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1. 2017 publication guidelines for structural modelling of small-angle scattering data from biomolecules in solution: an update

Author

Wayne A. Hendrickson, Lois Pollack, Javier Pérez, Nigel Kirby, Greg L. Hura, Patrice Vachette, Torsten Schwede, Dominique Durand, Jill Trewhella, Ann H. Kwan, John D. Westbrook, Timothy M. Ryan, Dmitri I. Svergun, Andrej Sali, David A. Jacques, Dina Schneidman-Duhovny, Anthony P. Duff, John A. Tainer, J. Mitchell Guss, Masaaki Sugiyama, Andrew E. Whitten, Frank Gabel, School of Molecular and Microbial Biosciences, The University of Sydney [Sydney], Ctr Natl Rech Sci, Inst Biochim & Biophys Mol & Cellulaire, Unite Mixte Rech 8619, Université Paris-Sud - Paris 11 ( UP11 ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), University of Sydney, School od Medicinal Sciences, SWING beamline, Biophysics Group ( SWING ), Synchrotron SOLEIL, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California [San Francisco] ( UCSF ) -California Institute for Quantitative Biosciences, Biozentrum, University of Basel ( Unibas ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Department of Chemistry and Chemical Biology, Center for Integrative Proteomics Research, Rutgers, Rutgers, The State University of New Jersey [New Brunswick] ( RUTGERS ), The University of Sydney, Université Paris-Sud - Paris 11 (UP11), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), SWING beamline, Biophysics Group (SWING), Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] (UCSF), University of California-University of California, Biozentrum [Basel, Suisse], University of Basel (Unibas), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of California [San Francisco] (UC San Francisco), and University of California (UC)-University of California (UC)

Subjects
0301 basic medicine, Models, Molecular, Computer science, MESH : DNA, MESH: Editorial Policies, Biomolecular structure, 01 natural sciences, Field (computer science), small-angle scattering, MESH : Proteins, Data acquisition, X-Ray Diffraction, Structural Biology, MESH : RNA, MESH : Scattering, Small Angle, MESH: Animals, MESH: Proteins, Databases, Protein, integrative structural biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Scope (project management), MESH: DNA, MESH: X-Ray Diffraction, SAXS, Research Papers, 3. Good health, Sample quality, structural modelling, Small-angle scattering, MESH: Models, Molecular, Editorial Policies, MESH: Databases, Protein, MESH : Models, Molecular, 010402 general chemistry, 03 medical and health sciences, MESH : X-Ray Diffraction, MESH: RNA, Scattering, Small Angle, Animals, Humans, publication guidelines, MESH : Databases, Protein, MESH: Scattering, Small Angle, MESH: Humans, Task force, SANS, MESH : Humans, biomolecular structure, Proteins, DNA, Data science, proteins, 0104 chemical sciences, 030104 developmental biology, MESH : Editorial Policies, Data presentation, hybrid structural modelling, RNA, MESH : Animals, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

Updated guidelines are presented for publishing biomolecular small-angle scattering (SAS) experiments so that readers can independently assess the quality of the data and models presented. The focus is on solution scattering experiments with either X-rays (SAXS) or neutrons (SANS), where the primary goal is the generation and testing of three-dimensional models, particularly in the context of integrative/hybrid structural modelling., In 2012, preliminary guidelines were published addressing sample quality, data acquisition and reduction, presentation of scattering data and validation, and modelling for biomolecular small-angle scattering (SAS) experiments. Bio­molecular SAS has since continued to grow and authors have increasingly adopted the preliminary guidelines. In parallel, integrative/hybrid determination of biomolecular structures is a rapidly growing field that is expanding the scope of structural biology. For SAS to contribute maximally to this field, it is essential to ensure open access to the information required for evaluation of the quality of SAS samples and data, as well as the validity of SAS-based structural models. To this end, the preliminary guidelines for data presentation in a publication are reviewed and updated, and the deposition of data and associated models in a public archive is recommended. These guidelines and recommendations have been prepared in consultation with the members of the International Union of Crystallography (IUCr) Small-Angle Scattering and Journals Commissions, the Worldwide Protein Data Bank (wwPDB) Small-Angle Scattering Validation Task Force and additional experts in the field.

Published
2017
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2. The NIP7 protein is required for accurate pre-rRNA processing in human cells

Author

Cédric Hesling, Patricia P. Coltri, Beatriz A. Castilho, Ruth Rimokh, Luis Gustavo Morello, Nilson Ivo Tonin Zanchin, Centro Nacional de Pesquisa em Energia e materiais, Centra Nacional de Pesquisa, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, Equipe 10, Oncogénèse et progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro nacional de Perquisa em Energia e Materiai, centro nacional de Perquisa, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), universidade federal de sao paulo, Universidade Federal de Sao Paulo, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-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 )

Subjects
Poly U, MESH : Cell Line, Ribosome, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, RNA Precursors, MESH : RNA, MESH : Cell Nucleus Structures, RNA Processing, Post-Transcriptional, MESH : RNA Precursors, MESH : RNA Processing, Post-Transcriptional, 0303 health sciences, NIP7, MESH : RNA, Ribosomal, Nuclear Proteins, Cell biology, MESH: Poly U, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, MESH: HEK293 Cells, Eukaryotic Ribosome, MESH : Poly A-U, MESH: RNA Processing, Post-Transcriptional, MESH: RNA Precursors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cell Line, 03 medical and health sciences, MESH: RNA, Genetics, Humans, Eukaryotic Small Ribosomal Subunit, MESH: Cell Nucleus Structures, MESH: Poly A-U, RRNA processing, 030304 developmental biology, MESH: Humans, Eukaryotic Large Ribosomal Subunit, MESH : Humans, MESH : Nuclear Proteins, Ribosomal RNA, SBDS, Molecular biology, MESH: Gene Knockdown Techniques, Cell Nucleus Structures, MESH : HEK293 Cells, MESH: Cell Line, HEK293 Cells, MESH : Poly U, RNA, Ribosomal, Polyribosomes, MESH : Polyribosomes, MESH: RNA, Ribosomal, Poly A-U, RNA, MESH : Gene Knockdown Techniques, MESH: Nuclear Proteins, MESH: Polyribosomes
Abstract

International audience; Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman-Bodian-Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S-80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells.

