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1. A three-source SVAT modeling of evaporation : application to the seasonal dynamics of a grassed vineyard

Author

Frédéric Jacob, Jérôme Demarty, Carlo Montes, Jean-Paul Lhomme, Laurent Prévot, Laboratoire d'étude des Interactions Sol - Agrosystème - Hydrosystème (UMR LISAH), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), 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), Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), French Centre National d'Etudes Spatiales (CNES/TOSCA), European Commission's Seventh Framework Programme (FP7) through the 'Research Infrastructures' action under ExpeER project [262060], CONICYT-Chile for the doctoral grant / French Centre National d'Etudes Spatiales (CNES/TOSCA) and by the European Commission's Seventh Framework Programme (FP7/2007-2013), and Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Atmospheric Science, 010504 meteorology & atmospheric sciences, 0207 environmental engineering, Energy balance, Eddy covariance, 02 engineering and technology, 01 natural sciences, Vineyard, Sparse vegetation, Water balance, Seasonal course, Latent heat, [SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology, 020701 environmental engineering, Water content, Soil water balance, 0105 earth and related environmental sciences, 2. Zero hunger, Hydrology, Global and Planetary Change, Forestry, 15. Life on land, Latent heat flux, Multi-source, Soil water, Environmental science, Surface runoff, Agronomy and Crop Science
Abstract

International audience; A parsimonious and versatile Soil-Vegetation-Atmosphere Transfer (SVAT) model is proposed for three component vineyards, which includes vine foliage, grassed soil and bare soil. A three-source energy balance approach describes the energy and mass transfer between the soil-plant continuum and the lower atmosphere with an hourly time step. It is coupled with a soil water balance module running with a daily time step. The model makes use of standard meteorological data together with parameters describing foliage development, grass and soil characteristics. The model is calibrated by means of the Multi-objective Calibration Iterative Process (MCIP) algorithm and next validated for evaporation and soil moisture over a dataset collected in a Southern France grassed vineyard. The validation exercise is twofold. It focuses first on the daily course of evaporation derived from the surface energy balance module only, forced with meteorological variables, net radiation and soil moisture. The comparison against Eddy Covariance measurements shows a good agreement (R-2 = 0.96 and RMSE = 14.0 W m(-2)). Next, a simulation coupling the surface energy balance module with the soil water balance module is validated over Eddy Covariance and soil moisture measurements. Simulations throughout two contrasting growing seasons provide good estimates of daily evaporation (R-2 = 0.90 and RMSE = 0.43 mm d(-1)) and soil water content (R-2 =0.98 and RMSE = 6.95 mm). Model inaccuracies arise mainly under conditions of strong surface runoff. Results also suggest that the parameterizations relating the surface-atmosphere module with the soil module (i.e. stomatal resistance) should be carefully examined under water stress conditions. Finally, the model versatility is addressed through a set of simulations. It appears that the modeling approach allows assessing the seasonal water balance of vineyards with different structure (grass fraction or distance between rows) and that it could be applied to similar cropping systems.

Published
2014

2. Calcium activates purified human TRPA1 with and without its N-terminal ankyrin repeat domain in the absence of calmodulin

Author

Peter M. Zygmunt, Satish Babu Moparthi, Lavanya Moparthi, Jérôme Wenger, Linköping University (LIU), Biochimie membranaire et transport / Membrane Biochemistry and Transport, Institut Pasteur [Paris], Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Lund University [Lund], This study was supported by the Swedish Research Council (2014-3801) and the Medical Faculty of Lund University - ALF (Dnr. ALFSKANE-451751). This project has received funding from the Agence Nationale de la Recherche (ANR) under grant agreement ANR-17-CE09-0026-01 and from the European Research Council (ERC) under the European Commission’s Seventh Framework Programme (grant agreement 278242)., ANR-17-CE09-0026,AntennaFRET,Nanoantennes optiques pour exalter le transfert d'énergie de Förster : applications aux protéines(2017), European Project: 278242,EC:FP7:ERC,ERC-2011-StG_20101014,EXTENDFRET(2012), Institut Pasteur [Paris] (IP), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Calmodulin, Physiology, chemistry.chemical_element, Pain, Calcium, TRPA1, TRP channel, Transient receptor potential channel, 03 medical and health sciences, 0302 clinical medicine, Extracellular, Fluorescence Resonance Energy Transfer, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Binding site, Molecular Biology, TRPA1 Cation Channel, 030304 developmental biology, 0303 health sciences, biology, Bilayer, Biochemistry and Molecular Biology, food and beverages, Cell Biology, Ankyrin Repeat, 030104 developmental biology, Förster resonance energy transfer, chemistry, biology.protein, Biophysics, Ankyrin repeat, Ion Channel Gating, 030217 neurology & neurosurgery, Intracellular, Biokemi och molekylärbiologi
Abstract

Extracellular influx of calcium or release of calcium from intracellular stores have been shown to activate mammalian TRPA1 as well as to sensitize and desensitize TRPA1 electrophilic activation. Calcium binding sites on both intracellular N- and C-termini have been proposed. Here, we demonstrate based on Forster resonance energy transfer (FRET) and bilayer patch-clamp studies, a direct calmodulin-independent action of calcium on the purified human TRPA1 (hTRPA1), causing structural changes and activation without immediate subsequent desensitization of hTRPA1 with and without its N-terminal ankyrin repeat domain (N-ARD). Thus, calcium alone activates hTRPA1 by a direct interaction with binding sites outside the N-ARD. Funding Agencies|Swedish Research CouncilSwedish Research Council [2014-3801]; Medical Faculty of Lund University - ALF [ALFSKANE-451751]; Agence Nationale de la Recherche (ANR)French National Research Agency (ANR) [ANR-17-CE09-0026-01]; European Research Council (ERC) under the European Commissions Seventh Framework Programme [278242]

Published
2020
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3. Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 1: Fluxes and budgets of carbon, nitrogen and greenhouse gases from ecosystem monitoring and modelling

Author

Sutton, M.A., Flechard, C.R., Ibrom, A., Skiba, U.M., De Vries, W., Van Oijen, M., Cameron, D.R., DIse, N.B., Korhonen, J.F.J., Buchmann, N., Legout, A., Simpson, D., Sanz, M.J., Aubinet, M., Loustau, D., Montagnani, L., Neirynck, J., Janssens, I.A., Pihlatie, M., Kiese, R., European Commission, ABBA COST, Academy of Sciences, Atmospheric Environment Expert Ltd., CNR-ISAFOM, ECLAIRE, Geosciences and Environmental research, IGE, INRAE, Institute for Agriculture and Forestry Systems in the Mediterranean, Netherlands 31Institut National de la Recherche en Agriculture, Alimentation et Environnement, NitroEurope Integrated Project, UK Natural Environment Research Council, IRD, Université Grenoble Alpes, CNRS, and European Commission’s Seventh Framework Programme

Subjects
Europe, ecosystem modeling, greenhouse gas, vegetation type, organic nitrogen, environmental modeling, soil-vegetation interaction, forest ecosystem, carbon sequestration
Abstract

