée par Abric (1984). Pour ce faire, une étude sémiologique a été privilégiée, fondée sur l’analyse conjointe des messages dénotés et connotés de ces publicités. Les résultats de cette recherche montrent qu’en soixante ans, l’idéal du professionnel comptable est passé d’un individu inféodé à la machine à un expert des relations sociales, orienté aujourd’hui vers une quête de son plaisir au travail et dans sa vie privée, une transformation apparue au rythme des mutations technologiques qui ont émaillé l’histoire de la profession comptable. Sur le plan managérial, l’enjeu de cette recherche est de permettre à la profession comptable de mieux comprendre son image perçue pour mieux la maîtriser. Ce faisant, elle questionne les effets des publicités à l’attention des professionnels comptables sur la définition de leur identité professionnelle.

Published
2018

136. From the Machine to the Relaxed Expert: The Ideal of Modern Accountant Professionnal according to Advertising. A study of Accounting Professionnal Representations in the Advertising published in the Revue Française de Comptabilité from 1955 to 2017

Author

Bournel, Benjamin, Groupe de Recherche Angevin en Economie et Management (GRANEM), Université d'Angers (UA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de l'Horticulture et du Paysage, Région Pays de la Loire, Université d'Angers, and Sébastien Rocher

Subjects
représentation, [SHS.GESTION]Humanities and Social Sciences/Business administration, profession comptable, accounting profession, identity, identité
Abstract

The goal of this doctoral research is to analyze the successive transformations of perceived image of what is an accountant in advertising aimed at them. Based on the study of advertisements published in the Revue française de comptabilité from 1955, creation date of journal by the French Order of Chartered Accountants, to 2017, the transformations of the constituent elements of the central core and the peripheral elements of accounting professionals social representations, have been analysed, in accordance with Abric’s theory (1984).To do this, a semiological studyof advertissements was favored, based on the joint analysis of their denoted and connoted message. The results of this research show that in sixty years, the ideal of the accounting professional has gone from the machine domination to an expert in social relations, looking for pleasure at work and his or her life.It thus appears that successive technological changes in the accounting profession have contributed to the modernization of the image of what an accountant should be. The managerial interest of this research is to enable the accounting profession to better understand its perceived image in order to better control it. In doing so, this study also questions the effects of advertising the professional accountants their professional identity definition. .; Le but de cette recherche doctorale est d’analyser les transformations successives de l’image perçue de ce qu’est un professionnel comptable dans les publicités qui leur sont adressées. À partir de l’étude des publicités parues dans la revue française de comptabilité de 1955, soit sa date de création par l’Ordre des experts-comptables, à 2017, l’évolution des éléments centraux et périphériques de ces représentations a été analysée en accord avec la théorie du noyau central élaborée par Abric (1984). Pour ce faire, une étude sémiologique a été privilégiée, fondée sur l’analyse conjointe des messages dénotés et connotés de ces publicités. Les résultats de cette recherche montrent qu’en soixante ans, l’idéal du professionnel comptable est passé d’un individu inféodé à la machine à un expert des relations sociales, orienté aujourd’hui vers une quête de son plaisir au travail et dans sa vie privée, une transformation apparue au rythme des mutations technologiques qui ont émaillé l’histoire de la profession comptable. Sur le plan managérial, l’enjeu de cette recherche est de permettre à la profession comptable de mieux comprendre son image perçue pour mieux la maîtriser. Ce faisant, elle questionne les effets des publicités à l’attention des professionnels comptables sur la définition de leur identité professionnelle.

Published
2018

137. Dirac brushes (or, the fractional Fourier transform of Dirac combs)

Author

Viola, Joe, Equations aux dérivées partielles, Laboratoire de Mathématiques Jean Leray (LMJL), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), and Région Pays de la Loire through the project EONE (Évolution des Opérateurs Non-Elliptiques)

Subjects
42A16, 81S30, 11F27, 11F30, poisson summation, Mathematics - Number Theory, Mathematics - Classical Analysis and ODEs, MSC 42A16, 81S30, 11F27, 11F30, Classical Analysis and ODEs (math.CA), FOS: Mathematics, theta function, Number Theory (math.NT), metaplectic representation, [MATH.MATH-CA]Mathematics [math]/Classical Analysis and ODEs [math.CA], fractional Fourier transform, [MATH.MATH-NT]Mathematics [math]/Number Theory [math.NT]
Abstract

In analogy with the Poisson summation formula, we identify when the fractional Fourier transform, applied to a Dirac comb in dimension one, gives a discretely supported measure. We describe the resulting series of complex multiples of delta functions, and through either the metaplectic representation of $SL(2,\mathbb{Z})$ or the Bargmann transform, we see that the the identification of these measures is equivalent to the functional equation for the Jacobi theta functions. In tracing the values of the antiderivative in certain small-angle limits, we observe Euler spirals, and on a smaller scale, these spirals are made up of Gauss sums which give the coefficient in the aforementioned functional equation., 42 pages, 7 figures