Published
2011
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3. The human COP9 signalosome protects ubiquitin-conjugating enzyme 3 (UBC3/Cdc34) from beta-transducin repeat-containing protein (betaTrCP)-mediated degradation

Author

Emmanuel Sechet, Elisabetta Bianchi, Lars Rogge, Maria Elena Fernandez-Sanchez, Florence Margottin-Goguet, Immunorégulation, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Cell Line, MESH : Hela Cells, Oligonucleotides, Ubiquitin-conjugating enzyme, Biochemistry, NEDD8, MESH: Down-Regulation, Substrate Specificity, MESH : Down-Regulation, 0302 clinical medicine, Ubiquitin, MESH: Transducin, MESH: Oligonucleotides, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : RNA, MESH : Ubiquitin, MESH: Lentivirus, chemistry.chemical_classification, 0303 health sciences, biology, MESH : Substrate Specificity, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin-Protein Ligase Complexes, Ubiquitin ligase, MESH : Lentivirus, Protein Synthesis and Degradation, 030220 oncology & carcinogenesis, MESH : Peptide Hydrolases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Transducin, Plasmids, MESH: Ubiquitin, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Peptide Hydrolases, MESH : Transducin, MESH : Multiprotein Complexes, Down-Regulation, MESH : Oligonucleotides, Anaphase-Promoting Complex-Cyclosome, Cell Line, 03 medical and health sciences, Downregulation and upregulation, MESH: Plasmids, MESH: RNA, Humans, COP9 signalosome, Molecular Biology, 030304 developmental biology, MESH: Humans, COP9 Signalosome Complex, MESH : Humans, fungi, Lentivirus, MESH: Ubiquitin-Protein Ligase Complexes, Cell Biology, MESH: Multiprotein Complexes, MESH: Cell Line, MESH: Hela Cells, Enzyme, chemistry, MESH : Plasmids, Multiprotein Complexes, Ubiquitin-Conjugating Enzymes, biology.protein, RNA, MESH: Substrate Specificity, MESH : Ubiquitin-Protein Ligase Complexes, HeLa Cells, Peptide Hydrolases
Abstract

International audience; The COP9 signalosome (CSN) is an essential multisubunit complex that regulates the activity of cullin-RING ubiquitin ligases by removing the ubiquitin-like peptide NEDD8 from cullins. Here, we demonstrate that the CSN can affect other components of the ubiquitination cascade. Down-regulation of human CSN4 or CSN5 induced proteasome-mediated degradation of the ubiquitin-conjugating enzyme UBC3/Cdc34. UBC3 was targeted for ubiquitination by the cullin-RING ubiquitin ligase SCF(betaTrCP). This interaction required the acidic C-terminal extension of UBC3, which is absent in ubiquitin-conjugating enzymes of the UBCH5 family. Conversely, the UBC3 acidic domain was sufficient to impart sensitivity to SCF(betaTrCP)-mediated ubiquitination to UBCH5 enzymes. Our work indicates that the CSN is necessary to ensure the stability of selected ubiquitin-conjugating enzymes and uncovers a novel pathway of regulation of ubiquitination processes.

Published
2010
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4. Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake

Author

Adriana Márquez-Quiñones, Dominique Langin, Karine Clément, Wim H. M. Saris, Teodora Handjieva-Darlenska, Marion Combes, Ping Wang, Andreas Pfeiffer, Dimitris K. Babalis, David M. Mutch, Thomas Meinert Larsen, Susan A. Jebb, Claus Holst, Edwin C. M. Mariman, Hubert Vidal, Arne Astrup, Nathalie Viguerie, Pavla Kalouskova, Balbine Roussel, Cyrille Debard, J. Alfredo Martínez, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Santé Publique et Informatique Médicale (SPIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Human Health and Nutritional Sciences, University of Guelph, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Human Biology, Maastricht University [Maastricht], Institute of Preventive Medicine, Copenhagen University Hospitals, Department of Physiology and Nutrition, Universidad de Navarra [Pamplona] (UNAV), Department of Pharmacology and Toxicology, Medical Faculty, Medical University, Obesity Management Centre, Institute of Endocrinology, Human Nutrition Research, Elsie Widdowson Laboratory, Department of Internal Medicine, University Hospital of Heraklion, Department of Clinical Nutrition, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Human Nutrition, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], European Community [FP6-513946], Institut National de la Sante et de la Recherche Medicale, Region Midi-Pyrenees, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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 National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Santé Publique et Informatique Médicale ( SPIM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Universidad de Navarra [Pamplona] ( UNAV ), Charité Universitäts Medizin Berlin, University of Copenhagen ( KU ), Centre de Recherche en Nutrition Humaine d'Ile-de-France ( CRNH-IDF ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut National Agronomique Paris-Grignon ( INA P-G ) -CETAF-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Paris 13 (UP13)-CETAF-Institut National Agronomique Paris-Grignon (INA P-G)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut de Veille Sanitaire (INVS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humane Biologie, RS: NUTRIM - R4 - Gene-environment interaction, and RS: NUTRIM - R1 - Metabolic Syndrome