The impact of atmospheric reactive nitrogen (Nr) deposition on carbon (C) sequestration in soils and biomass of unfertilized, natural, semi-natural and forest ecosystems has been much debated. Many previous results of this dC∕dN response were based on changes in carbon stocks from periodical soil and ecosystem inventories, associated with estimates of Nr deposition obtained from large-scale chemical transport models. This study and a companion paper (Flechard et al., 2020) strive to reduce uncertainties of N effects on C sequestration by linking multi-annual gross and net ecosystem productivity estimates from 40 eddy covariance flux towers across Europe to local measurement-based estimates of dry and wet Nr deposition from a dedicated collocated monitoring network. To identify possible ecological drivers and processes affecting the interplay between C and Nr inputs and losses, these data were also combined with in situ flux measurements of NO, N2O and CH4 fluxes; soil NO−3 leaching sampling; and results of soil incubation experiments for N and greenhouse gas (GHG) emissions, as well as surveys of available data from online databases and from the literature, together with forest ecosystem (BASFOR) modelling. Multi-year averages of net ecosystem productivity (NEP) in forests ranged from −70 to 826 g C m−2 yr−1 at total wet + dry inorganic Nr deposition rates (Ndep) of 0.3 to 4.3 g N m−2 yr−1 and from −4 to 361 g C m−2 yr−1 at Ndep rates of 0.1 to 3.1 g N m−2 yr−1 in short semi-natural vegetation (moorlands, wetlands and unfertilized extensively managed grasslands). The GHG budgets of the forests were strongly dominated by CO2 exchange, while CH4 and N2O exchange comprised a larger proportion of the GHG balance in short semi-natural vegetation. Uncertainties in elemental budgets were much larger for nitrogen than carbon, especially at sites with elevated Ndep where Nr leaching losses were also very large, and compounded by the lack of reliable data on organic nitrogen and N2 losses by denitrification. Nitrogen losses in the form of NO, N2O and especially NO−3 were on average 27 % (range 6 %–54 %) of Ndep at sites with Ndep 3 g N m−2 yr−1. Such large levels of Nr loss likely indicate that different stages of N saturation occurred at a number of sites. The joint analysis of the C and N budgets provided further hints that N saturation could be detected in altered patterns of forest growth. Net ecosystem productivity increased with Nr deposition up to 2–2.5 g N m−2 yr−1, with large scatter associated with a wide range in carbon sequestration efficiency (CSE, defined as the NEP ∕ GPP ratio). At elevated Ndep levels (> 2.5 g N m−2 yr−1), where inorganic Nr losses were also increasingly large, NEP levelled off and then decreased. The apparent increase in NEP at low to intermediate Ndep levels was partly the result of geographical cross-correlations between Ndep and climate, indicating that the actual mean dC∕dN response at individual sites was significantly lower than would be suggested by a simple, straightforward regression of NEP vs. Ndep. Financial support. This research has been supported by the Acknowledgements. The authors gratefully acknowledge financial support by the European Commission through the two FP6 integrated projects CarboEurope Integrated Project (project no. GOCE-CT-2003-505572) and NitroEurope Integrated Project (project no. 017841), the FP7 ECLAIRE project (grant agreement no. 282910), and the ABBA COST Action ES0804. We are also thankful for funding from the French GIP-ECOFOR consortium under the F-ORE-T forest observation and experimentation network, as well as from the MDM-2017-0714 Spanish grant. We are grateful to Christian Bernhofer, Robert Clement, Han Dolman, Axel Don, Eric Dufrêne, Damiano Gianelle, Ruediger Grote, Anders Lindroth, John Moncrieff, Dario Papale, Corinna Rebmann and Alex Vermeulen for the data they provided, as well as to Klau-dia Ziemblińska for her comments on the paper. Computer time for EMEP model runs was supported by the Research Council of Norway through the NOTUR project EMEP (NN2890K). Finalization of the paper was supported by the UK Natural Environment Research Council award number NE/R016429/1 as part of the UK-SCAPE programme delivering national capability. We also wish to thank two anonymous referees for their constructive criticism of the paper.

Published
2020

4. The small subunit of Hemilipin2, a new heterodimeric phospholipase A2 from Hemiscorpius lepturus scorpion venom, mediates the antiangiogenic effect of the whole protein

Author

Lamia Borchani, Ivana Catacchio, Antonio Giovanni Solimando, Hafed Majdoub, Imen Jridi, Maria Antonia Frassanito, Delavar Shahbazzadeh, Angelo Vacca, Mohamed El Ayeb, Domenico Ribatti, Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), University of Bari Aldo Moro (UNIBA), Faculté des Sciences de Sfax, Université de Sfax - University of Sfax, Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), This work has been financially supported by the Tunisian Ministry of Research and Technology (MERST), and by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Investigator Grant (no. 14095 to AV), Special Program Molecular Clinical Oncology 5 per 1000 (no. 9965 to AV), Milan, IT, and the European Commission's Seventh Framework Programme (EU FPT7) OVER-MyR (no. 278706 to AV)., and We gratefully thank Professor Hechmi Louzir, Head of Pateur Institute of Tunis and Professor Mohamed Samir Boubaker Head of the Laboratoire d' Anathomopathologie, Pasteur Institute of Tunis for their continuous interest and their support during this work. We also thank Daniel Lafitte and Claude Villard (INSERM UMR 911-CRO2 Faculty of Pharmacy Marseille, France) for their technical assistance in mass spectrometry.

Subjects
0301 basic medicine, Hemiscorpius lepturus sPLA2 group III, MESH: Phospholipases A2/chemistry, Angiogenesis, MESH: Angiogenesis Inhibitors/isolation & purification, Angiogenesis Inhibitors, Chick Embryo, Toxicology, Chorioallantoic Membrane, HUVEC, Small subunit, MESH: Animals, MESH: Angiogenesis Inhibitors/pharmacology, MESH: Human Umbilical Vein Endothelial Cells, Tube formation, biology, HPAEC, MESH: Protein Subunits/pharmacology, MESH: Chick Embryo, MESH: Protein Subunits/physiology, Chorioallantoic membrane, Biochemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, MESH: Scorpion Venoms/chemistry, MESH: Phospholipases A2/isolation & purification, Protein subunit, Scorpion Venoms, Cell Line, 03 medical and health sciences, Phospholipase A2, MESH: Cell Adhesion/drug effects, In vivo, MESH: Angiogenesis Inhibitors/chemistry, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Acetophenones/chemistry, MESH: Humans, 030102 biochemistry & molecular biology, Edman degradation, Acetophenones, MESH: Phospholipases A2/pharmacology, Molecular biology, In vitro, MESH: Cell Line, Phospholipases A2, Protein Subunits, 030104 developmental biology, MESH: Protein Subunits/chemistry, biology.protein, MESH: Chorioallantoic Membrane/drug effects
Abstract

International audience; In a previous study, we reported the identification of Hemilipin, the first secreted heterodimeric phospholipase A2 (sPLA2) from Hemiscorpius lepturus scorpion venom and demonstrated its effective inhibition of all angiogenesis key steps in vitro and in vivo. Here, we aimed to characterize a second sPLA2, Hemilipin2, from the same venom and to elucidate its antiangiogenic effect. The protein was purified by chromatography separation and analyzed by MALDI/TOF mass spectrometry. Its N terminal amino acid sequence was determined by Edman degradation method and the enzymatic activity by fatty acids release assay. Hemilipin2 antiangiogenic activity was investigated by studying its effect in vitro on adhesion, migration and capillary like tube formation of Human Umbilical Vein Endothelial Cells (HUVECs) and Human Pulmonary Artery Endothelial Cells (HPAECs); and in vivo on the chick embryo chorioallantoic membrane (CAM) assay. Data to be presented show that Hemilipin2 is heterodimeric composed by two subunits: the large one has a molecular weight of 12,866 and the small one of 2461 a.m.u. It has a strong calcium-dependent PLA2 activity and impacts angiogenesis in vitro and in vivo without showing any cytotoxic or apoptotic signs. Its chemical modification with p-Bromophenacyl Bromide abolishes the enzymatic activity without affecting the antiangiogenic effect. Furthermore, it has been proved that Hemilipin2 small subunit was able to inhibit blood vessel formation both in vitro and in vivo. These findings may serve as a starting point for the designing of a new generation of specific inhibitor of human angiogenesis at different steps. (C) 2016 Elsevier Ltd. All rights reserved.

