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85 results on '"MESH : Base Sequence"'

1. Comparative genomics of Mortierella elongata and its bacterial endosymbiont Mycoavidus cysteinexigens

Author: Du, C, Gryganskyi, G, Tschaplinski, R, Misztal, C, Wu, A, Desirò, I, Vande Pol, I, Du, R, Zienkiewicz, R, Zienkiewicz, G, Tisserant, R, Splivallo, G, Hainaut, R, Henrissat, R, Ohm, R., Kuo, G, Yan, G., Lipzen, G, Nolan, G, LaButti, G, Barry, G, Goldstein, G, Labbe, R., Schadt, R, Tuskan, G., Grigoriev, G, Martin, R, Vilgalys, R., Bonito, G., Du, J., Gryganskyi, A., Du, K., Tschaplinski, T., Misztal, K., Wu, S., Desirò, A., Vande Pol, N., Du, Z., Zienkiewicz, A., Zienkiewicz, K., Morin, E., Tisserant, E., Splivallo, R., Hainaut, M., Henrissat, B., Kuo, A., Yan, J., Lipzen, A., Nolan, M., LaButti, K., Barry, K., Goldstein, A., Labbé, J., Schadt, C., Grigoriev, I., Martin, F., Duke University [Durham], BioSciences Division [Oak Ridge], Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC-UT-Battelle, LLC, University of California [Berkeley], University of California, Arizona State University [Tempe] (ASU), Deparment of Plant, Soil and Microbial Sciences, Michigan State University [East Lansing], Michigan State University System-Michigan State University System, MSU-DOE Plant Research Laboratory and Department of Biochemistry and Molecular Biology, Interactions Arbres-Microorganismes (IAM), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Goethe-University Frankfurt am Main, Architecture et fonction des macromolécules biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Utrecht University [Utrecht], Genomic Science Program, U.S. Department of Energy, Office of Science - Biological and Environmental Research as part of the Plant Microbe Interfaces Scientific Focus Area at Oak Ridge National Laboratory, U.S. Department of Energy DE-AC05- 00OR22725, DOE Joint Genome Institute by the JGI Community sequencing program 570, Office of Science of the US Department of Energy DE-AC02-05CH11231, EU Laboratory of Excellence Advanced Research on the Biology of Tree and Forest Ecosystems (ARBRE) ANR-11-LABX-0002-01, Joint Genome Institute (JGI), Northwest Institute for Nonferrous Metal Research (NIN), Laboratorio de Turbulencia, Universidad de Santiago de Chile [Santiago] (USACH), UT-Battelle, LLC, Centre d'études de chimie métallurgique (CECM), Centre National de la Recherche Scientifique (CNRS), Kansas State University, Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), United States Department of Energy, Center for Human Genetics, University of Leuven School of Medicine, SCHOOL of MEDICINE [Louvain], Université Catholique de Louvain (UCL)-Université Catholique de Louvain (UCL), DOE Joint Genome Institute [Walnut Creek], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Sub Molecular Microbiology, Molecular Microbiology, Joint Genome Institute ( JGI ), Northwest Institute for Nonferrous Metal Research, Oak Ridge National Laboratory, Duke university [Durham], Centre d'études de chimie métallurgique ( CECM ), Centre National de la Recherche Scientifique ( CNRS ), Interactions Arbres-Microorganismes ( IAM ), Institut National de la Recherche Agronomique ( INRA ) -Université de Lorraine ( UL ), Architecture et fonction des macromolécules biologiques ( AFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ), UNIVERSITY of LEUVEN SCHOOL of MEDICINE, Institute of Northern Engineering, 455 Duckering Bldg, Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), 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 California [Berkeley] (UC Berkeley), and University of California (UC)
Subjects: Burkholderiaceae, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH : Symbiosis, MESH: Base Sequence, MESH: Genome, Bacterial, 2.2 Factors relating to physical environment, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, LAND PLANTS, 2.2 Factors relating to the physical environment, MESH : Metagenome, MESH: Animals, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Phylogeny, Phylogeny, MESH: Lipid Metabolism, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Symbiosis, Endosymbiosis, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Bacterial, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], FATTY-ACID BIOSYNTHESIS, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Fungal, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Genome, Fungal, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infection, Evolution, 