Published
2018

138. Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma

Author

Bensaid, Douae, Blondy, Thibaut, Deshayes, Sophie, Dehame, Virginie, Bertrand, Philippe, Grégoire, Marc, Errami, Mohammed, Blanquart, Christophe, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratory of Physiology and Physiopathology [Tetouan, BP, Morocco], Faculty of Sciences of Tetouan [Morocco], Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Membre du Réseau Epigénétique du Cancéropôle Grand-Ouest, This work was supported by INSERM, CNRS, Région Pays de la Loire, the 'Institut de recherche en santé respiratoire des Pays de la Loire', the ‘Ligue Contre le Cancer (committees of Morbihan, Sarthe, Vendée et Loire-Atlantique), ARSMESO44, Nantes University Hospital, and INSERM (France)/ CNRST (Morocco) agreement 2015/2016., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
Male, Mesothelioma, PD-L1, Lung Neoplasms, lcsh:QH426-470, Cell Survival, Malignant pleural mesothelioma, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Decitabine, Hydroxamic Acids, T-Lymphocytes, Regulatory, B7-H1 Antigen, Epigenesis, Genetic, CD8+ T-cell clone, [SDV.CAN] Life Sciences [q-bio]/Cancer, HDAC inhibitors, Cell Line, Tumor, Humans, Cell Proliferation, Vorinostat, Dose-Response Relationship, Drug, Decitabine (5-aza-2′-deoxycytidine), Valproic Acid, Research, Mesothelioma, Malignant, lcsh:R, DNA Methylation, Gene Expression Regulation, Neoplastic, Histone Deacetylase Inhibitors, Killer Cells, Natural, lcsh:Genetics, Benzamides, Epigenetic drugs, Drug Therapy, Combination, Immunotherapy, Tumor antigen
Abstract

Background Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma. However, VPA is not very specific, is active at millimolar concentrations and is responsible for side effects in clinic. To improve this approach, we studied four newly synthetized HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB and NODB), in comparison with VPA and SAHA. We evaluated their toxicity on immune cells and their immunogenicity on MPM cells in combination with decitabine. Results All the tested HDACi were toxic for immune cells at high concentrations. Combination with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease in the proportion of regulatory T cells and natural killer cells was observed in particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO-1 cancer testis antigen (CTA) expression and the recognition of the treated cells by a NY-ESO-1 specific T-CD8 clone. However, for MAGE-A1, MAGE-A3 and XAGE-1b mRNA expression, the results obtained depended on the HDACi used and on the CTA studied. Depending on the MPM cell line studied, molecules alone increased moderately PD-L1 expression. When combined, a higher stimulation of this immune check point inhibitor expression was observed. Decitabine-induced anti-viral response seemed to be inhibited in the presence of HDACi. Conclusions This work shows that the combination of decitabine and HDACi could be of interest for MPM immunotherapy. However, this combination induced PD-L1 expression which suggests that an association with anti-PD-L1 therapy should be performed to induce an efficient anti-tumor immune response. Electronic supplementary material The online version of this article (10.1186/s13148-018-0517-9) contains supplementary material, which is available to authorized users.

Published
2018

139. Specific or not specific recruitment of DNMTs for DNA methylation, an epigenetic dilemma

Author

Hervouet, Eric, Peixoto, Paul, Delage-Mourroux, Régis, Boyer-Guittaut, Michaël, Cartron, Pierre-François, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), EPIgenetics and GENe EXPression Technical Plateform (EPIGENExp), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Réseau Epigénétique du Cancéropôle Grand-Ouest [Nantes] (REpiCGO), Cancéropôle Grand Ouest [Nantes]-Maison de la Recherche en Santé [Nantes], Epigénétique - Santé - AgroAlimentaire - Végétal - Mer - Environnement - Nutrition [Nantes] (EpiSAVMEN), Consortium de la Recherche en Epigénétique de la Région Pays de la Loire [Nantes], This work was supported by the University of Franche-Comté, 'Ministère de l’Enseignement Supérieur et de la Recherche' (MESR) and fundings from CCIR-GE 'Ligue Contre le Cancer' and 'Région de Franche-Comté'., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
DNA Replication, DNA methylation, lcsh:QH426-470, DNMT3L, lcsh:R, DNMT1, Embryonic Development, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Epigenesis, Genetic, lcsh:Genetics, [SDV.CAN] Life Sciences [q-bio]/Cancer, DNMT-including complexes, embryonic structures, Animals, Humans, DNMT3A, Epigenetics, DNMT3B, DNA (Cytosine-5-)-Methyltransferases
Abstract

International audience; Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes. For example, the DNMT3L/DNMT3A complex is mainly related to de novo DNA methylation in embryonic states, whereas the DNMT1/PCNA/UHRF1 complex is required for maintaining global DNA methylation following DNA replication. On the opposite to these unspecific DNA methylation machineries (no preferential DNA sequence), some recently identified DNMT-including complexes are recruited on specific DNA sequences. The coexistence of both types of DNA methylation (un/specific) suggests a close cooperation and an orchestration between these systems to maintain genome and epigenome integrities. Deregulation of these systems can lead to pathologic disorders.