Published
2017

5. Charge migration in photo-ionized aromatic amino acids

Author

Trabattoni A., Galli M., Lara-Astiaso M., Palacios A., Greenwood J., Tavernelli I., Decleva P., Nisoli M., Martín F., Calegari F. and Data accessibility. This article has no additional data. Authors’ contributions. A.T., M.G., A.P., F.M. and F.C. drafted the manuscript. M.L.-A., J.G., I.T., P.D. and M.N. helped draft the manuscript. All authors gave final approval for publication. Competing interests. The authors declare that they have no competing interests. Funding. Work supported by the MINECO project FIS2016-77889-R, the European Research Council under the ERC starting grant no. 637756 STARLIGHT and LASERLAB-EUROPE (grant agreement no. 284464, European Commission’s Seventh Framework Programme). We acknowledge computer time from CCC-UAM and Marenostrum Supercomputer Center. F.M. acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686) and the ‘María de Maeztu’ Programme for Units of Excellence in R&D (MDM-2014-0377).

Published
2019

6. Two independent modes of chromatin organization revealed by cohesin removal

Author

Anton Goloborodko, Geoffrey Fudenberg, Nuno A. Fonseca, Nezar Abdennur, Christian H. Haering, François Spitz, Aleksandra Pekowska, Yann Loe-Mie, Leonid A. Mirny, Wolfgang Huber, Wibke Schwarzer, European Molecular Biology Laboratory [Heidelberg] (EMBL), Massachusetts Institute of Technology (MIT), Génomique et Epigénomique du Développement des Vertébrés - Genomics and Epigenomics of Vertebrates Development, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Department of Physics [MIT Cambridge], W.S. and A.P. were supported by an EMBL Interdisciplinary Postdoc (EIPOD) Fellowship under Marie Curie Actions COFUND. The work in the Mirny laboratory is supported by R01 GM114190, U54 DK107980 from the NIH, and 1504942 from the NSF. The collaboration is also partially supported by the MIT-France MISTI Fund. The work in the Spitz laboratory was supported by EMBL, the Pasteur Institute and the Deutsche Forschungsgesellschaft (DFG grant: SP 1331/3-1) and included funding from the European Commission’s Seventh Framework Programme through the Collaborative Research Project RADIANT (grant agreement no. 305626, to W.H.)., European Project: 305626,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,RADIANT(2012), Génomique et Epigénomique du Développement des Vertébrés - Genomics and Epigenomics of Vertebrate Development, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Transcription, Genetic, Chromosomal Proteins, Non-Histone, Cell Cycle Proteins, Biology, Genome, Article, Chromosomes, Epigenesis, Genetic, Chromosome conformation capture, 03 medical and health sciences, Mice, Humans, Animals, Epigenetics, Chromosome Positioning, Enhancer, Gene, Multidisciplinary, Cohesin, Computational Biology, Chromatin, Cell biology, 030104 developmental biology, Enhancer Elements, Genetic, Liver, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Transcription Factors
Abstract

International audience; Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.

Published
2017

7. Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Author

Miren Dorronsoro, Marc J. Gunter, Mathilde His, Helena Schock, Sabina Sieri, Maria Dolores Chirlaque, Aurélie Affret, Rudolf Kaaks, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Philippos Orfanos, Melissa A. Merritt, Anne Tjønneland, Domenico Palli, J. Ramón Quirós, María José Sánchez, Theron Johnson, Danja Sarink, Eva Ardanaz, Antonio Agudo, Renée T. Fortner, Laure Dossus, Timothy J. Key, Kim Overvad, Rosario Tumino, Androniki Naska, Petra H.M. Peeters, Heiner Boeing, Amalia Mattiello, Anja Olsen, Sabina Rinaldi, Eiliv Lund, Antonia Trichopoulou, Carla H. van Gils, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Elio Riboli, Fulvio Ricceri, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, University Medical Center Utrecht, Imperial College Trust, [Fortner,RT, Sarink,D, Schock,H, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Affret,A, His,M, Boutron-Ruault,MC] Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. [Affret,A, Boutron-Ruault,MC] Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.p.Arezzo' Hospital, ASP Ragusa, Italy. [Ricceri,F] Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy. [Ricceri,F] Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Peeters,PH, Van Gils,CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. [Weiderpass,E, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. [Weiderpass,E] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E] Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Research Institute CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Rinaldi,S, Dossus,L, Gunter,M] International Agency for Research on Cancer, Lyon, France., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain), the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).

Subjects
0301 basic medicine, Oncology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Estrogen receptor, Progesterone receptor, Cohort Studies, 0302 clinical medicine, Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B [Medical Subject Headings], Risk Factors, Prospective Studies, Prospective cohort study, Medicine(all), Osteoprotegerina, biology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 11 Medical And Health Sciences, General Medicine, Middle Aged, Necrosi, 3. Good health, European Prospective Investigation into Cancer and Nutrition, RANK axis, RANKL, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, Receptores estrogénicos, Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Receptores de hormonas, Hormone receptor, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Càncer de mama, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Necrosis, 03 medical and health sciences, Osteoprotegerin, General & Internal Medicine, Internal medicine, Journal Article, medicine, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Case-control study, medicine.disease, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], 030104 developmental biology, Endocrinology, Case-Control Studies, Nested case-control study, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause [Medical Subject Headings], biology.protein, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract

All Author: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli and Rudolf Kaaks, Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; ptrend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer diagnosis (phet ≥ 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).