030106 microbiology, MESH : Genome, Bacterial, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Microbiology, GENE-TRANSFER, 03 medical and health sciences, MESH : Burkholderiaceae, Botany, MESH : Evolution, Molecular, Ecology, Evolution, Behavior and Systematics, Comparative genomics, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, MESH : Genome, Fungal, Molecular, ENDOBACTERIA, MESH: Burkholderiaceae, DNA, 15. Life on land, Lipid Metabolism, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, INTRACELLULAR BACTERIA, 030104 developmental biology, MESH: Mortierella, Metagenome, MESH : Sequence Analysis, DNA, 0301 basic medicine, MESH: Sequence Analysis, DNA, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH: Carbohydrate Metabolism, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Genome, GUT MICROBIOME, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, ARBUSCULAR MYCORRHIZAL FUNGI, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Mortierella, MESH : Lipid Metabolism, MESH: Evolution, Molecular, 2. Zero hunger, Genetics, biology, Ecology, Fungal genetics, MESH : Carbohydrate Metabolism, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], ESCHERICHIA-COLI, Carbohydrate Metabolism, Sequence Analysis, Metabolic Networks and Pathways, CANDIDATUS GLOMERIBACTER GIGASPORARUM, Bacterial genome size, Symbiosis, Behavior and Systematics, Lipid biosynthesis, Animals, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Evolutionary Biology, Base Sequence, MESH : Metabolic Networks and Pathways, MESH : Phylogeny, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Metagenome, biology.organism_classification, MESH: Metabolic Networks and Pathways, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH : Base Sequence, BICOLOR S238N, MESH : Animals, MESH : Mortierella, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: International audience; Endosymbiosis of bacteria by eukaryotes is a defining feature of cellular evolution. In addition to well-known bacterial origins for mitochondria and chloroplasts, multiple origins of bacterial endosymbiosis are known within the cells of diverse animals, plants and fungi. Early-diverging lineages of terrestrial fungi harbor endosymbiotic bacteria belonging to the Burkholderiaceae. We sequenced the metagenome of the soil-inhabiting fungus Mortierella elongata and assembled the complete circular chromosome of its endosymbiont, Mycoavidus cysteinexigens, which we place within a lineage of endofungal symbionts that are sister clade to Burkholderia. The genome of M. elongata strain AG77 features a core set of primary metabolic pathways for degradation of simple carbohydrates and lipid biosynthesis, while the M. cysteinexigens (AG77) genome is reduced in size and function. Experiments using antibiotics to cure the endobacterium from the host demonstrate that the fungal host metabolism is highly modulated by presence/absence of M. cysteinexigens. Independent comparative phylogenomic analyses of fungal and bacterial genomes are consistent with an ancient origin for M. elongata - M. cysteinexigens symbiosis, most likely over 350 million years ago and concomitant with the terrestrialization of Earth and diversification of land fungi and plants.
Published: 2017

2. Binding of the Methyl Donor S -Adenosyl- <scp>l</scp> -Methionine to Middle East Respiratory Syndrome Coronavirus 2′- O -Methyltransferase nsp16 Promotes Recruitment of the Allosteric Activator nsp10

Author: Wahiba Aouadi, Bruno Canard, Alexandre Blanjoie, Jean-Jacques Vasseur, Françoise Debart, Etienne Decroly, Architecture et fonction des macromolécules biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Architecture et fonction des macromolécules biologiques ( AFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, S-Adenosylmethionine, Endoglycosidase, Adenosine, Methyltransferase, Viral Nonstructural Proteins, MESH: Base Sequence, MESH : Protein Multimerization, MESH: Allosteric Regulation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Bacteroides, MESH : Viral Nonstructural Proteins, Phylogeny, MESH : Methyltransferases, GacS, chemistry.chemical_classification, MESH: Kinetics, biology, MESH: Protein Multimerization, MESH : Protein Binding, Methylation, MESH : S-Adenosylmethionine, MESH : Allosteric Regulation, Genome Replication and Regulation of Viral Gene