Published
2018

140. Agricultural landscapes and the Loire River influence the genetic structure of the marbled newt in Western France

Author

Jean-Marc Costanzi, Quentin Le Petitcorps, Francis Isselin-Nondedeu, Pierre Grillet, Pascal Mège, Olivier Lourdais, Sophie Morin-Pinaud, Agathe Legrand, François Varenne, Audrey Trochet, Alexandre Boissinot, Damien Picard, Sandra Guérin, Faculty of Technology, Natural Sciences and Maritime Sciences [Norway], University of South-Eastern Norway (USN), Département de Biologie UFR Sciences - Université d'Angers [France], Université d'Angers (UA), Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cités, Territoires, Environnement et Sociétés (CITERES), Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), Evolution et Diversité Biologique (EDB), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Station d'écologie théorique et expérimentale (SETE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), LPO Vendée, LPO, Pierre Grillet, Unité Avifaune migratrice, Direction de la Recherche et de l’Expertise (ONCFS France], Office National de la Chasse et de la Faune Sauvage (ONCFS), Région Pays de la Loire, Centre Beautour, Chinon SNB project (stratégie nationale pour la biodiversité 2011, French minister of ecology), Office National de la Chasse et de la Faune Sauvage (Pôle Bocage et Faune Sauvage) and Nouvelle-Aquitaine Region, ONF-Centre Val de Loire, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de La Rochelle (ULR), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), ONCFS - Office National de la Chasse et de la Faune Sauvage, Centre National de la Recherche Scientifique (CNRS)-Université de Tours, Institut National de la Recherche Agronomique (INRA)-La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, 0301 basic medicine, Biodiversité et Ecologie, Science, Triturus marmoratus, Loire River, 010603 evolutionary biology, 01 natural sciences, Biodiversity and Ecology, 03 medical and health sciences, DAPC Results, Discriminant Analysis Of Principal Components (DAPC), Isolation by distance, Multidisciplinary, biology, Ecology, Marbled Newt, Fragmentation (computing), 15. Life on land, biology.organism_classification, Large Crop Fields, 030104 developmental biology, Geography, Genetic distance, Genetic structure, [SDE]Environmental Sciences, Medicine, Biological dispersal, Conservation biology, Arable land
Abstract

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Amphibians are particularly sensitive to landscape fragmentation. Potential barriers between breeding sites can negatively infuence the dispersal of individuals and increase genetic structure between populations. In this study, we genotyped 10 microsatellites for 334 marbled newts (Triturus marmoratus) at 11 diferent locations in Western France. Samples were collected in diferent regions with contrasting agricultural landscapes (low and high proportion of arable land in the north and south, respectively). We found a strong genetic structure between the northern and southern sampling sites. Isolation by distance was recorded after 62km, but within the northern region, little or no genetic structure was detected over large distances (up to 114km). Genetic structure at shorter distance (43km) was found between sites situated in landscapes with larger amounts of arable lands. A signifcant positive relationship was found between the pairwise genetic distance (Fst) between sites and the amount of arable land together with the distance between sites. Our results suggest that the Loire River might act as a corridor for the marbled newt, while arable land might act as a barrier. Finally, although a large city is located between sampling sites, no efect was detected on population structure.

Published
2018

141. Relative importance of management and natural flooding on spider, carabid and plant assemblages in extensively used grasslands along the Loire

Author

Denis Lafage, Julien Pétillon, Groupe ECologie et COnservation des vertébrés (GECCO), Université d'Angers (UA), Biodiversité et gestion des territoires EA 7316, Région Pays de la Loire, Plan Loire Grandeur Nature, and Agence de l’Eau Loire-Bretagne

Subjects
0106 biological sciences, 2. Zero hunger, Cutting-date, Gradient analysis, Ecology, [SDV]Life Sciences [q-bio], 010604 marine biology & hydrobiology, Coleoptera Carabidae, Flooding (psychology), Community structure, Vegetation, Stochastic disturbance, 15. Life on land, 010603 evolutionary biology, 01 natural sciences, Productivity (ecology), 13. Climate action, Abundance (ecology), Araneae, Environmental science, Alluvium, Ecosystem, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Fertilizers, Ecology, Evolution, Behavior and Systematics
Abstract