Subjects
MESH: Treatment Failure, Blood Pressure, MESH: Energy Intake, Transcriptome, 0302 clinical medicine, HIGH-PROTEIN, Models, MESH: Models, Genetic, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, MESH: Treatment Outcome, 0303 health sciences, MACRONUTRIENT, Reducing, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Blood Pressure, MESH: Follow-Up Studies, LOW-FAT, Gene expression profiling, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, LOSS MAINTENANCE, MESH : Adipose Tissue, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Weight Loss, MESH : Treatment Failure, Genetic, Humans, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, MESH : Gene Expression Profiling, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, Anthropometry, medicine.disease, Obesity, Endocrinology, MICROARRAY DATA, Energy intake, MESH: Female, Calorie, Time Factors, Medicine (miscellaneous), Adipose tissue, MESH : Models, Genetic, HUMAN OBESITY, Weight loss, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : RNA, MESH: Obesity, MESH : Female, Treatment Failure, MESH : Diet, Reducing, 2. Zero hunger, MESH: Diet, Reducing, Nutrition and Dietetics, Reverse Transcriptase Polymerase Chain Reaction, MESH : Adult, ADIPOCYTES, Glycemic index, Treatment Outcome, MESH : Obesity, Female, medicine.symptom, Dieting, MESH : Time Factors, Adult, 030209 endocrinology & metabolism, MESH : Treatment Outcome, Biology, DiOGenes, MESH: RNA, Internal medicine, Weight Loss, medicine, MESH : Blood Pressure, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, LOSS DIETS, Models, Genetic, Gene Expression Profiling, MESH: Time Factors, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, GLYCEMIC INDEX, RNA, MESH : Weight Loss, Energy Intake, Follow-Up Studies
Abstract

Background: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. Objective: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. Design: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. Conclusions: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control. This trial was registered at clinicaltrials.gov as NCT00390637. © 2010 American Society for Nutrition.

Published
2010
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5. A minimal model for hepatic fatty acid balance during fasting: Application to PPAR alpha-deficient mice

Author

J. van Milgen, Anne Siegel, P. Blavy, Hervé Guillou, Florence Gondret, Pascal G.P. Martin, Ovidiu Radulescu, Sandrine Lagarrigue, Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire de Pharmacologie et Toxicologie, UR66, INRA, Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), CNRS, Centre National de la Recherche Scientifique (CNRS), Systèmes d'élevage, nutrition animale et humaine (SENAH), 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), Génétique Animale (GARen), 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)-Ecole Nationale Supérieure Agronomique de Rennes, Génétique fonctionnelle, agronomie et santé [IFR 140] (GFAS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST-Ecole Nationale Supérieure Agronomique de Rennes, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Biological systems and models, bioinformatics and sequences ( SYMBIOSE ), Institut de Recherche en Informatique et Systèmes Aléatoires ( IRISA ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique ( Inria ), Institut National de la Recherche Agronomique ( INRA ), Université de Rennes ( UNIV-RENNES ), Institut de Recherche Mathématique de Rennes ( IRMAR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST-École normale supérieure - Rennes ( ENS Rennes ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National des Sciences Appliquées ( INSA ) -Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, MESH: Oxidation-Reduction, obesity, Peroxisome proliferator-activated receptor, Adipose tissue, MESH : Genotype, chain, MESH : Fasting, Polymerase Chain Reaction, adipose-tissue, MESH : Knockout, MESH: Genotype, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH : Inbred C57BL, Gene expression, MESH: Models, MESH : RNA, MESH: Animals, MESH: PPAR alpha, MESH : Fatty Acids, MESH : Polymerase Chain Reaction, MESH: Knockout, chemistry.chemical_classification, Mice, Knockout, 0303 health sciences, MESH : Gene Expression Regulation, Applied Mathematics, Fatty Acids, MESH: Messenger, null mice, General Medicine, Fasting, MESH: Gene Expression Regulation, MESH: Fatty Acids, Real-time polymerase chain reaction, Liver, rat-liver peroxisomes, Modeling and Simulation, Knockout mouse, MESH : Models, General Agricultural and Biological Sciences, Systems biology, Oxidation-Reduction, Statistics and Probability, medicine.medical_specialty, MESH: Biological, Genotype, MESH : Messenger, oxidation, MESH : Male, MESH : PPAR alpha, MESH: Fasting, Biology, Linoleoyl-CoA Desaturase, Models, Biological, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, MESH: RNA, Internal medicine, MESH : Mice, medicine, Animals, PPAR alpha, mammals, RNA, Messenger, MESH: Mice, mouse, 030304 developmental biology, MESH : Oxidation-Reduction, MESH: Linoleoyl-CoA Desaturase, General Immunology and Microbiology, Fatty acid metabolism, Modeling, Fatty acid, MESH : Liver, [ SDV.GEN.GA ] Life Sciences [q-bio]/Genetics/Animal genetics, MESH: Polymerase Chain Reaction, Metabolism, MESH : Biological, MESH: Inbred C57BL, gene-expression, MESH : Linoleoyl-CoA Desaturase, MESH: Male, Mice, Inbred C57BL, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Endocrinology, chemistry, Gene Expression Regulation, MESH : Animals, metabolism, 030217 neurology & neurosurgery, Knockout mice, MESH: Liver
Abstract

The purpose of this study is to identify the hierarchy of importance amongst pathways involved in fatty acid (FA) metabolism and their regulators in the control of hepatic FA composition. A modeling approach was applied to experimental data obtained during fasting in PPAR α knockout (KO) mice and wild-type mice. A step-by-step procedure was used in which a very simple model was completed by additional pathways until the model fitted correctly the measured quantities of FA in the liver. The resulting model included FA uptake by the liver, FA oxidation, elongation and desaturation of FA, which were found active in both genotypes during fasting. From the model analysis we concluded that PPAR α had a strong effect on FA oxidation. There were no indications that this effect changes during the fasting period, and it was thus considered to be constant. In PPAR α KO mice, FA uptake was identified as the main pathway responsible for FA variation in the liver. The models showed that FA were oxidized at a constant and small rate, whereas desaturation of FA also occurred during fasting. The latter observation was rather unexpected, but was confirmed experimentally by the measurement of delta-6-desaturase mRNA using real-time quantitative PCR (QPCR). These results confirm that mathematical models can be a useful tool in identifying new biological hypotheses and nutritional routes in metabolism.