Expression, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, Biochemistry, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Middle East Respiratory Syndrome Coronavirus, RNA, Viral, MESH : Kinetics, Protein Binding, MESH : Adenosine, RNA virus, Immunology, Allosteric regulation, MESH : Middle East Respiratory Syndrome Coronavirus, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Microbiology, MESH: Methylation, Two-component system, 03 medical and health sciences, Allosteric Regulation, Pseudomonas, Virology, MESH: Methyltransferases, MESH : RNA, Viral, biochemistry, MESH: Protein Binding, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Binding site, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, Base Sequence, Protein, MESH: Middle East Respiratory Syndrome Coronavirus, Viral translation, MESH: S-Adenosylmethionine, RNA, Methyltransferases, MESH : Methylation, Glycoside hydrolase 39, MESH: Adenosine, biology.organism_classification, NMR, Kinetics, 030104 developmental biology, Enzyme, RNA processing, chemistry, Insect Science, MESH: Viral Nonstructural Proteins, MESH : Base Sequence, Protein Multimerization
Abstract: The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S -adenosyl- l -methionine (SAM)-dependent 2′- O -methyltransferase (2′-O-MTase) that is thought to methylate the ribose 2′-OH of the first transcribed nucleotide (N 1 ) of viral RNA cap structures. This 2′-O-MTase activity is regulated by nsp10. The 2′- O methylation prevents virus detection by cell innate immunity mechanisms and viral translation inhibition by the interferon-stimulated IFIT-1 protein. To unravel the regulation of nsp10/nsp16 2′-O-MTase activity, we used purified MERS-CoV nsp16 and nsp10. First, we showed that nsp16 recruited N7-methylated capped RNA and SAM. The SAM binding promotes the assembly of the enzymatically active nsp10/nsp16 complex that converted 7m GpppG (cap-0) into 7m GpppG 2′Om (cap-1) RNA by 2′-OH methylation of N 1 in a SAM-dependent manner. The subsequent release of SAH speeds up nsp10/nsp16 dissociation that stimulates the reaction turnover. Alanine mutagenesis and RNA binding assays allowed the identification of the nsp16 residues involved in RNA recognition forming the RNA binding groove (K46, K170, E203, D133, R38, Y47, and Y181) and the cap-0 binding site (Y30, Y132, and H174). Finally, we found that nsp10/nsp16 2′-O-MTase activity is sensitive to known MTase inhibitors, such as sinefungin and cap analogues. This characterization of the MERS-CoV 2′-O-MTase is a preliminary step toward the development of molecules to inhibit cap 2′-O methylation and to restore the host antiviral response. IMPORTANCE MERS-CoV codes for a cap 2′- O -methyltransferase that converts cap-0 into cap-1 structure in order to prevent virus detection by cell innate immunity mechanisms. We report the biochemical properties of MERS-CoV 2′O-methyltransferase, which is stimulated by nsp10 acting as an allosteric activator of the nsp16 2′- O -methyltransferase possibly through enhanced RNA binding affinity. In addition, we show that SAM promotes the formation of the active nsp10/nsp16 complex. Conversely, after cap methylation, the reaction turnover is speeded up by cap-1 RNA release and nsp10/nsp16 complex dissociation, at the low intracellular SAH concentration. These results suggest that SAM/SAH balance is a regulator of the 2′- O -methyltransferase activity and raises the possibility that SAH hydrolase inhibitors might interfere with CoV replication cycle. The enzymatic and RNA binding assays developed in this work were also used to identify nsp16 residues involved in cap-0 RNA recognition and to understand the action mode of known methyltransferase inhibitors.
Published: 2017

3. EWET: Data collection and interface for the genetic analysis of Echinococcus multilocularis based on EmsB microsatellite