International audience; In Europe, agri-environment schemes (AES) have been implemented to counteract the effects of agricultural intensification. Studies investigating the role of management improvement induced by AES are quite numerous, but rarely take into account the effect of natural perturbations such as flooding, although severe disturbances are well known to shape community structure. Here we investigated the relative importance of management improvement and flooding to explain community parameters of two dominant arthropod groups and vegetation in alluvial meadows. Sampling took place in 2013, using suction samplers for arthropods and phytosociological relevés for vegetation, in 83 meadows distributed along 200 km of the Loire Valley (France). Pair-matched approach (by R-ANOVA) was used to assess overall effects of AES whereas a gradient analysis (GLM) was carried out to assess the impact of AES prescriptions (fertilisation and cutting-date) together with indirect (long-term) and direct (short-term) effects of flooding. No significant effect of AES was found on arthropod and plant assemblages, abundance/productivity or diversity (both α and β), but the number of rare plant species was higher in sites under AES. Prescriptions had little impact on most response variables considered; the only significant impact being the positive effect of high-amounts of fertilisers on spider α- and β-diversities. Conversely, systematic long-term effects of flooding were found on all response variables of spiders, carabids and plants, underlining the key role of this factor in alluvial meadows. Our study demonstrates that maintaining or enhancing hydrological functioning of ecosystems is even more important than regulating both the cutting-dates and the low input of fertilisers for conservation purposes in flooded, already naturally nutrient rich, meadows

Published
2016

142. Localization versus Delocalization in Chiral Single Component Conductors of Gold Bis(dithiolene) Complexes

Author

Enric Canadell, Rodolphe Clérac, Diana G. Branzea, Narcis Avarvari, Flavia Pop, Pere Alemany, Pascale Auban-Senzier, Chimie, Ingénierie Moléculaire et Matériaux d'Angers (CIMMA), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), MOLTECH-Anjou, Université d'Angers (UA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de recherches Paul Pascal (CRPP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universitat de Barcelona (UB), Institut de Ciència de Materials de Barcelona (ICMAB), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Ministerio de Economica y Competitividad (Grant FIS2012-37549-C05-05, FIS2015-64886-C5-4-P and CTQ2015-64579- C3-3-P) and Generalitat de Catalunya (2014SGR301 and XRQTC)Université d'Angers, Région Pays de la Loire, ANR-12-IS07-0004,CREMM,Ingénierie Cristalline de Matériaux Moléculaires Multifonctionnels(2012), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche (France), Région des Pays de la Loire, Centre National de la Recherche Scientifique (France), Université de Bordeaux, Conseil régional d'Aquitaine, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, and Universitat de Barcelona

Subjects
Inorganic chemistry, chemistry.chemical_element, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, Solid state chemistry, Metal, Delocalized electron, Electric conductivity, Colloid and Surface Chemistry, Metal complexes, [CHIM]Chemical Sciences, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Isostructural, ComputingMilieux_MISCELLANEOUS, Chemistry, Ligand, Hydrogen bond, Intermolecular force, Conductivitat elèctrica, [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, Ciència dels materials, 021001 nanoscience & nanotechnology, Complexos metàl·lics, Materials science, 0104 chemical sciences, 3. Good health, Química de l'estat sòlid, Nickel, Crystallography, visual_art, visual_art.visual_art_medium, 0210 nano-technology, Single crystal
Abstract

The first examples of chiral single component conductors are reported. Both (S,S) and (R,R) enantiomers of 5,6-dimethyl-5,6-dihydro-1,4-dithiin-2,3-dithiolate (dm-dddt) ligand have been used to prepare anionic metal bis(dithiolene) complexes formulated as ([(n-Bu)4N][M(dm-dddt)2] (M = Au, Ni), which are isostructural according to single crystal X-ray analysis. Single crystal transport measurements indicate semiconducting behavior for the anionic radical Ni complexes, with low room temperature conductivity values and high activation energies. Electrocrystallization experiments provided neutral [M(dm-dddt)2] (M = Au, Ni) complexes. The neutral radical gold compounds show intermolecular S···S interactions in the solid state giving rise to layers interconnected through weak C–H···S hydrogen bonds. The most peculiar structural feature concerns a dissymmetry between the two dithiolene moieties, while the nickel counterpart is symmetric. Single crystal resistivity measurements show thermally activated behavior for the open-shell gold complexes, with room temperature conductivity values of 0.02–0.04 S·cm–1 and activation energies strongly influenced by hydrostatic pressure. A thorough theoretical study on nickel anion radical and gold neutral radical bis(dithiolene) complexes applied to the chiral complexes [M(dm-dddt)2] (M = Au, Ni–) and to a series of previously reported compounds addressed the issue of symmetry versus asymmetry from an electronic coupling perspective between the two dithiolene ligands. It results that neutral gold complexes with dithiolene ligands without extended delocalization are Class II mixed-valent compounds in the Robin and Day classification, presenting an inherent tendency toward asymmetric structures, which can be however modulated by the intermolecular organization in the solid state., This work was supported in France by the National Agency for Research (ANR Inter, ANR-12-IS07-0004-04, CREMM Project), the Region Pays de la Loire (grant for D.B.), the CNRS, the University of Angers, the University of Bordeaux and the Aquitaine Region. Work in Spain was supported by the Spanish Ministerio de Economía y Competitividad (Grants FIS2012- 37549-C05-05, FIS2015-64886-C5-4-P and CTQ2015-64579- C3-3-P) and Generalitat de Catalunya (2014SGR301 and XRQTC). E.C. acknowledges support of the Spanish MINECO through the Severo Ochoa Centers of Excellence Program under Grant SEV-2015-0496.