Published
2009
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6. Contribution of energy restriction and macronutrient composition to changes in adipose tissue gene expression during dietary weight-loss programs in obese women

Author

Claus Holst, Nathalie Vega, Moira A. Taylor, J. Alfredo Martínez, Eva Klimcakova, Thorkild I. A. Sørensen, Dominique Langin, Sébastien Déjean, Jean M. Oppert, Peter Arner, Hubert Vidal, Nathalie Viguerie, Karine Clément, Frédéric Capel, Wim H. M. Saris, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche sur les obésités, CHU Toulouse [Toulouse]-Laboratoire, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Lyon-Sud, FACULTE DE LYON, Centre de Recherche en Nutrition Humaine, Hospices Civils de Lyon (HCL), Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Midicine Karolinska Institute, Karolinska University Hospital Huddinge, Department of Sports Medicine of Charles University, Faculty of Medicine Charles University, Department of Physiology and nutrition University of Navarra, Universidad de Navarra [Pamplona] (UNAV), Department of Human Biology Nutrition and Toxicology Research Institute, Maastricht University [Maastricht], The Netherlands Institute of Preventive Medicine, Institute of Preventive Medicine, School of Biomedical Sciences Queen's Medical Center, University of Nottingham Medical School, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Department of Nutrition and Endocrinology AP / HP, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR 31 Louis Bugnard ( IFR 31 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), Régulations métaboliques, nutrition et diabètes - UM55 ( RMND UM55 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Universidad de Navarra [Pamplona] ( UNAV ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Humane Biologie, RS: NUTRIM - R1 - Metabolic Syndrome, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], 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)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Transcription, Genetic, Endocrinology, Diabetes and Metabolism, MESH: Energy Intake, Biochemistry, Body Mass Index, 0302 clinical medicine, Endocrinology, Gene expression, MESH: Genetic Variation, MESH : Adaptor Proteins, Signal Transducing, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Addipose tissue, Reducing, MESH: Mitochondrial Proteins, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, Adipose Tissue, Body Composition, MESH: Adipose Tissue, medicine.medical_specialty, Diet, Reducing, MESH : Body Composition, MESH : Adipose Tissue, MESH: Body Mass Index, MESH : Receptors, Glucocorticoid, 03 medical and health sciences, MESH: Weight Loss, Genetic, Humans, MESH : Fatty Acid-Binding Proteins, MESH : Mitochondrial Proteins, MESH: Adaptor Proteins, Signal Transducing, MESH: Humans, MESH : Humans, Signal Transducing, Genetic Variation, MESH: Adult, Autophagy-Related Protein 8 Family, MESH: Body Composition, medicine.disease, Obesity, MESH : Energy Metabolism, MESH : Body Mass Index, Energy intake, Body mass index, MESH: Female, Candidate gene, MESH: Receptors, Glucocorticoid, Clinical Biochemistry, Adipose tissue, Blood lipids, Glucocorticoid, Weight loss, Sirtuin 3, Receptors, MESH : RNA, Sirtuins, MESH: Obesity, MESH : Female, Nutrición y dietética [Ciencias de la Salud], MESH : Diet, Reducing, 2. Zero hunger, MESH : Sirtuins, MESH: Diet, Reducing, Microfilament Proteins, MESH: Energy Metabolism, Adaptor Proteins, MESH : Adult, MESH: Sirtuins, MESH : Obesity, Female, medicine.symptom, Transcription, Adult, MESH : Microfilament Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, Fatty Acid-Binding Proteins, MESH: Fatty Acid-Binding Proteins, Mitochondrial Proteins, MESH: Microfilament Proteins, Receptors, Glucocorticoid, MESH : Genetic Variation, MESH: RNA, Internal medicine, Weight Loss, medicine, 030304 developmental biology, Adaptor Proteins, Signal Transducing, MESH: Transcription, Genetic, Biochemistry (medical), MESH : Transcription, Genetic, MESH : Energy Intake, Diet, MESH: Oligonucleotide Array Sequence Analysis, RNA, MESH : Weight Loss, Energy Intake, Energy Metabolism
Abstract

Context: Hypoenergetic diets are used to reduce body fat mass and metabolic risk factors in obese subjects. The molecular changes in adipose tissue associated with weight loss and specifically related to the dietary composition are poorly understood. Objective: We investigated adipose tissue gene expression from human obese women according to energy deficit and, the fat and carbohydrate content of the diet. Design & setting: Obese subjects recruited among 8 European clinical centers followed 10 weeks of either a low fat (high carbohydrate) or a moderate fat (low carbohydrate) hypoenergetic diet. Subjects: Two sets of 47 women in each dietary arm were selected among 648 subjects matched for anthropometric and biological parameters. Main Outcome Measure: We measured adipose tissue gene expression changes in one set using a candidate gene approach. The other set was used to survey 24469 transcripts using DNA microarrays. Results were analyzed using dedicated statistical methods. Diet-sensitive regulations were confirmed on the other set of subjects. Results: The two diets induced similar weight loss and similar changes for most of the biological variables except for components of the blood lipid profile. A thousand genes were regulated by energy restriction. We validated an effect of the fat-to-carbohydrate ratio for five genes (FABP4, NR3C1, SIRT3, FNTA and GABARAPL2) with increased expression during the moderate fat diet. Conclusions: Energy restriction had a more pronounced impact on variations in human adipose tissue gene expression than macronutrient composition. The macronutrient-sensitive regulation of a subset of genes may influence adipose tissue function and metabolic response. AD - INSERM, U858, Laboratoire de Recherches sur les Obesites, Institut de Medecine Moleculaire de Rangueil, Toulouse; Universite Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse; Centre Hospitalier Universitaire de Toulouse, France; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; INSERM, UMR -870; INRA U-1235; Faculte de Medecine Lyon-Sud universite de Lyon 1; Centre de Recherche en Nutrition Humaine, Hospices civils de Lyon; Lyon, France; Institut de Mathematiques de Toulouse UMR 5219, Universite Paul-Sabatier, Toulouse, France; Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Sports Medicine, Centre of Preventive Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic; Franco-Czech Laboratory for Clinical Research on Obesity, Prague, Czech Republic; Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain; Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands; Institute of Preventive Medicine, Centre for Health and Society, Copenhagen University Hospital, Copenhagen, Denmark; School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham Medical School, Nottingham, United Kingdom; INSERM, Nutriomique U872 (Team 7), 75004 Paris, France; Universites Pierre et Marie Curie-Paris6, UMR-S 872, Cordelier Research Center & Paris Descartes, 75006 Paris; and Assistance Publique/Hopitaux de Paris (AP-HP), Pitie Salpetriere Hospital, Nutrition and Endocrinology department, 75013 Paris, France.