Author: Raphael Mélior, Jérémy Navion, Vanessa Hormaz, Laurence Millon, Francis Raoul, Jonathan Brillaud, Jenny Knapp, Jean Daniel Tissot, Sylvie Damy, Gérald Umhang, Eve Afonso, Adriano Casulli, Frédéric Dadeau, Bruno Gottstein, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), UMS THETA (terre, homme, environnement, temps, astronomie) ( OSU-THETA ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux ( MSHE ), Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'environnement et du Travail ( ANSES ), ANSES, Institute of Parasitology, University of Bern, Laboratoire de la rage et pathologie des animaux sauvages ( LERPAS ), Istituto Superiore di Sanità Rome, Rome, Italy, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Service de parasitologie et mycologie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), OSU-THETA - Observatoire des Sciences de l'Univers - Terre Homme Environnement Temps Astronomie (OSU-THETA), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux (MSHE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de la rage et pathologie des animaux sauvages (LERPAS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Service de parasitologie et mycologie [CHRU de Besançon], and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: 0301 basic medicine, Epidemiology, Flatworms, lcsh:Medicine, Artificial Gene Amplification and Extension, MESH: Base Sequence, MESH: Genetic Markers, MESH : Echinococcus multilocularis, MESH : Microsatellite Repeats, Polymerase Chain Reaction, Computer Applications, 0302 clinical medicine, Databases, Genetic, MESH : Genes, Helminth, Medicine and Health Sciences, MESH : Genetic Markers, MESH: Animals, MESH: Genetic Variation, lcsh:Science, 610 Medicine & health, Genes, Helminth, MESH: Databases, Genetic, Data Management, Biological data, Multidisciplinary, Geography, 630 Agriculture, Eukaryota, Phylogeography, Biogeography, Genetic Epidemiology, Calibration, Web-Based Applications, Microsatellite, Research Article, Genetic Markers, Genotyping, Computer and Information Sciences, 030231 tropical medicine, Biology, Research and Analysis Methods, Echinococcus multilocularis, MESH: Calibration, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, MESH : Genetic Variation, Helminths, Genetic variation, Genetics, Parasitic Diseases, Animals, Molecular Biology Techniques, MESH : Databases, Genetic, Molecular Biology, MESH : Calibration, MESH: Echinococcus multilocularis, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Evolutionary Biology, Genetic diversity, Base Sequence, Population Biology, Ecology and Environmental Sciences, lcsh:R, Organisms, Genetic Variation, Biology and Life Sciences, biology.organism_classification, Invertebrates, Echinococcus, 030104 developmental biology, Genetic distance, Evolutionary biology, Earth Sciences, 570 Life sciences, biology, lcsh:Q, MESH : Base Sequence, MESH: Microsatellite Repeats, MESH : Animals, Population Genetics, Microsatellite Repeats, MESH: Genes, Helminth
Abstract: International audience; Evolution and dispersion history on Earth of organisms can best be studied through biological markers in molecular epidemiological studies. The biological diversity of the cestode Echinococcus multilocularis was investigated in different cladistic approaches. First the morphological aspects were explored in connection with its ecology. More recently, molecular aspects were investigated to better understand the nature of the variations observed among isolates. The study of the tandemly repeated multilocus microsatellite EmsB allowed us to attain a high genetic diversity level where other classic markers have failed. Since 2006, EmsB data have been collected on specimens from various endemic foci of the parasite in Europe (in historic and newly endemic areas), Asia (China, Japan and Kyrgyzstan), and North America (Canada and Alaska). Biological data on the isolates and metadata were also recorded (e.g. host, geographical location, EmsB analysis, citation in the literature). In order to make available the data set of 1,166 isolates from classic and aberrant domestic and wild animal hosts (larval lesions and adult worms) and from human origin, an open web access interface, developed in PHP, and connected to a PostgreSQL database, was developed in the EmsB Website for the Echinococcus Typing (EWET) project. It allows researchers to access data collection, perform genetic analyses online (e.g. defining the genetic distance between their own samples and the samples in the database), consult distribution maps of EmsB profiles, and record and share their new EmsB genotyping data. In order to standardize the EmsB analyses performed in the different laboratories throughout the world, a calibrator was developed. The final aim of this project was to gather and arrange available data to permit to better understand the dispersion and transmission patterns of the parasite among definitive and intermediate hosts, in order to organize control strategies on the ground.