Published
2016

143. Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft Rejection

Author

Jeremy Hervouet, Karine Renaudin, David Minault, Nicolas Poirier, Sabrina Pengam, Steven Nedellec, Caroline Mary, Vianney Charpy, Véronique Nerrière-Daguin, Julien Branchereau, Stéphanie Le Bas-Bernardet, Bernard Vanhove, Simon Ville, Alexis Chenouard, Gilles Blancho, Flora Coulon, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Effimune SAS [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Cellular and Tissular Imaging Core Facility of Nantes (MicroPICell), Université de Nantes (UN), IHU-Cesti, région Pays de la Loire et Nantes Métropole., ANR: ANR-10-IBHU005, Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, and ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010)

Subjects
lymphocytes, Graft Rejection, 0301 basic medicine, Regulatory T cell, medicine.medical_treatment, kidney transplantation, chemical and pharmacologic phenomena, 030230 surgery, Biology, acute rejection, Belatacept, Antibodies, immunology, Abatacept, Mice, 03 medical and health sciences, 0302 clinical medicine, CD28 Antigens, medicine, Animals, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, immunosuppression, CD28, hemic and immune systems, General Medicine, Tacrolimus, 3. Good health, Basic Research, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Nephrology, Immunology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Immunosuppressive Agents, CD80, Papio, medicine.drug, Allotransplantation
Abstract

International audience; Belatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 and its alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesting that blocking CTLA-4 is deleterious. We performed a head to head assessment of FR104 (n=5), a selective pegylated Fab9 antibody fragment antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboons. The biologics were supplemented with an initial 1-month treatment with low-dose tacrolimus. In cases of acute rejection, animals also received steroids. In the belatacept group, four of five recipients developed severe, steroid-resistant acute cellular rejection, whereas FR104-treated animals did not. Assessment of regulatory T cell-specific demethylated region methylation status in 1-month biopsy samples revealed a nonsignificant trend for higher regulatory T cell frequencies in FR104-treated animals. Transcriptional analysis did not reveal significant differences in Th17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals. In vitro, FR104 controlled the proliferative response of human preex-isting Tfh cells more efficiently than belatacept. In mice, selective CD28 blockade also controlled Tfh memory cell responses to KLH stimulation more efficiently than CD80/86 blockade. Our data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of renal allograft rejection, particularly at the level of Tfh cell stimulation.

Published
2016

144. IL-9 promotes the survival and function of human melanoma-infiltrating CD4+CD8+double-positive T cells

Author

Nathalie Labarrière, Yves Delneste, Nadine Gervois, Romain Oger, Houssem Benlalam, Diane Raingeard de la Blétière, Tiphaine Parrot, Amir Khammari, Laurence Preisser, Mathilde Allard, Anne Coutolleau, Juliette Desfrançois, Philippe Guardiola, Brigitte Dréno, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Plateforme SNP, Transcriptome & Epigénomique, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Plateforme CYTOCELL Nantes (CRCINA-CYTOCELL), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), GMP Unit of Cellular Therapy, Centre hospitalier universitaire de Nantes (CHU Nantes), Unit of Skin Cancer, Canceropole Grand Ouest, Région Pays de la Loire, ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, and Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID

Subjects
CD4-Positive T-Lymphocytes, Cytotoxicity, Immunologic, 0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cell Survival, Immunology, Gene Expression, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, CD8-Positive T-Lymphocytes, Biology, Lymphocyte Activation, 03 medical and health sciences, Interleukin 21, Lymphocytes, Tumor-Infiltrating, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, T-Lymphocyte Subsets, Humans, Immunology and Allergy, Cytotoxic T cell, Interleukin 9, Melanoma, Cells, Cultured, Receptors, Interleukin-9, Interleukin-9, Degranulation, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, T lymphocyte, 3. Good health, Granzyme B, 030104 developmental biology, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, CD8
Abstract