Published
2008
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7. Bsr, a nuclear-retained RNA with monoallelic expression

Author

Jérôme Cavaillé, Maud Marques, Eugenia Basyuk, Edouard Bertrand, Virginie Marty, Hélène Royo, Laboratoire de biologie moléculaire eucaryote du CNRS ( LBME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Biologie du Développement de Marseille ( IBDM ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherches sur la Cognition Animale [Toulouse] ( CRCA ), Institut de minéralogie et de physique des milieux condensés ( IMPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IPG PARIS-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Departament Geodinàmica i Geofísica, Facultat de Geologia, Laboratoire de Physique Statistique de l'ENS ( LPS ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Colloïdes et Matériaux Divisés ( LCMD ), ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ), Liquides Ioniques et Interfaces Chargées ( LI2C ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -ESPCI ParisTech-Centre National de la Recherche Scientifique ( CNRS ), Ecole Nationale de la Santé Publique ( ENSP ), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Centre de recherches Paul Pascal ( CRPP ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-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), Département de biologie [Sherbrooke] (UdeS), Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Laboratoire de Physique Statistique de l'ENS (LPS), Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Colloïdes et Matériaux Divisés (LCMD), Centre National de la Recherche Scientifique (CNRS)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Liquides Ioniques et Interfaces Chargées (LI2C), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Ecole Nationale de la Santé Publique (ENSP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de recherches Paul Pascal (CRPP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris)

Subjects
MESH: Hydroxamic Acids, RNA, Untranslated, MESH : RNA, Messenger, MESH: Introns, RNA Stability, Hydroxamic Acids, RNA Transport, MESH: RNA, Untranslated, 0302 clinical medicine, MESH: RNA Transport, Transcription (biology), Gene cluster, MESH : RNA, MESH: Animals, MESH : Cell Nucleus Structures, MESH : Female, MESH : RNA Transport, Genetics, 0303 health sciences, MESH : Cell Nucleus, MESH : Rats, MESH: RNA Stability, Articles, MESH : RNA Stability, Non-coding RNA, medicine.anatomical_structure, RNA splicing, Female, MESH : RNA Splicing, MESH: Cell Nucleus, MESH : RNA, Untranslated, MESH: Rats, RNA Splicing, MESH: Cytoplasmic Granules, Biology, Cytoplasmic Granules, MESH : Rats, Wistar, MESH : Introns, 03 medical and health sciences, MESH: RNA, MESH : Fibroblasts, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Cell Nucleus Structures, RNA, Messenger, Rats, Wistar, Molecular Biology, Gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Alleles, MESH: RNA, Messenger, 030304 developmental biology, Cell Nucleus, MESH : Hydroxamic Acids, MESH: Alleles, MESH : Cytoplasmic Granules, Intron, RNA, MESH: Rats, Wistar, Cell Biology, Fibroblasts, Cell Nucleus Structures, Introns, Rats, Cell nucleus, MESH: Fibroblasts, MESH : Animals, MESH: RNA Splicing, MESH : Alleles, MESH: Female, 030217 neurology & neurosurgery
Abstract

The imprinted Dlk1-Gtl2 and Prader-Willi syndrome (PWS) regions are characterized by a complex noncoding transcription unit spanning arrays of tandemly repeated C/D RNA genes. These noncoding RNAs (ncRNAs) are thought to play an essential but still poorly understood role. To better understand the intracellular fate of these large ncRNAs, fluorescence in situ hybridization was carried out at the rat Dlk1-Gtl2 domain. This locus contains a ∼100-kb-long gene cluster comprising 86 homologous RBII-36 C/D RNA gene copies, all of them intron-encoded within the ncRNA gene Bsr. Here, we demonstrate that the Bsr gene is monoallelically expressed in primary rat embryonic fibroblasts as well as in hypothalamic neurons and yields a large amount of unspliced and spliced RNAs at the transcription site, mostly as elongated RNA signals. Surprisingly, spliced Bsr RNAs released from the transcription site mainly concentrate as numerous, stable nuclear foci that do not colocalize with any known subnuclear structures. On drug treatments, a fraction of Bsr RNA relocalizes to the cytoplasm and associates with stress granules (SGs), but not with P-bodies, pointing to a potential link between SGs and the metabolism of ncRNA. Thus, Bsr might represent a novel type of nuclear-retained transcript.

Published
2007
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8. Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors

Author

Mandard, Stéphane, Stienstra, Rinke, Escher, Pascal, Tan, Nguan Soon, Kim, Insook, Gonzalez, Frank, Wahli, Walter, Desvergne, Béatrice, Müller, Michael, Kersten, Sander, Nutrition, Metabolism and Genomics group and Nutrigenomics Consortium ( NMG ), Wageningen University and Research Centre [Wageningen] ( WUR ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institute of Physiology, University of Basel ( Unibas ), Center for Integrative Genomics - Institute of Bioinformatics, Génopode ( CIG ), University of Lausanne, Laboratory of Metabolism, National Cancer Institute ( NIH ), This study was supported by the Netherlands Organization for Scientific Research (NWO), with additional support from the Dutch Diabetes Foundation, the Royal Netherlands Academy of Art and Sciences (KNAW), Wageningen Center for Food Sciences, the Center for Human Nutrigenomics, the Swiss National Science Foundation and the Human Frontier Science Program., Nutrition, Metabolism and Genomics group and Nutrigenomics Consortium (NMG), Wageningen University and Research [Wageningen] (WUR), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), University of Basel (Unibas), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), National Cancer Institute [Bethesda] (NCI-NIH), and National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)