Published: 2017
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4. Genome sequence of Aedes aegypti, a major arbovirus vector

Author: Sergio Verjovski-Almeida, James E. Galagan, Ryan C. Kennedy, Zhiyong Xi, Jason R. Miller, Eric Eisenstadt, Kyanne R. Reidenbach, Robert V. Bruggner, Yu-Hui Rogers, Hadi Quesneville, Doreen Werner, Owen White, Alexander S. Raikhel, Mario Stanke, J. Spencer Johnston, Diane D. Lovin, Evgenia V. Kriventseva, Ian T. Paulsen, Kathryn S. Campbell, Norman H. Lee, Ewan Birney, Karyn Megy, Hean Koo, David Kulp, Shelby L. Bidwell, Jingsong Zhu, Philip Montgomery, Paolo Amedeo, Yongmei Zhao, Chinnappa D. Kodira, Javier Costas, Michael C. Schatz, Steven P. Sinkins, Claire M. Fraser-Liggett, Martin Shumway, Kurt LaButti, Akio Mori, Brendan J. Loftus, Manfred Grabherr, Eric O. Stinson, Frank H. Collins, Zhijian Jake Tu, Monique R. Coy, Matt Crawford, Janice P. Vanzee, William M. Gelbart, Joshua Orvis, Peter Arensburger, Chunhong Mao, Evgeny M. Zdobnov, Saul A. Kravitz, Suely Lopes Gomes, David DeCaprio, David G. Hogenkamp, Daniel Lawson, Dennis L. Knudson, David W. Severson, George Dimopoulos, Marcelo B. Soares, Sinéad B. O'Leary, Peter W. Atkinson, David M. Jaffe, Becky deBruyn, Martin Hammond, Ana L. T. O. Nascimento, Jim Biedler, Stefan Wyder, Jose M. C. Tubio, Bruce W. Birren, Catherine A. Hill, Chad Nusbaum, Eduardo Lee, Song Li, Susan E. Brown, Jennifer R. Wortman, James R. Hogan, Hamza El-Dorry, Qi Zhao, Linda Hannick, Carlos Frederico Martins Menck, Vishvanath Nene, Jonathan Crabtree, Steven L. Salzberg, Michael H. Holmes, Maria de Fatima Bonaldo, Quinghu Ren, Mihaela Pertea, Charles Roth, Evan Mauceli, Karin Eiglmeier, Horacio Naveira, Brian J. Haas, Qiandong Zeng, Neil F. Lobo, Jennifer R. Schneider, The Institute for Genomic Research, The Institute for Genomic Research, Rockville, European Bioinformatics Institute [Hinxton] ( EMBL-EBI ), European Molecular Biology Laboratory [Hinxton], Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Broad Institute of MIT and Harvard, Virginia Polytechnic Institute and State University [Blacksburg], University College Dublin [Dublin] ( UCD ), Bloomberg School of Public Health, Johns Hopkins University ( JHU ) -Bloomberg School of Public Health, University of Geneva Medical School, Swiss Institute of Bioinformatics-University of Geneva Medical School, University of Notre Dame ( UND ), Harvard University [Cambridge], College of Agricultural Sciences Colorado State University, Colorado State University [Fort Collins] ( CSU ) -College of Agricultural Sciences, Northwestern University [Evanston], University of California [Riverside] ( UCR ), Department of Atmospheric, Oceanic and Planetary Physics [Oxford] ( AOPP ), University of Oxford [Oxford], Purdue University [West Lafayette], Centro Nacional de Genotipado Fundación Pública Galega de Medicina Xenómica Hospital Clínico Universitario de Santiago, Centro Nacional de Genotipado-Fundación Pública Galega de Medicina Xenómica-Hospital Clínico Universitario de Santiago, Institut Pasteur [Paris], Universidade de Sao Paulo Instituto de Quimica, Universidade de São Paulo ( USP ) -Instituto de Quimica, Texas A&M University [College Station], Joint Technology Center, University of Massachusetts [Amherst] ( UMass Amherst ), Universidade de Sao Paulo, Institute of Biomedical Sciences, Universidade de São Paulo ( USP ) -Institute of Biomedical Sciences, Instituto Butantan [São Paulo], Universidade da Coruña, University of Maryland [College Park], Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), University of California [Santa Cruz] ( UCSC ), Complexo Hospitalario Universitario de Santiago, Universität Göttingen, Georg-August-Universität Göttingen, George Washington University Medical Center, George Washington University ( GW ), The Institute for Genomic Research (TIGR), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University College Dublin [Dublin] (UCD), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL)-University of Geneva Medical School, University of Notre Dame [Indiana] (UND), Colorado State University [Fort Collins] (CSU)-College of Agricultural Sciences, University of California [Riverside] (UCR), University of California, Department of Atmospheric, Oceanic and Planetary Physics [Oxford] (AOPP), Universidade de São Paulo (USP)-Instituto de Quimica, University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS), Universidade de São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo (USP), University of Maryland System, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of California [Santa Cruz] (UCSC), Georg-August-University [Göttingen], The George