Published
2017

8. PLATO as it is: a legacy mission for Galactic archaeology

Author

A. Miglio, C. Chiappini, B. Mosser, G. R. Davies, K. Freeman, L. Girardi, P. Jofré, D. Kawata, B. M. Rendle, M. Valentini, L. Casagrande, W. J. Chaplin, G. Gilmore, K. Hawkins, B. Holl, T. Appourchaux, K. Belkacem, D. Bossini, K. Brogaard, M.‐J. Goupil, J. Montalbán, A. Noels, F. Anders, T. Rodrigues, G. Piotto, D. Pollacco, H. Rauer, C. Allende Prieto, P. P. Avelino, C. Babusiaux, C. Barban, B. Barbuy, S. Basu, F. Baudin, O. Benomar, O. Bienaymé, J. Binney, J. Bland‐Hawthorn, A. Bressan, C. Cacciari, T. L. Campante, S. Cassisi, J. Christensen‐Dalsgaard, F. Combes, O. Creevey, M. S. Cunha, R. S. Jong, P. Laverny, S. Degl'Innocenti, S. Deheuvels, É. Depagne, J. Ridder, P. Di Matteo, M. P. Di Mauro, M.‐A. Dupret, P. Eggenberger, Y. Elsworth, B. Famaey, S. Feltzing, R. A. García, O. Gerhard, B. K. Gibson, L. Gizon, M. Haywood, R. Handberg, U. Heiter, S. Hekker, D. Huber, R. Ibata, D. Katz, S. D. Kawaler, H. Kjeldsen, D. W. Kurtz, N. Lagarde, Y. Lebreton, M. N. Lund, S. R. Majewski, P. Marigo, M. Martig, S. Mathur, I. Minchev, T. Morel, S. Ortolani, M. H. Pinsonneault, B. Plez, P. G. Prada Moroni, D. Pricopi, A. Recio‐Blanco, C. Reylé, A. Robin, I. W. Roxburgh, M. Salaris, B. X. Santiago, R. Schiavon, A. Serenelli, S. Sharma, V. Silva Aguirre, C. Soubiran, M. Steinmetz, D. Stello, K. G. Strassmeier, P. Ventura, R. Ventura, N. A. Walton, C. C. Worley, Institut d'Astrophysique et de Géophysique [Liège], Université de Liège, Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Arizona State University [Tempe] (ASU), Leibniz-Institut für Astrophysik Potsdam (AIP), Department of Physics and Astronomy [Aarhus], Aarhus University [Aarhus], School of Physics and Astronomy [Birmingham], University of Birmingham [Birmingham], Heckscher-Klinikum, Danish AsteroSeismology Centre (DASC), Universidade Federal de São Paulo (UNIFESP), DLR Institut für Planetenforschung, Deutsches Zentrum für Luft- und Raumfahrt [Berlin] (DLR), Department of Astronomy [New Haven], Yale University [New Haven], Evolution et Modélisation des Bassins Sédimentaires (EMBS), Institut des Sciences de la Terre de Paris (iSTeP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Department of Biomedical, Metabolic and Neural Sciences [Modena], Chaire Galaxies et cosmologie, Collège de France (CdF (institution)), Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Universidade de Aveiro, Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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)-Centre National de la Recherche Scientifique (CNRS), Las Cumbres Observatory (LCO), Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève (UNIGE), Université de Strasbourg (UNISTRA), Observatoire astronomique de Strasbourg (ObAS), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Universitat de Girona (UdG), Max-Planck-Institut für Extraterrestrische Physik (MPE), Max-Planck-Institut für Sonnensystemforschung (MPS), Max-Planck-Gesellschaft, SETI Institute, University of Illinois at Urbana Champaign (UIUC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, Universidade Federal de Santa Catarina = Federal University of Santa Catarina [Florianópolis] (UFSC), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Space Science Institute [Boulder] (SSI), Department of Astronomy (Ohio State University), Ohio State University [Columbus] (OSU), Laboratoire Univers et Particules de Montpellier (LUPM), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Astrophysical Research Institute [Liverpool], Liverpool John Moore University (ljmu), Institute of Space Sciences [Barcelona] (ICE-CSIC), Spanish National Research Council [Madrid] (CSIC), Sydney Institute for Astronomy (SIfA), The University of Sydney, M2A 2017, Laboratoire d'Astrophysique de Bordeaux [Pessac] (LAB), Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Leibniz Institute for Astrophysics Potsdam (AIP), Symbiose Marine (SM), Evolution Paris Seine, Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), DNRF106, The Danish National Research Foundation, Centre National d’Etudes Spatiales, PRIN INAF 2014 - CRA 1.05.01.94.05, Science and Technology Facilities Council, Programme National Cosmologie et Galaxies (CNRS/INSU, France), IF/00894/2012/, Federación Española de Enfermedades Raras, CNES Fellowship, 615604, ERC Consolidator (STARKEY), Federaal Wetenschapsbeleid, ESP2015-66134-R, Ministerio de Economía y Competitividad, European Commission's Seventh Framework Programme, Swedish National Space Board, European Commission, DLR, FT1400147, Australian Research Council, NNX16AI09G, National Aeronautics and Space Administration, European Cooperation in Science and Technology, CH1188/2-1, DFG, CA16117, ChETEC COST Action, 10118, Villum Fonden, European Union FP7 program, 320360, ERC, UID/FIS/04434/2013, FCT, G1502, NYUAD Institute, Programme National de Physique Stellaire (PNPS), ITA, USA, GBR, FRA, DEU, ESP, Federal University of Sao Paulo (Unifesp), Université Paris-Saclay, Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Collège de France - Chaire Galaxies et cosmologie, Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), 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), Université de Genève = University of Geneva (UNIGE), Max-Planck-Institut für Sonnensystemforschung = Max Planck Institute for Solar System Research (MPS), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, University of Illinois System, Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Miglio A., Chiappini C., Mosser B., Davies G.R., Freeman K., Girardi L., Jofre P., Kawata D., Rendle B.M., Valentini M., Casagrande L., Chaplin W.J., Gilmore G., Hawkins K., Holl B., Appourchaux T., Belkacem K., Bossini D., Brogaard K., Goupil M.-J., Montalban J., Noels A., Anders F., Rodrigues T., Piotto G., Pollacco D., Rauer H., Prieto C.A., Avelino P.P., Babusiaux C., Barban C., Barbuy B., Basu S., Baudin F., Benomar O., Bienayme O., Binney J., Bland-Hawthorn J., Bressan A., Cacciari C., Campante T.L., Cassisi S., Christensen-Dalsgaard J., Combes F., Creevey O., Cunha M.S., Jong R.S., Laverny P., Degl'Innocenti S., Deheuvels S., Depagne E., Ridder J., Matteo P.D., Mauro M.P.D., Dupret M.-A., Eggenberger P., Elsworth Y., Famaey B., Feltzing S., Garcia R.A., Gerhard O., Gibson B.K., Gizon L., Haywood M., Handberg R., Heiter U., Hekker S., Huber D., Ibata R., Katz D., Kawaler S.D., Kjeldsen H., Kurtz D.W., Lagarde N., Lebreton Y., Lund M.N., Majewski S.R., Marigo P., Martig M., Mathur S., Minchev I., Morel T., Ortolani S., Pinsonneault M.H., Plez B., Moroni P.G.P., Pricopi D., Recio-Blanco A., Reyle C., Robin A., Roxburgh I.W., Salaris M., Santiago B.X., Schiavon R., Serenelli A., Sharma S., Aguirre V.S., Soubiran C., Steinmetz M., Stello D., Strassmeier K.G., Ventura P., Ventura R., Walton N.A., Worley C.C., Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Montpellier 2 - Sciences et Techniques (UM2), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
RED-GIANT STARS, Astrophysics, 01 natural sciences, COROT ASTEROSEISMOLOGY FIELDS, Astrophysics::Solar and Stellar Astrophysics, VELOCITY EXPERIMENT RAVE, Galaxy: structure, 010303 astronomy & astrophysics, SUN-LIKE STAR, QC, QB, Physics, structure - stars: abundances - stars: fundamental parameters - stars: oscillations - surveys [Galaxy], Astrophysics - Solar and Stellar Astrophysics, stars: fundamental parameters, stars: oscillations, Astrophysics::Earth and Planetary Astrophysics, SOLAR-LIKE OSCILLATIONS, THICK DISK, stars: abundances, Relation (database), DATA RELEASE, Milky Way, surveys, Astronomy and Astrophysics, Space and Planetary Science, FOS: Physical sciences, MILKY-WAY DISK, F500, Kepler, Asteroseismology, ATMOSPHERIC PARAMETERS, Settore FIS/05 - Astronomia e Astrofisica, 0103 physical sciences, Quality (philosophy), Galaxy: structure â stars: abundances â stars: fundamental parameters â stars: oscillations â surveys, Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics, 010308 nuclear & particles physics, Galaxy: structure – stars: abundances – stars: fundamental parameters – stars: oscillations – surveys, [PHYS.ASTR.SR]Physics [physics]/Astrophysics [astro-ph]/Solar and Stellar Astrophysics [astro-ph.SR], Data science, Astrophysics - Astrophysics of Galaxies, Galaxy, COLD DARK-MATTER, Stars, Astrophysics of Galaxies (astro-ph.GA), Stellar physics, Galaxy: structure – stars: abundances – stars: fundamental parameters – stars: oscillations – surveys, Galaxy: structure - stars: abundances - stars: fundamental parameters - stars: oscillations - surveys
Abstract