Subjects
MESH: DNA Primers, MESH: Rats, glycogen synthase 2, MESH: Peroxisome Proliferator-Activated Receptors, MESH : Hepatocytes, PPRE, liver, MESH: Mice, Knockout, PPAR, MESH: Chromatin, MESH : Gene Expression Regulation, Enzymologic, MESH: Hepatocytes, MESH: RNA, MESH : Mice, MESH : RNA, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, HNF4α, MESH : Polymerase Chain Reaction, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Glycogen Synthase, MESH : Chromatin, MESH : Rats, MESH: Transcription, Genetic, MESH: Gene Expression Regulation, Enzymologic, MESH : Transcription, Genetic, MESH: Polymerase Chain Reaction, MESH : Peroxisome Proliferator-Activated Receptors, adipose tissue, gene transcription, MESH : Mice, Knockout, MESH : DNA Primers, MESH : Animals, microarray, MESH : Glycogen Synthase
Abstract

International audience; Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen in liver and adipose tissue, yet little is known about regulation of Gys-2 transcription. The peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of lipid and glucose metabolism and might be hypothesized to govern glycogen synthesis as well. Here, we show that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma. Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-, PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta, and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in mouse 3T3-L1 adipocytes. In liver, PPARalpha deletion leads to decreased glycogen levels in the refed state, which is paralleled by decreased expression of Gys-2 in fasted and refed state. Two putative PPAR response elements (PPREs) were identified in the mouse Gys-2 gene: one in the upstream promoter (DR-1prom) and one in intron 1 (DR-1int). It is shown that DR-1int is the response element for PPARs, while DR-1prom is the response element for Hepatic Nuclear Factor 4 alpha (HNF4alpha). In adipose tissue, which does not express HNF4alpha, DR-1prom is occupied by PPARbeta/delta and PPARgamma, yet binding does not translate into transcriptional activation of Gys-2. Overall, we conclude that mouse Gys-2 is a novel PPAR target gene and that transactivation by PPARs and HNF4alpha is mediated by two distinct response elements.

Published
2007
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9. The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity

Author

Marc Piechaczyk, Jean-Michel Mesnard, Charlotte Arpin, Gilles Gaudray, Christian Devaux, Jihane Basbous, Infections rétrovirales et signalisation cellulaire ( IRSC ), Université Montpellier 1 ( UM1 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), ARC, Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
Transcription, Genetic, MESH : Hela Cells, Proto-Oncogene Proteins c-jun, Retroviridae Proteins, MESH: Streptavidin, MESH : Blotting, Western, Biochemistry, MESH: Down-Regulation, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Transcription (biology), Genes, Reporter, MESH: Gene Products, tax, MESH : Trans-Activation (Genetics), MESH: Animals, MESH : Viral Proteins, 0303 health sciences, c-jun, MESH : Protein Binding, MESH: Transcription Factors, MESH : beta-Galactosidase, MESH : Precipitin Tests, MESH : Human T-lymphotropic virus 1, MESH: Transcription Factor AP-1, MESH: Leucine Zippers, 3. Good health, MESH: COS Cells, MESH: Promoter Regions (Genetics), Basic-Leucine Zipper Transcription Factors, MESH : Transcription Factor AP-1, 030220 oncology & carcinogenesis, COS Cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, JunB, MESH : Protein Structure, Tertiary, MESH : Proto-Oncogene Proteins c-jun, Transcriptional Activation, MESH : Glutathione Transferase, Blotting, Western, Biotin, Down-Regulation, MESH: Basic-Leucine Zipper Transcription Factors, Transfection, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 03 medical and health sciences, Viral Proteins, MESH : Basic-Leucine Zipper Transcription Factors, Humans, MESH: Protein Binding, MESH: Blotting, Western, Collagenases, E2F, Molecular Biology, MESH: Glutathione Transferase, MESH: Human T-lymphotropic virus 1, MESH: Humans, MESH: Proto-Oncogene Proteins c-jun, MESH: Genes, Reporter, MESH : Humans, Precipitin Tests, MESH : Promoter Regions (Genetics), Protein Structure, Tertiary, MESH : Streptavidin, Microscopy, Fluorescence, MESH: Binding Sites, HTLV-1, MESH: Luciferases, HeLa Cells, Transcription Factors, Time Factors, MESH : Transcription Factors, MESH : Microscopy, Fluorescence, MESH : DNA, Complementary, MESH: Collagenases, MESH: Microscopy, Fluorescence, MESH : Biotin, MESH : Down-Regulation, Transactivation, hemic and lymphatic diseases, MESH : RNA, MESH: Precipitin Tests, Luciferases, Promoter Regions, Genetic, Glutathione Transferase, Human T-lymphotropic virus 1, MESH : Collagenases, Gene Products, tax, MESH : Genes, Reporter, MESH: beta-Galactosidase, MESH : Dimerization, MESH: Genome, Viral, MESH : Transfection, MESH : COS Cells, Dimerization, MESH : Genome, Viral, Protein Binding, MESH : Time Factors, Leucine zipper, DNA, Complementary, JUNB, [SDV.CAN]Life Sciences [q-bio]/Cancer, Genome, Viral, Biology, MESH: Two-Hybrid System Techniques, MESH: RNA, Two-Hybrid System Techniques, MESH: Biotin, Animals, Transcription factor, 030304 developmental biology, MESH : Luciferases, Leucine Zippers, Binding Sites, Activator (genetics), MESH : Gene Products, tax, MESH: Transcription, Genetic, MESH: Transfection, MESH: Time Factors, c-Jun, MESH : Transcription, Genetic, Cell Biology, MESH: DNA, Complementary, beta-Galactosidase, AP-1, Molecular biology, MESH: Viral Proteins, Transcription Factor AP-1, MESH: Hela Cells, MESH: Dimerization, MESH : Two-Hybrid System Techniques, MESH: Trans-Activation (Genetics), RNA, MESH : Leucine Zippers, Streptavidin, MESH : Animals, MESH : Binding Sites
Abstract