Washington University (GW), George Washington University (GW), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL)-University of Geneva Medical School, Harvard University, University of California [Riverside] (UC Riverside), University of California (UC), University of Oxford, Institut Pasteur [Paris] (IP), Universidade de São Paulo = University of São Paulo (USP)-Instituto de Quimica, Universidade de São Paulo = University of São Paulo (USP)-Institute of Biomedical Sciences (ICB/USP), Universidade de São Paulo = University of São Paulo (USP), University of California [Santa Cruz] (UC Santa Cruz), Georg-August-University = Georg-August-Universität Göttingen, Zdobnov, Evgeny, and Wyder, Stefan
Subjects: 0106 biological sciences, Male, Transcription, Genetic, Genome, Insect, transposons, receptors, Genes, Insect, Aedes/ genetics/metabolism, MESH: Genes, Insect, Yellow Fever/prevention & control/transmission, MESH: Base Sequence, 01 natural sciences, Dengue/prevention & control/transmission, MESH: Protein Structure, Tertiary, MESH: Arboviruses, MESH : Insect Vectors, MESH: Insect Proteins, MESH : Anopheles gambiae, MESH: Animals, MESH : Arboviruses, insects, MESH: Yellow Fever, superfamily, ddc:616, 0303 health sciences, Anopheles, MESH : Genes, Insect, 3. Good health, yellow-fever mosquito, anopheles-gambiae, drosophila-melanogaster, expression, evolution, organization, Drosophila melanogaster, MESH: DNA Transposable Elements, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Multigene Family, Public Health, MESH : Protein Structure, Tertiary, MESH: Sex Characteristics, Molecular Sequence Data, MESH : Multigene Family, MESH: Sex Determination (Genetics), MESH : Sex Determination (Genetics), Arbovirus, Article, 03 medical and health sciences, Species Specificity, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Anopheles gambiae, Yellow Fever, MESH: Species Specificity, Humans, MESH: Humans, MESH: Molecular Sequence Data, fungi, MESH : Humans, MESH : Sex Characteristics, Membrane Transport Proteins, Sex Determination Processes, medicine.disease, Insect Vectors, Protein Structure, Tertiary, Sex Determination (Genetics), MESH: Multigene Family, MESH: Female, MESH : Sequence Analysis, DNA, MESH: Sequence Analysis, DNA, Drosophila melanogaster/genetics, MESH : Molecular Sequence Data, Odorant binding, Insect Proteins/genetics, Anopheles gambiae, MESH: Dengue, Genome, MESH: Membrane Transport Proteins, Dengue, MESH : Membrane Transport Proteins, Aedes, Insect Vectors/ genetics/metabolism, MESH : Drosophila melanogaster, MESH : Female, Membrane Transport Proteins/genetics, Genetics, MESH : Insect Proteins, Sex Characteristics, Multidisciplinary, MESH: Synteny, MESH: Aedes, MESH : Genome, Insect, MESH : DNA Transposable Elements, Insect Proteins, Female, Orthologous Gene, MESH : Male, MESH : Dengue, Aedes aegypti, MESH: Insect Vectors, Biology, 010603 evolutionary biology, Synteny, MESH: Drosophila melanogaster, Protein Structure, Tertiary/genetics, MESH : Yellow Fever, parasitic diseases, medicine, MESH : Species Specificity, Animals, 030304 developmental biology, MESH : Aedes, Base Sequence, MESH: Genome, Insect, MESH: Transcription, Genetic, MESH : Synteny, MESH : Transcription, Genetic, Sequence Analysis, DNA, biology.organism_classification, MESH: Male, DNA Transposable Elements, MESH : Base Sequence, MESH : Animals, Arboviruses, Anopheles gambiae/genetics/metabolism
Abstract: We present a draft sequence of the genome of Aedes aegypti , the primary vector for yellow fever and dengue fever, which at ∼1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae . Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of ∼4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster . Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of ∼2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
Published: 2016

5. Evidence for the negative regulation of phytase gene expression in Streptomyces lividans and Streptomyces coelicolor