Deciphering the assembly history of the Milky Way is a formidable task, which becomes possible only if one can produce high-resolution chrono-chemo-kinematical maps of the Galaxy. Data from large-scale astrometric and spectroscopic surveys will soon provide us with a well-defined view of the current chemo-kinematical structure of the Milky Way, but will only enable a blurred view on the temporal sequence that led to the present-day Galaxy. As demonstrated by the (ongoing) exploitation of data from the pioneering photometric missions CoRoT, Kepler, and K2, asteroseismology provides the way forward: solar-like oscillating giants are excellent evolutionary clocks thanks to the availability of seismic constraints on their mass and to the tight age-initial-mass relation they adhere to. In this paper we identify five key outstanding questions relating to the formation and evolution of the Milky Way that will need precise and accurate ages for large samples of stars to be addressed, and we identify the requirements in terms of number of targets and the precision on the stellar properties that are needed to tackle such questions. By quantifying the asteroseismic yields expected from PLATO for red-giant stars, we demonstrate that these requirements are within the capabilities of the current instrument design, provided that observations are sufficiently long to identify the evolutionary state and allow robust and precise determination of acoustic-mode frequencies. This will allow us to harvest data of sufficient quality to reach a 10% precision in age. This is a fundamental pre-requisite to then reach the more ambitious goal of a similar level of accuracy, which will only be possible if we have to hand a careful appraisal of systematic uncertainties on age deriving from our limited understanding of stellar physics, a goal which conveniently falls within the main aims of PLATO's core science., 17 pages, 9 figures, accepted for publication in Astronomical Notes

Published
2017

9. Plasmonic Nanoantennas Enable Forbidden Förster Dipole–Dipole Energy Transfer and Enhance the FRET Efficiency

Author

Mathieu Mivelle, Jérôme Wenger, Hervé Rigneault, Maria F. Garcia-Parajo, Emmanuel Margeat, Satish Babu Moparthi, Niek F. van Hulst, Juan de Torres, MOSAIC (MOSAIC), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), The research leading to these results has received funding fromthe European Commission’s Seventh Framework Programme(FP7-ICT-2011-7) under grant agreements ERC StG 278242(ExtendFRET), 288263 (NanoVista), and ERC AdG 247330(Nano Antennas)., European Project: 278242,EC:FP7:ERC,ERC-2011-StG_20101014,EXTENDFRET(2012), European Project: 288263,EC:FP7:ICT,FP7-ICT-2011-7,NANO-VISTA(2011), European Project: 247330,EC:FP7:ERC,ERC-2009-AdG,NANOANTENNAS(2010), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Materials science, Organic solar cell, Energy transfer, New energy, Physics::Optics, Bioengineering, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Quantitative Biology::Subcellular Processes, LDOS, Nanoruler, General Materials Science, Fluorescence enhancement, Plasmon, [PHYS]Physics [physics], Quantitative Biology::Biomolecules, Physics::Biological Physics, business.industry, Dipole−dipole interaction, Mechanical Engineering, Optical antenna, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Acceptor, 0104 chemical sciences, Dipole, Förster resonance energy transfer, FRET, Optoelectronics, Plasmonics, 0210 nano-technology, business
Abstract

International audience; Förster resonance energy transfer (FRET) plays a key role in biochemistry, organic photovoltaics, and lighting sources. FRET is commonly used as a nanoruler for the short (nanometer) distance between donor and acceptor dyes, yet FRET is equally sensitive to the mutual dipole orientation. The orientation dependence complicates the FRET analysis in biological samples and may even lead to the absence of FRET for perpendicularly oriented donor and acceptor dipoles. Here, we exploit the strongly inhomogeneous and localized fields in plasmonic nanoantennas to open new energy transfer routes, overcoming the limitations from the mutual dipole orientation to ultimately enhance the FRET efficiency. We demonstrate that the simultaneous presence of perpendicular near-field components in the nanoantenna sets favorable energy transfer routes that increase the FRET efficiency up to 50% for nearly perpendicular donor and acceptor dipoles. This new facet of plasmonic nanoantennas enables dipole–dipole energy transfer that would otherwise be forbidden in a homogeneous environment. As such, our approach further increases the applicability of single-molecule FRET over diffraction-limited approaches, with the additional benefits of higher sensitivities and higher concentration ranges toward physiological levels.

Published
2016

10. Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia

Author

Harr Freeya Njai, Ramou Njie, Ousman Nyan, Christian Bottomley, Maud Lemoine, Gibril Ndow, Yusuke Shimakawa, Lamin Bojang, Umberto D'Alessandro, Andrew J. Hall, Mark Thursz, Makie Taal, Abdoulie Jatta, Saydiba Tamba, Department of Infectious Disease Epidemiology [London] (IDE), Faculty of Epidemiology and Population Health [London], London School of Hygiene and Tropical Medicine (LSHTM)-London School of Hygiene and Tropical Medicine (LSHTM), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Medical Research Council Unit The Gambia (MRC), Imperial College London, Ministry of Health and Social Welfare [Banjul, The Gambia] (MOHSW), Edward Francis Small Teaching Hospital [Banjul, Gambia] (EFSTH), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), This work was supported by the European Commission's Seventh Framework Programme (grant 265994, PROLIFICA)., The authors thank MRC Unit, The Gambia, the Gambia National Cancer Registry, the Gambia Government and the Imperial College London which supported the study. The authors also thank Dr Debbie Garside and Prof Simon‐Taylor Robinson at the Imperial College London, Dr Abubacarr Kambi, Dr Louise Sarr, Mr Famara Bojang, Ms Deboh Jallow, Mr Sheriff Koley, Ms Yamundow‐Jallow Samba, Mr Alagie Sanneh, Mr Demba Sonko and Ms Mavis Foster‐Nyarko at MRC Unit, The Gambia., European Project: 265994,EC:FP7:HEALTH,FP7-AFRICA-2010,PROLIFICA(2011), and Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)