The human T-cell leukemia virus type I (HTLV-I)-encoded Tax protein activates transcription from the viral promoter via association with the cellular basic leucine zipper factor cAMP-response element-binding protein-2. Tax is also able to induce cellular transformation of T lymphocytes probably by modulating transcriptional activity of cellular factors, including nuclear factor-kappaB, E2F, activator protein-1 (AP-1), and p53. Recently, we characterized in HTLV-I-infected cells the presence of a novel viral protein, HBZ, encoded by the complementary strand of the HTLV-I RNA genome (Gaudray, G., Gachon, F., Basbous, J., Biard-Piechaczyk, M., Devaux, C., and Mesnard, J.-M. (2002) J. Virol. 76, 12813-12822). HBZ is a nuclear basic leucine zipper protein that down-regulates Tax-dependent viral transcription by inhibiting the binding of cAMP-response element-binding protein-2 to the HTLV-I promoter. In searching for other cellular targets of HBZ, we identified two members of the Jun family, JunB and c-Jun. Co-immunoprecipitation and cellular colocalization confirmed that HBZ interacts in vivo with JunB and c-Jun. When transiently introduced into CEM cells with a reporter gene containing the AP-1 site from the collagenase promoter, HBZ suppressed transactivation by c-Jun. On the other hand, the combination of HBZ with Jun-B had higher transcriptional activity than JunB alone. Consistent with the structure of its basic domain, we demonstrate that HBZ decreases the DNA-binding activity of c-Jun and JunB. Last, we show that c-Jun is no longer capable of activating the basal expression of the HTLV-I promoter in the presence of HBZ in vivo. Our results support the hypothesis that HBZ could be a negative modulator of the Tax effect by controlling Tax expression at the transcriptional level and by attenuating activation of AP-1 by Tax.

Published
2003
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10. The tRNA-like domains of E coli and A.aeolicus transfer-messenger RNA: structural and functional studies

Author

Valérie Bordeau, Frédéric Dardel, Sophie Corvaisier, Sylvie Nonin-Lecomte, Brice Felden, Cyril Gaudin, Carine Tisné, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Etude du 'Rnome' bacterien. Identification et Caracterisation d'Acides Ribonucleiques Impliques Dans la Survie et la Virulence', Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH : Escherichia coli, MESH: Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, MESH : RNA, Messenger, MESH : Molecular Sequence Data, Protein Conformation, MESH: Protein Structure, Secondary, MESH: Base Sequence, Crystallography, X-Ray, Ribosome, Protein Structure, Secondary, MESH: Recombinant Proteins, chemistry.chemical_compound, MESH: Protein Structure, Tertiary, Protein structure, MESH: Protein Conformation, MESH: Structure-Activity Relationship, RNA, Transfer, Structural Biology, MESH : Structure-Activity Relationship, MESH : RNA, RNA Processing, Post-Transcriptional, MESH : Protein Conformation, MESH : RNA Processing, Post-Transcriptional, 0303 health sciences, Alanine, biology, MESH : Peptides, MESH: Escherichia coli, MESH: Peptides, 030302 biochemistry & molecular biology, MESH : Protein Binding, Hydrogen-Ion Concentration, Recombinant Proteins, Biochemistry, Transfer RNA, MESH : Protein Structure, Tertiary, Protein Binding, MESH: RNA Processing, Post-Transcriptional, MESH : Recombinant Proteins, MESH: Alanine, Molecular Sequence Data, MESH : RNA, Transfer, Pseudouridine, 03 medical and health sciences, Structure-Activity Relationship, MESH : Hydrogen-Ion Concentration, MESH: RNA, Escherichia coli, MESH: Protein Binding, MESH : Bacteria, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: RNA, Messenger, Aquifex aeolicus, MESH: Molecular Sequence Data, Bacteria, Base Sequence, MESH: Magnetic Resonance Spectroscopy, RNA, biology.organism_classification, MESH: RNA, Transfer, MESH: Crystallography, X-Ray, Protein Structure, Tertiary, MESH: Bacteria, chemistry, MESH : Magnetic Resonance Spectroscopy, MESH : Base Sequence, MESH : Protein Structure, Secondary, MESH : Alanine, MESH : Crystallography, X-Ray, Peptides, Trans-translation, Transfer-messenger RNA
Abstract

International audience; Transfer-messenger RNA (tmRNA, 10Sa RNA or ssrA) acts to rescue stalled bacterial ribosomes while encoding a peptide tag added trans-translationally to the nascent peptide, targeting it for proteolysis. The understanding at molecular level of this ubiquitous quality control system in eubacteria requires structural information. Here, we describe the purification and structural analysis of a functional fragment of both Aquifex aeolicus and Escherichia coli tmRNA, recapitulating their tRNA-like domain, which were expressed in vivo from synthetic genes. Both recombinant RNA are correctly processed at both 5' and 3' ends and are produced in quantities suitable for structural analysis by NMR and/or X-ray crystallography. The sequence and solution structure of the tRNA-like domains were analysed by various methods including structural mapping with chemical and enzymatic probes and 2D NMR spectroscopy. The minimalist RNAs contain two post-transcriptional base modifications, 5-methyluridine and pseudouridine, as the full-length tmRNA. Both RNAs fold into three stems, a D-analogue, a T-loop and a GAAA tetra-loop. 2D NMR analysis of the imino proton resonances of both RNAs allowed the assignment of the three stems and of a number of tertiary interactions. It shows the existence of interactions between the TPsiC-loop and the D-analogue, exhibiting a number of similarities and also differences with the canonical tRNA fold, indicating that RNA tertiary interactions can be modulated according to the sequence and secondary structure contexts. Furthermore, the E.coli minimalist RNA is aminoacylatable with alanine with a catalytic efficiency an order of magnitude higher than that for full-length tmRNA.