International audience; We previously demonstrated an accumulation of tumor-reactive CD4 + CD8 + double positive (DP) T cells within melanoma-infiltrating lymphocytes, supporting their role in the regulation of anti-tumor immune responses. Similarly to their CD8 + counterparts, intra-tumor DP T cells are MHC class-I restricted but differed by a limited lytic activity against autologous melanoma cells. Based on these observations and to further characterize DP T cells, both populations were compared at the transcriptional level. Our results revealed the overexpression of the IL-9 receptor (IL-9R) by DP T cells and prompted us to investigate the impact of IL-9 on their biology. We show that IL-9 favors DP T-cell survival by protecting them from apoptosis and by promoting their proliferation. In addition, IL-9 enhances their ability to produce cytokines and increased their levels of granzyme B/perforin as well as degranulation capacity, leading to a strengthened cytotoxic activity against melanoma cells. Taken together, the IL-9R high DP T-cell population could be a new preferential target for IL-9, which could take part in their retention within the melanoma infiltrate while also favoring their anti-tumor activity. More generally, our results extend the pleiotropic effects of IL-9 to IL-9R-expressing intra-tumor T cells, which could further potentiate anti-tumor immune responses. Keywords: CD4 + CD8 + double-positive T lymphocyte r IL-9R r IL-9 r Melanoma r TIL Additional supporting information may be found in the online version of this article at the publisher's web-site

Published
2016

145. Deformation of silica glass studied by molecular dynamics: Structural origin of the anisotropy and non-Newtonian behavior

Author

Xavier Bidault, Stéphane Chaussedent, Wilfried Blanc, Daniel R. Neuville, Laboratoire de Photonique d'Angers (LPHIA), Université d'Angers (UA), Laboratoire de physique de la matière condensée (LPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Région Pays de la Loire (NACRYSIM program), ANR project 'Nice-DREAM', GDR Verres, ANR-14-CE07-0016,Nice-DREAM,Etirage de matériaux amorphes dopés de nanoparticules(2014), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), and Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS)

Subjects
Materials science, Physics::Optics, 02 engineering and technology, non-Newtonian behavior, Molecular Dynamics, Condensed Matter::Disordered Systems and Neural Networks, 01 natural sciences, Glass structure, [PHYS.PHYS.PHYS-COMP-PH]Physics [physics]/Physics [physics]/Computational Physics [physics.comp-ph], Molecular dynamics, Transverse isotropy, 0103 physical sciences, Materials Chemistry, Fiber, Composite material, Anisotropy, 010302 applied physics, Elasticity (physics), 021001 nanoscience & nanotechnology, Condensed Matter Physics, Elasticity, Non-Newtonian fluid, Electronic, Optical and Magnetic Materials, Condensed Matter::Soft Condensed Matter, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Ceramics and Composites, Tetrahedron, Silica glass, Deformation (engineering), 0210 nano-technology
Abstract

International audience; A novel aspect of the medium-range structure of silica drawn into fibers is studied. The network of silica glass structure is composed of corner-shared SiO 4 tetrahedra, and it can be seen as a structure of interconnected rings (Si-O) n of various size, denoted nMR (n-Membered Ring). Molecular Dynamics simulations show that small-sized silica rings get a preferential orientation during the drawing, either during the high-temperature stage for 3MR, or during the cooling for 4MR and 5MR, and they persist in this state in the fiber at ambient temperature. This leads to a structural anisotropy, more specifically a " transverse isotropy " , because of different longitudinal and transversal physical properties. This anisotropic structural rearrangement during the drawing process induces a non-Newtonian behavior of the modeled glass melt, with strain-rate dependent properties. Highlights: Anisotropy in silica glass comes from the orientation that small silica rings acquire during the deformation. The model is in agreement with experiments (non-Newtonian behavior of the melt, anisotropic elasticity of the fiber). The anisotropy in silica fiber is a " transverse isotropy " .