Subjects
Male, HBsAg, MESH: Logistic Models, carcinoma, medicine.disease_cause, MESH: Aged, 80 and over, MESH: Pregnancy, Pregnancy, Risk Factors, MESH: Risk Factors, Medicine, 2. Zero hunger, Aged, 80 and over, MESH: Aged, education.field_of_study, MESH: Middle Aged, Obstetrics, MESH: Birth Order, Liver Neoplasms, MESH: Carrier State / virology, Hepatitis B, Middle Aged, MESH: Case-Control Studies, MESH: Infant, 3. Good health, MESH: Infectious Disease Transmission, Vertical, Birth order, MESH: Hepatitis B virus, Hepatocellular carcinoma, Carrier State, Female, Gambia, Adult, medicine.medical_specialty, Hepatitis B virus, Carcinoma, Hepatocellular, MESH: Hepatitis B Surface Antigens / genetics, MESH: Gambia / epidemiology, Population, MESH: Hepatitis B, Chronic / epidemiology, Hepatitis B, Chronic, hepatocellular, vertical, MESH: Hepatitis B Vaccines / therapeutic use, Humans, MESH: Carrier State / epidemiology, Hepatitis B Vaccines, MESH: Carcinoma, Hepatocellular / epidemiology, education, birth order, Aged, Hepatitis B Surface Antigens, MESH: Humans, Hepatology, business.industry, MESH: Liver Neoplasms / epidemiology, MESH: Hepatitis B, Chronic / transmission, Case-control study, Infant, MESH: Adult, Odds ratio, infectious disease transmission, medicine.disease, Infectious Disease Transmission, Vertical, digestive system diseases, MESH: Male, Logistic Models, Case-Control Studies, Immunology, Africa, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract

International audience; Background & aims: Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity.Methods: The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63).Results: HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04).Conclusions: Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia.

Published
2015

11. LACCASE5 Is Required for Lignification of the Brachypodium distachyon Culm

Author

Oumaya Bouchabke-Coussa, Camille Soulhat, Grégory Mouille, Catherine Lapierre, Halima Morin, Frédéric Legée, Sébastien Antelme, Yin Wang, Laurent Cézard, Marion Dalmais, Philippe Lebris, Emilie Gineau, Abdelafid Bendahmane, Richard Sibout, Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, unité mixte CNRS, Centre National de la Recherche Scientifique (CNRS), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique program Amelioration de la Ligno-Cellulose, European Commission’s Seventh Framework Programme project RENEWALL (grant no. 211982), the Knowledge-Based Bio Economy project CELLWALL, and BRAVO (grant no. ANR–14–CE19–0012–01), China Scholarship Council, ANR-14-CE19-0012,BRAVO,Ontogénie des tissus vasculaires chez les graminées(2014), Unité de recherche en génomique végétale (URGV), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Université d'Évry-Val-d'Essonne (UEVE), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
2. Zero hunger, Laccase, Messenger RNA, biology, Physiology, [SDV]Life Sciences [q-bio], Mutant, food and beverages, Plant Science, biology.organism_classification, Ferulic acid, chemistry.chemical_compound, Hydrolysis, Biochemistry, chemistry, Botany, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Genetics, biology.protein, Lignin, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Brachypodium distachyon, Peroxidase
Abstract

The oxidation of monolignols is a required step for lignin polymerization and deposition in cell walls. In dicots, both peroxidases and laccases are known to participate in this process. Here, we provide evidence that laccases are also involved in the lignification of Brachypodium distachyon, a model plant for temperate grasses. Transcript quantification data as well as in situ and immunolocalization experiments demonstrated that at least two laccases (LACCASE5 and LACCASE6) are present in lignifying tissues. A mutant with a misspliced LACCASE5 messenger RNA was identified in a targeting-induced local lesion in genome mutant collection. This mutant shows 10% decreased Klason lignin content and modification of the syringyl-to-guaiacyl units ratio. The amount of ferulic acid units ester linked to the mutant cell walls is increased by 40% when compared with control plants, while the amount of ferulic acid units ether linked to lignins is decreased. In addition, the mutant shows a higher saccharification efficiency. These results provide clear evidence that laccases are required for B. distachyon lignification and are promising targets to alleviate the recalcitrance of grass lignocelluloses.

Published
2015

12. Deposit of microbial strains in public service collections as part of the publication process to underpin good practice in science

Author

Giovanna Cristina Varese, P.D. Bridge, Serge Casaregola, Nelson Lima, David Smith, Erko Stackebrandt, Gerard Verkleij, Stackebrandt, Erko, Universidade do Minho, Microbial Ressource Research Infrastructure, Partenaires INRAE, Centre for Agricultural and Biosciences International (CABI), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Universita di Torino, CBS-KNAW Fungal Biodiversity Centre, European Commission's Seventh Framework Programme (FP7), Research Infrastructures action [FP7-228310], European Union's Seventh Framework Programme for Research, Technological Development and Demonstration [312251], and Westerdijk Fungal Biodiversity Institute

Subjects
Deposition policy, 0303 health sciences, Multidisciplinary, Science & Technology, Operations research, 030306 microbiology, business.industry, [SDV]Life Sciences [q-bio], education, Deposition 'key' criteria, Short Report, Public relations, 03 medical and health sciences, Biological resource centres, Deposition ‘key’ criteria, Credibility of science, Medicine, Public service, business, Good practice, Publication process, 030304 developmental biology, Public resource
Abstract

Despite recommendations to release microbial resources to the community post-publication, the reality is far from satisfying. A workshop discussed the need for a coordinated and effective deposition policy for 'key' microbial strains and proposes a set of criteria to facilitate their deposition into public service collections. The majority of authors either contacted directly or during submission of manuscripts to several international, mainly European bacteriology journals agreed to this set of 'key strain' criteria and to the voluntarily deposition of resources into public resource centres., The authors thank additional members of the 2011 Braunschweig workshop: Jorg Overmann, Esperanza Garay-Auban, Peter Kampfer, Yohan Lecuona, James I Prosser, Ramon Rosello-Mora, Karl-Heinz Schleifer, and Kornelia Smalla. The workshop was an initiative of the European Consortium of Microbial Resource Centres (EMbaRC), supported by the European Commission's Seventh Framework Programme (FP7, 2007-2013), Research Infrastructures action, under the grant agreement No. FP7-228310. This communication received funding from the European Union's Seventh Framework Programme for Research, Technological Development and Demonstration under grant agreement no 312251. Additionally, thanks go to all those attending the February 2014 MIRRI Heads of Collections meeting who participated in the discussions, including some of those above plus Pedro Crous, Edward Moore, Oleg Stupar, Chantal Bizet, Dominique Clermont, Rosa Aznar, Paul Devos, and Anna Misiewicz.