Published
2003
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11. RNAi-directed assembly of heterochromatin in fission yeast

Author

André Verdel, Danesh Moazed, Verdel, Andre, Department of cell biology, and Harvard Medical School [Boston] ( HMS )

Subjects
Euchromatin, MESH : Models, Genetic, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Models, Biological, MESH : RNA, Small Interfering, Biochemistry, Histone methylation, Histones, Structural Biology, Heterochromatin, MESH : RNA, RNA, Small Interfering, Heterochromatin assembly, Genetics, Genome, MESH : Chromatin, MESH : Histone Deacetylases, EZH2, Clr4, Chromatin, Transcriptional gene silencing, MESH : Lysine, MESH : RNA Replicase, RNA Interference, Epigenetics, RNA Polymerase II, MESH : RNA Polymerase II, RNA-induced transcriptional silencing, Biophysics, RITS, Biology, Methylation, Models, Biological, Histone Deacetylases, Schizosaccharomyces, Animals, MESH : Histones, Molecular Biology, RNA, Double-Stranded, Histone binding, Models, Genetic, MESH : Heterochromatin, Lysine, fungi, MESH : RNA, Double-Stranded, Cell Biology, MESH : Methylation, RNA-Dependent RNA Polymerase, MESH : Schizosaccharomyces, RNAi, RNA, Heterochromatin protein 1, MESH : Animals, MESH : RNA Interference, MESH : Genome, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract

International audience; Heterochromatin is an epigenetically heritable and conserved feature of eukaryotic chromosomes with important roles in chromosome segregation, genome stability, and gene regulation. The formation of heterochromatin involves an ordered array of chromatin changes, including histone deacetylation, histone H3-lysine 9 methylation, and recruitment of histone binding proteins such as Swi6/HP1. Recent discoveries have uncovered a role for the RNA interference (RNAi) pathway in heterochromatin assembly in the fission yeast Schizosaccharomyces pombe and other eukaryotes. Purification of two RNAi complexes, RITS and RDRC, from fission yeast has provided further insight into the mechanism of RNAi-mediated heterochromatin assembly. These discoveries have given rise to a model in which small interfering RNA molecules act as specificity factors that initiate epigenetic chromatin modifications and double strand RNA synthesis at specific chromosome regions.

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12. Gene expression profiling of human skeletal muscle in response to stabilized weight loss

Author

Carine Valle, Nathalie Viguerie, Claire Thalamas, Anne Le Bouil, Dominique Langin, P. Barbe, Jean-Philippe Bastard, Sébastien Déjean, Karine Clément, Dominique Larrouy, Bertrand Diquet, Véronique Pelloux, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC - Biotherapie - Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie de l'Adipocyte et des Cellules Hepatiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de la Médecine, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Mathématiques de Toulouse UMR5219 ( IMT ), Université Toulouse 1 Capitole ( UT1 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-PRES Université de Toulouse-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], and Université Paris Diderot - Paris 7 ( UPD7 )

Subjects
MESH : Basal Metabolism, Medicine (miscellaneous), MESH: Carbon Dioxide, Polymerase Chain Reaction, Absorptiometry, Photon, 0302 clinical medicine, Weight loss, MESH : RNA, MESH: Obesity, MESH : Female, MESH: Oxygen Consumption, MESH : Muscle, Skeletal, MESH : Oxygen Consumption, MESH : Polymerase Chain Reaction, MESH : Diet, Reducing, Oligonucleotide Array Sequence Analysis, 2. Zero hunger, MESH: Diet, Reducing, 0303 health sciences, MESH: Muscle, Skeletal, Nutrition and Dietetics, MESH: Middle Aged, Middle Aged, MESH : Adult, MESH: Basal Metabolism, MESH : Oligonucleotide Array Sequence Analysis, MESH : Carbon Dioxide, medicine.anatomical_structure, Body Composition, Female, MESH : Obesity, medicine.symptom, MESH: Calorimetry, Indirect, Adult, medicine.medical_specialty, Diet, Reducing, MESH : Body Composition, Calorie restriction, PDK4, 030209 endocrinology & metabolism, MESH: Absorptiometry, Photon, Carbohydrate metabolism, Biology, 03 medical and health sciences, MESH: Weight Loss, MESH: Gene Expression Profiling, Oxygen Consumption, MESH: RNA, Internal medicine, Weight Loss, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, MESH : Middle Aged, Resting energy expenditure, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, Muscle, Skeletal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Absorptiometry, Photon, 030304 developmental biology, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, Skeletal muscle, Calorimetry, Indirect, MESH: Adult, MESH: Polymerase Chain Reaction, MESH: Body Composition, Carbon Dioxide, Gene expression profiling, Endocrinology, Basal metabolic rate, MESH: Oligonucleotide Array Sequence Analysis, RNA, Basal Metabolism, MESH : Weight Loss, MESH : Calorimetry, Indirect, MESH: Female
Abstract

International audience; BACKGROUND: Diet-induced weight reduction promotes a decrease in resting energy expenditure that could partly explain the difficulty in maintaining reduced body mass. Whether this reduction remains after stabilized weight loss is still controversial, and the molecular mechanisms are unknown. OBJECTIVE: The objective was to investigate the effect of a stabilized 10% weight loss on body composition, metabolic profile, and skeletal muscle gene expression profiling. DESIGN: Obese women were assigned to a 4-wk very-low-calorie diet, a 3-6-wk low-calorie diet, and a 4-wk weight-maintenance program to achieve a 10% weight loss. Resting energy expenditure, body composition, plasma variables, and skeletal muscle transcriptome were compared before weight loss and during stabilized weight reduction. RESULTS: Energy restriction caused an 11% weight loss. Stabilization to the new weight was accompanied by an 11% decrease in the resting metabolic rate normalized to the body cellular mass. A large number of genes were regulated with a narrow range of regulation. The main regulated genes were slow/oxidative fiber markers, which were overexpressed, and the gene encoding the glucose metabolism inhibitor PDK4, which tended to be down-regulated. The knowledge-based approach gene set enrichment analysis showed that a set of genes related to long-term calorie restriction was up-regulated, whereas sets of genes related to insulin, interleukin 6, and ubiquitin-mediated proteolysis were down regulated. CONCLUSIONS: Weight loss-induced decreases in resting metabolic rate persist after weight stabilization. Changes in skeletal muscle gene expression indicate a shift toward oxidative metabolism.

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