Published
2016

146. Facile design of red-emitting waveguides using hybrid nanocomposites made of inorganic clusters dispersed in SU8 photoresist host

Author

Anthony Désert, Jean-Luc Duvail, John Bigeon, Alexandre Garreau, Stéphane Cordier, Nolwenn Huby, Eric Faulques, Julien Fade, Bruno Bêche, Yann Molard, Quentin Lagneaux, Maria Amela-Cortes, Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Région Pays de la Loire, CPER-FEDER 2007–2014, Région Bretagne European Union, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Photoluminescence, Materials science, 02 engineering and technology, Photoresist, 010402 general chemistry, 01 natural sciences, law.invention, Inorganic Chemistry, symbols.namesake, law, Stokes shift, Organic photonics, Electrical and Electronic Engineering, Physical and Theoretical Chemistry, Spectroscopy, Nanocomposite, business.industry, Organic Chemistry, 021001 nanoscience & nanotechnology, Atomic and Molecular Physics, and Optics, 0104 chemical sciences, Electronic, Optical and Magnetic Materials, Attenuation coefficient, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, symbols, Optoelectronics, 0210 nano-technology, business, Refractive index, Waveguide
Abstract

International audience; Integration of stable emissive entities into organic waveguide with minimum scattering is essential to design efficient optically active devices. Here we present a new class of doped nanocomposite waveguides exploiting 1-nm diameter metallic cluster-based building blocks as red-NIR luminescent dyes embedded in a SU8 polymeric matrix, a reference photoresist for organic photonics. These building blocks are [Mo6Ii8(OOCC2F5)a6]2− cluster anionic units with unique chemical and physical features well suited for optical nanocomposites such as a ligand-promoted dispersibility, a large Stokes shift with a broad absorption window and an emission window in the range 600–900 nm. A whole investigation of the nanocomposite has been first performed. Optical characterizations of Cs2[Mo6Ii8(OOCCnF2n+1)a6]@SU8 nanocomposites thin film and waveguiding structures show their relevance as active layers in integrated structures with a significant increase of the refractive index of 3 × 10−2 when the cluster concentration increases up to 4 wt%, while keeping high values for the transmitted power, as shown for different waveguide dimensions and clusters concentrations. The efficiency of photoluminescence propagation is investigated as a function of clusters concentration in the excitation area for several waveguides dimensions. Attenuation coefficient ranges between 5 and 18 dB/cm, values of the same order of magnitude as those obtained in polymeric waveguide doped with QDs or organic dyes. This original, stable and efficient nanocomposite is promising for downscaling complex nanosources and active waveguides in the visible and NIR range.

Published
2016

147. Ester Cross-Link Profiling of the Cutin Polymer of Wild-Type and Cutin Synthase Tomato Mutants Highlights Different Mechanisms of Polymerization

Author

Nathalie Geneix, Christophe Rothan, Bénédicte Bakan, Cédric Gaillard, Jean-Philippe Mauxion, Didier Marion, Johann Petit, Cécile Bres, Michèle Dalgalarrondo, Glenn Philippe, Lukas Schreiber, Rochus Franke, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Biologie du fruit et pathologie (BFP), Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Rheinische Friedrich-Wilhelms-Universität Bonn, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, and Région Pays de la Loire

Subjects
Glycerol, 0106 biological sciences, 0301 basic medicine, Polymers, Physiology, Polyesters, [SDV]Life Sciences [q-bio], Alcohol, Plant Science, Cutin, 01 natural sciences, Polymerization, Membrane Lipids, 03 medical and health sciences, chemistry.chemical_compound, Solanum lycopersicum, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Organic chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Plant Proteins, chemistry.chemical_classification, Esterification, Chemistry, Fatty Acids, fungi, Cross-link, food and beverages, Esters, Lipase, Articles, Polymer, Polyester, 030104 developmental biology, Monomer, Ethyl Methanesulfonate, Fruit, Mutation, 010606 plant biology & botany
Abstract

International audience; Cuticle function is closely related to the structure of the cutin polymer. However, the structure and formation of this hydrophobic polyester of glycerol and hydroxy/epoxy fatty acids has not been fully resolved. An apoplastic GDSL-lipase known as CUTIN SYNTHASE1 (CUS1) is required for cutin deposition in tomato (Solanum lycopersicum) fruit exocarp. In vitro, CUS1 catalyzes the self-transesterification of 2-monoacylglycerol of 9(10),16-dihydroxyhexadecanoic acid, the major tomato cutin monomer. This reaction releases glycerol and leads to the formation of oligomers with the secondary hydroxyl group remaining nonesterified. To check this mechanism in planta, a benzyl etherification of nonesterified hydroxyl groups of glycerol and hydroxy fatty acids was performed within cutin. Remarkably, in addition to a significant decrease in cutin deposition, mid-chain hydroxyl esterification of the dihydroxyhexadecanoic acid was affected in tomato RNA interference and ethyl methanesulfonate-cus1 mutants. Furthermore, in these mutants, the esterification of both sn-1,3 and sn-2 positions of glycerol was impacted, and their cutin contained a higher molar glycerol-to-dihydroxyhexadecanoic acid ratio. Therefore, in planta, CUS1 can catalyze the esterification of both primary and secondary alcohol groups of cutin monomers, and another enzymatic or nonenzymatic mechanism of polymerization may coexist with CUS1-catalyzed polymerization. This mechanism is poorly efficient with secondary alcohol groups and produces polyesters with lower molecular size. Confocal Raman imaging of benzyl etherified cutins showed that the polymerization is heterogenous at the fruit surface. Finally, by comparing tomato mutants either affected or not in cutin polymerization, we concluded that the level of cutin cross-linking had no significant impact on water permeance.