Published
2014

13. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension

Author

Hang N Nielsen, Urs D Lichtenauer, Elisabeth Graf, Sheerazed Boulkroun, Thomas Meitinger, Felix Beuschlein, Pierre-François Plouin, Laurence Amar, Vivien Rodacker Schack, Francesco Fallo, Susanne Diener, Bruno Allolio, Tim M. Strom, Paolo Mulatero, Evelyn Fischer, Philipp Tauber, David Penton, Benoit Samson-Couterie, Anett Walther, Martin Reincke, Arndt Benecke, Thomas Wieland, Bente Vilsen, Franco Mantero, Marcus Quinkler, Maria-Christina Zennaro, Richard Warth, Xavier Jeunemaitre, Andrea Osswald, Thomas Schwarzmayr, Expression des Gènes et comportement adaptatifs = Molecular Genetics, Neurophysiology and Behavior (NPS-15), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Else Kroner-Fresenius-Stiftung, German Conn's Registry-Else-Kroner Hyperaldosteronism Registry, Agence Nationale pour la Recherche, ANR Physio [013-01], Genopat [08-GEN0-021], Fondation pour la Recherche sur l'Hypertension Arterielle [AO 2007], Fondation pour la Recherche Medicate [ING20101221177], Programme Hospitalier de Recherche Clinique, PHRC [AOM 06179], Danish Medical Research Council, Novo Nordisk Foundation, Lundbeck Foundation, Deutsche Forschungsgemeinschaft [Re 752/17-1, FOR1086], Fondi Ricerca Ex-60% MIUR (Ministry of University, Scientific and Technological Research), German Ministry of Education and Research [01GR0802, 01GM0867], European Commission's Seventh Framework Programme [261123], GEUVADIS, DZHK Paris, INSERM [U982], University Hospital of Rouen, INSERM, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Familial hyperaldosteronism, ATPase, 030209 endocrinology & metabolism, Biology, Immunoenzyme Techniques, Plasma Membrane Calcium-Transporting ATPases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Primary aldosteronism, Internal medicine, KCNJ5, Genetics, medicine, Humans, Adrenal adenoma, Aldosterone, Cells, Cultured, 030304 developmental biology, 0303 health sciences, primary aldosteronism, ATPase Gene, Sodium, Conn's syndrom, medicine.disease, Adrenal Cortex Neoplasms, Electrophysiology, Endocrinology, adrenal, chemistry, Na,K-ATPase, Adrenocortical Adenoma, Hypertension, Mutation, Calcium ion homeostasis, Potassium, biology.protein, Calcium, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sodium-Potassium-Exchanging ATPase
Abstract

Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na+/K+ ATPase α subunit) and ATP2B3 (encoding a Ca2+ ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations and lower potassium concentrations compared with mutation-negative cases. In summary, dominant somatic alterations in two members of the ATPase gene family result in autonomous aldosterone secretion. Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na(+)/K(+) ATPase α subunit) and ATP2B3 (encoding a Ca(2+) ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16 (5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations and lower potassium concentrations compared with mutation-negative cases. In summary, dominant somatic alterations in two members of the ATPase gene family result in autonomous aldosterone secretion.

Published
2013

14. Draft Genome Sequence of [i][/i] Lactobacillus pasteurii[i][/i] CRBIP 24.76T

Author

Cousin, Sylvie, Clermont, Dominique, Creno, Sophie, Ma, Laurence, Loux, Valentin, Bizet, Chantal, Bouchier, Christiane, Centre de Ressources biologiques de l'Institut Pasteur - Biological Resource Center of the Institut Pasteur (CRBIP), Institut Pasteur [Paris], Génomique (Plate-Forme) - Genomics Platform, Unité Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), This communication is an initiative of the European Consortium of Microbial Resources Centres (EMbaRC), supported by the European Commission’s Seventh Framework Programme (FP7, 2007–2013), Research Infrastructures action, under the grant agreement no. FP7-228310., European Project: 228310,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2008-1,EMBARC(2009), Centre de Ressources biologiques de l'Institut Pasteur (CRBIP), Génomique (Plate-Forme), Institut Pasteur [Paris] (IP), and Unité Mathématique Informatique et Génome (MIG)

Subjects
[SDV]Life Sciences [q-bio], food and beverages
Abstract

We report the draft genome sequence of the type strain Lactobacillus pasteurii CRBIP 24.76, which is closely related to L. gigeriorum CRBIP 24.85(T), isolated from a chicken crop. The total length of the 29 contigs is about 1.9 Mb, with a G+C content of 40% and 1,946 coding sequences.

Published
2013

15. Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors

Author

Guanghua Yang, Pascale Bouillé, Karim Si-Tayeb, Noushin Dianat, Clémence Martinet, Ludovic Vallier, Rémi Vernet, Denis Clay, Sébastien Corbineau, Anne Weber, Deborah J. Burks, Régis Gayon, Anne Dubart-Kupperschmitt, Gérard Tachdjian, Sylvie Goulinet-Mainot, Les cellules souches : de leurs niches à leurs applications thérapeutiques, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vectalys SAS, Service d'histologie, embryologie et cytogénétique [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIBER de Diabetes y Obesidad, Centro de Investigación Principe Felipe, Department of Surgery, The Anne McLaren Laboratory for Regenerative Medicine, This study was supported by the European Commission's Seventh Framework Programme under grant agreements No. 223317 (LIV-ES) and No. 278152 (InnovaLiv), and grants from Région Ile de France Pôle de Compétitivité Médicen 'Ingecell', from Agence de la Biomédecine and from Ministry of Research (ANR, 2010-RFCS-004: Liv-iPS). KST was supported by the Fondation pour la Recherche Médicale (FRM), SC was supported by the Association Française contre les Myopathies (AFM), and ND was supported by the Région Ile de France (DIM-Stem Pôle)., European Project: 223317,EC:FP7:HEALTH,FP7-HEALTH-2007-B,LIV-ES(2008), BMC, Ed., and Development of culture conditions for the differentiation of hES cells into hepatocytes - LIV-ES - - EC:FP7:HEALTH2008-10-01 - 2012-03-31 - 223317 - VALID

Subjects
Physiology, Hepatoblasts, Cellular differentiation, [SDV]Life Sciences [q-bio], MESH: Flow Cytometry, Plant Science, Cell Separation, Regenerative medicine, Cell therapy, MESH: Hepatocytes, 0302 clinical medicine, Structural Biology, Genes, Reporter, Transduction, Genetic, MESH: Genetic Vectors, Cytochrome P-450 CYP3A, Induced pluripotent stem cell, Promoter Regions, Genetic, MESH: Embryonic Stem Cells, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH: Organ Specificity, Purification, MESH: Lentivirus, MESH: Cytochrome P-450 CYP3A, 0303 health sciences, MESH: Apolipoprotein A-II, Agricultural and Biological Sciences(all), Cell Differentiation, Flow Cytometry, MESH: Transduction, Genetic, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], Liver, Organ Specificity, 030220 oncology & carcinogenesis, General Agricultural and Biological Sciences, Apolipoprotein A-II, MESH: Virus Integration, Biotechnology, Research Article, KOSR, MESH: Cell Differentiation, Virus Integration, Genetic Vectors, Green Fluorescent Proteins, Non-integrating lentiviral vectors, Biology, MESH: Cell Separation, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, MESH: Green Fluorescent Proteins, [SDV.BDD] Life Sciences [q-bio]/Development Biology, MESH: Promoter Regions, Genetic, Humans, Progenitor cell, Tissue-specific progenitor cells, Ecology, Evolution, Behavior and Systematics, Embryonic Stem Cells, 030304 developmental biology, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), Lentivirus, MESH: Genes, Reporter, MESH: Biological Markers, Cell Biology, Embryonic stem cell, Molecular biology, MESH: Cell Line, MESH: DNA, Viral, Transplantation, DNA, Viral, Hepatocytes, Biomarkers, Developmental Biology, MESH: Liver
Abstract

BackgroundHuman pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods.ResultsWe used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration.ConclusionsWe have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also forin vitroapplications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.

Published
2013

16. Draft genome sequences of five strains of [i]Lactobacillus acidophilus[/i] , strain CIP 76.13 T , isolated from humans, strains CIRM-BIA 442 and CIRM-BIA 445, isolated from dairy products, and strains DSM 20242 and DSM 9126 of unknown origin

Author

Pukall Rüdiger, Hélène Falentin, Valentin Loux, Chantal Bizet, Victoria Chuat, Sophie Creno, Dominique Clermont, Laurence Ma, Christiane Bouchier, Sylvie Cousin, Science et Technologie du Lait et de l'Oeuf (STLO), 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), Centre de Ressources biologiques de l'Institut Pasteur - Biological Resource Center of the Institut Pasteur (CRBIP), Institut Pasteur [Paris], Génomique (Plate-Forme) - Genomics Platform, Unité Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH / Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (DSMZ), This communication is an initiative of the European Consortium of Microbial Resource Centers (EMbaRC), supported by the European Commission’s Seventh Framework Programme (FP7, 2007–2013), Research Infrastructures action under the grant agreement no. FP7-228310, European Project: 228310,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2008-1,EMBARC(2009), Centre de Ressources biologiques de l'Institut Pasteur (CRBIP), Génomique (Plate-Forme), Institut Pasteur [Paris] (IP), and Unité Mathématique Informatique et Génome (MIG)

Subjects
Biology, Genome, produit laitier, Microbiology, 03 medical and health sciences, Lactobacillus acidophilus, séquence, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Genetics, souche, Prokaryotes, Molecular Biology, Gene, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, 030306 microbiology, Strain (biology), génome, food and beverages, lactobacillus acidophilus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, annotation, NGS, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Lactobacillus acidophilus is a natural inhabitant of mammalian gastrointestinal systems and is used in dairy and pharmaceutical products. Five draft genome sequences, covering 1,995,790 nucleotides (nt) on average, are divided into 19 to 34 scaffolds covering 1,995 to 2,053 genes. The draft genome sequences were compared to the sequence of the L. acidophilus NCFM dairy strain.

Published
2013

17. Draft genome sequence of Lactobacillus hominis strain CRBIP 24.179τ, isolated from human intestine

Author

Valentin Loux, Sophie Creno, Sylvie Cousin, Chantal Bizet, Dominique Clermont, Christiane Bouchier, Laurence Ma, Centre de Ressources biologiques de l'Institut Pasteur - Biological Resource Center of the Institut Pasteur (CRBIP), Institut Pasteur [Paris], Génomique (Plate-Forme) - Genomics Platform, Unité Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), European Commission's Seventh Framework Programme (FP7, 2007-2013), Research Infrastructures action under the grant agreement no. FP7-228310, Institut Pasteur [Paris] (IP), Unité Mathématique Informatique et Génome (MIG), Centre de Ressources biologiques de l'Institut Pasteur (CRBIP), and Génomique (Plate-Forme)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Human intestine, [SCCO.COMP]Cognitive science/Computer science, Microbiology, 03 medical and health sciences, flore intestinale, intestin, Lactobacillus, Genetics, Prokaryotes, Molecular Biology, 030304 developmental biology, Whole genome sequencing, 0303 health sciences, biology, Contig, Strain (chemistry), 030306 microbiology, food and beverages, biology.organism_classification, C content, Computer science, 3. Good health, séquence du génome, lactobacillus, Informatique (Sciences cognitives), humain, Autre (Sciences du Vivant)
Abstract

We report the draft genome sequence of the strain Lactobacillus hominis CRBIP 24.179 T , isolated from a human clinical sample. The total length of the 28 contigs is about 1.9 Mb, with a G+C content of 37% and 1,983 coding sequences.

Published
2013

18. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota

Author

Claire Cenac, Pierre Monsan, Aurélie Waget, Pascale Klopp, Philippe Valet, Jacques Amar, Jason S. Iacovoni, Jérôme Mariette, Rémy Burcelin, Mathieu Bergé, Jérôme Lluch, Audrey Baylac, Anne Bouloumié, Sandra Grès, Christophe Klopp, Françoise Ouarné, Christine Roques, Olivier Bouchez, Vassilia Theodorou, Matteo Serino, Elodie Luche, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Adhésion Bacterienne et Formation de Biofilms, PRES Université de Toulouse, ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Plateforme Bio-informatique Toulouse Genopole®, UBIA INRA, Toulouse Genopole, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), CRITT Bio-Industrie, Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Service de Médecine Interne et Hypertension Artérielle [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], his work was supported by grants from Agence Nationale pour la Recherche (ANR) to RB and collaborators (ANR-Florinflam and Transflora), in part, by the European Commission's Seventh Framework programme under grant agreement No 241913 (FLORINASH) to RB and by the Benjamin Delessert Foundation to MS., European Project: 241913,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,FLORINASH(2010), Centre National de la Recherche Scientifique - CNRS (FRANCE), Ecole d'Ingénieurs de Purpan - EIP (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Recherche Agronomique - INRA (FRANCE), Institut National des Sciences Appliquées de Toulouse - INSA (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Institut universitaire de France - IUF (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), ToxAlim (Toulouse, France), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés - LISBP (Toulouse, France), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Burcelin, Remy, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Unité de Biométrie et Intelligence Artificielle (ancêtre de MIAT) (UBIA), Institut National de la Recherche Agronomique (INRA), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service d'hypertension artérielle et thérapeutique [CHU Toulouse] (HTA et thérapeutique), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Simon, Marie Francoise, The role of intestinal microflora in non-alcoholic fatty liver disease (NAFLD) - FLORINASH - - EC:FP7:HEALTH2010-01-01 - 2014-12-31 - 241913 - VALID, Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), and Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
Lipopolysaccharides, Male, mictobiota, White adipose tissue, [SDV.GEN] Life Sciences [q-bio]/Genetics, Gut flora, Fatty Acids, Nonesterified, Intestinal absorption, Cecum, Mice, 0302 clinical medicine, gut, metabolic, background, phenotype, diet, MESH: Diabetes Mellitus, Experimental, MESH: Animals, 2. Zero hunger, 0303 health sciences, Glucose tolerance test, MESH: Muscle, Skeletal, MESH: Cytokines, MESH: Fatty Acids, Nonesterified, medicine.diagnostic_test, biology, digestive, oral, and skin physiology, Gastroenterology, food and beverages, Phenotype, Adaptation, Physiological, Intestines, medicine.anatomical_structure, High-fat diet, Liver, 030220 oncology & carcinogenesis, MESH: Permeability, Cytokines, medicine.symptom, MESH: Intestines, medicine.medical_specialty, MESH: Glucose Tolerance Test, MESH: Intestinal Absorption, Médecine humaine et pathologie, Inflammation, Gut microbiota, Diet, High-Fat, MESH: Phenotype, digestive system, Permeability, Diabetes Mellitus, Experimental, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Diabetes mellitus, Internal medicine, medicine, Animals, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Metabolic diseases, MESH: Cecum, Glucose Tolerance Test, MESH: Metagenome, medicine.disease, biology.organism_classification, MESH: Adaptation, Physiological, MESH: Male, Mice, Inbred C57BL, MESH: Diet, High-Fat, Endocrinology, Intestinal Absorption, Immunology, Metagenome, MESH: Lipopolysaccharides, MESH: Liver
Abstract

Chantier qualité GA; International audience; OBJECTIVE: The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. METHODS: The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). RESULTS: Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. CONCLUSIONS: The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Published
2012

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