Published
2015

148. Critical cartography of geographic realities: cas of marine spatial planning

Author

Leroy, Yannick, Littoral, Environnement, Télédétection, Géomatique UMR 6554 (LETG), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN), COSELMAR (Région Pays de la Loire), Université de Nantes, Paul Fattal, Brice Trouillet (co-directeur), Claude Rioux (co-directeur), and Université du Québec à Rimouski (UQAR)

Subjects
planification spatiale marine, Cartographie critique, pêches maritimes, spatial justice, planning & development, fisheries, [SHS.GEO]Humanities and Social Sciences/Geography, Critical cartography, marine spatial planning, aménagement, deep mapping, justice spatiale
Abstract

The Marine Spatial Planning (MSP) is the new device from modern states looking to manage marine space within their maritime jurisdictions. MSP relies on the knowledge of some scientific disciplines and the power of geo-technologies (ex. GIS) to inform and map the existing conditions of the sea. Like numerous other normative management frameworks of geographic space, this device uses the acquisition, the treatment and the cartographic representation of the data pertaining to the human (activities) and non-human (ecosystem) world to make decisions, here offshore. A certain geographic reality is hence established by the information gained from this mapping. Yet, in these specific conditions, a "missing layer" was observed: a "social and human landscape" was shaped by fishing activities. Therefore, this research on human geography aims to inform and map this “missing layer” by using exploratory, qualitative, and comparative methods. This allow to make visible another existing and observable geographic reality into the sea. This is a matter of a complex and dynamic gathering of discrete and sensible places, linked by sociotechnical fishing practices, emerging dynamic territories. Also the information and mapping of this “missing layer” therefore permits for the questioning of the real ins and outs of MSP in action, to bring to light spatial justice issues which it does emerge and to open geographic horizons for the mobilization of this other geographic reality. In sum, the information and mapping of “missing layer” are one of the multiple democratic issues of the beginning of this 21th century.; La Planification Spatiale Marine (PSM) est le nouveau dispositif des États modernes cherchant à aménager l’espace marin au sein de leurs juridictions maritimes nationales. Pour ce faire, la PSM repose sur les connaissances de certaines disciplines scientifiques et la puissance des géo-technologies (ex. SIG) pour informer et cartographier les conditions existantes en mer. Comme de nombreux contextes normatifs d’aménagement de l’espace géographique, ce dispositif centre son exercice décisionnel sur l’acquisition, le traitement et la représentation cartographique de données relatives aux monde humain (activités) et non-humain (écosystèmes), ici en mer. Leur information et cartographie instituent ainsi sur plan, une certaine réalité géographique. Or dans ces conditions particulières, il a été constaté une "couche manquante" d’informations : un "paysage humain et social" produit notamment par les activités de pêche en mer. Ce travail de thèse de géographie humaine vise à informer et cartographier cette "couche manquante" par une démarche exploratoire, qualitative et comparative. Celle-ci permet de rendre visible une autre réalité géographique existante et observable en mer. Il s’agit d’un assemblage complexe et dynamique de lieux discrets et sensibles, liés par des pratiques sociotechniques de pêche, faisant émerger des territorialités singulières. Aussi l’information et la cartographie de cette "couche manquante" permettent dès lors de questionner les réels tenants et aboutissants de la PSM en action, de mettre en perspective les enjeux qu’elle fait naître et d’ouvrir les horizons géographiquespour la mobilisation de cette autre réalité géographique. En somme, l’information et la cartographie de cette "couche manquante" se trouvent être un des nombreux enjeux démocratiques de ce début de XXIe siècle.

Published
2018

149. TCV-Pyr, villégiature et thermalisme dans les Pyrénées, entre inventaire matériel et immatériel

Author

Heiniger-Castéret, Patricia, Identités, Territoires, Expressions, Mobilités (ITEM), Université de Pau et des Pays de l'Adour (UPPA), and Service Patrimoine, Région Pays de la Loire

Subjects
[SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, [SHS.HIST]Humanities and Social Sciences/History, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract

International audience

Published
2018

150. Effect of rearing practices on the abundance of protein biomarkers of tenderness and intramuscular fat content in the French Rouge des Prés cows

Author

Picard, Brigitte, GAGAOUA, Mohammed, Bonnet, Muriel, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), SICA Rouge des Prés, Région Pays de la Loire, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, ProdInra, Migration, and Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [SHS] Humanities and Social Sciences, [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract

National audience

Published
2018

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