Author: Boukhris, Ines, Dulermo, Thierry, Chouayekh, Hichem, Virolle, Marie-Joëlle, Centre de Biotechnologie de Sfax ( CBS ), 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 ), Centre de Biotechnologie de Sfax (CBS), Institut de Biologie Intégrative de la Cellule (I2BC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Operon, [SDV]Life Sciences [q-bio], MESH: Base Sequence, MESH : Promoter Regions, Genetic, MESH : Glucuronidase, MESH: Glucuronidase, MESH : Bacterial Proteins, MESH: 6-Phytase, MESH : Streptomyces coelicolor, Promoter Regions, Genetic, MESH: Bacterial Proteins, Soil Microbiology, Glucuronidase, Sequence Deletion, 6-Phytase, MESH: Gene Expression Regulation, Bacterial, MESH : Protein Binding, MESH: Sequence Deletion, Negative, Protein Binding, MESH : Gene Expression Regulation, Bacterial, MESH: Operon, Phytic Acid, MESH : Soil Microbiology, MESH: Streptomyces lividans, Streptomyces coelicolor, Beta-glucuronidase reporter gene, Bacterial Proteins, PHO box, PhoR, PhoP, Operon, MESH: Promoter Regions, Genetic, MESH: Protein Binding, MESH: Phytic Acid, Repetitive Sequences, Nucleic Acid, MESH : Streptomyces lividans, MESH: Repetitive Sequences, Nucleic Acid, Base Sequence, [ SDV ] Life Sciences [q-bio], MESH : 6-Phytase, MESH : Sequence Deletion, Gene Expression Regulation, Bacterial, MESH: Streptomyces coelicolor, MESH : Repetitive Sequences, Nucleic Acid, MESH : Phytic Acid, MESH: Soil Microbiology, Streptomyces lividans, MESH : Base Sequence, Streptomyces phytase, Positive regulation, Phosphate limitation
Abstract: International audience; Sco7697, a gene encoding a phytase, enzyme able to degrade phytate (myo-inositol 1,2,3,4,5,6-hexakis phosphate), the most abundant phosphorus storing compound in plants is present in the genome of S. coelicolor, a soil born bacteria with a saprophytic lifestyle. The expression of this gene was previously shown to be induced in conditions of Pi limitation by the response regulator PhoP binding to an operator sequence, the PHO box, located upstream of the -35 promoter sequence. A close examination of the promoter region of sco7697 revealed the presence of another putative operator site, a Direct Repeat (DR), located downstream of the -10 promoter sequence. In order to determine whether this DR played a role in regulation of sco7697 expression, different variants of the phytase gene promoter region were transcriptionally fused to the ß-glucuronidase reporter gene (GUS). As expected, deletion of the PHO box led to abolition of sco7697 induction in conditions of Pi limitation. Interestingly, alteration of the DR correlated with a dramatic increase of GUS expression but only when PhoP was present. These results demonstrated that this DR is the site of strong negative regulation by an unknown repressor. The latter would impede the necessary activation of phytase expression by PhoP.
Published: 2016

6. Characterization of Unique Signature Sequences in the Divergent Maternal Protein Bcl2l10

Author: Germain Gillet, Abdel Aouacheria, François Penin, Aurélie Cornut-Thibaut, Yannis Guillemin, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS 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 National de la Recherche Scientifique (CNRS), Ganivet, Agnès, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), 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 ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS 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 National de la Recherche Scientifique ( CNRS ), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, Amino Acid Motifs, MESH: Amino Acid Sequence, MESH: Base Sequence, MESH : Proto-Oncogene Proteins c-bcl-2, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: INDEL Mutation, protein sequence, MESH: Amino Acid Motifs, MESH: Protein Structure, Tertiary, 0302 clinical medicine, INDEL Mutation, Databases, Genetic, genetic polymorphism, MESH : Female, MESH: Animals, MESH: Genetic Variation, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Peptide sequence, MESH: Databases, Genetic, MESH: Evolution, Molecular, Sequence Deletion, Genetics, chemistry.chemical_classification, 0303 health sciences, MESH : Amino Acid Sequence, MESH : Sequence Alignment, apoptosis, Vertebrate, MESH: Sequence Deletion, Amino acid, Proto-Oncogene Proteins c-bcl-2, MESH: Calcium, 030220 oncology & carcinogenesis, Female, MESH : Protein Structure, Tertiary, MESH : Amino Acid Motifs, Molecular Sequence Data, MESH: Sequence Alignment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sequence alignment, Biology, Cell Line, MESH: Oocytes, Evolution, Molecular, 03 medical and health sciences, Bcl-2 family, MESH : Genetic Variation, biology.animal, evolution, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Genetic variation, Homologous chromosome, Animals, Humans, MESH : HeLa Cells, MESH : Evolution, Molecular, Amino Acid Sequence, MESH : Calcium, MESH : Databases, Genetic, Indel, MESH : INDEL Mutation, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH : Mutagenesis, Insertional, calcium, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Sequence Deletion, MESH: Apoptosis, MESH : Humans, MESH : Oocytes, Genetic Variation, Protein Structure, Tertiary, MESH: Cell Line, Mutagenesis, Insertional, MESH: Mutagenesis, Insertional, MESH: Proto-Oncogene Proteins c-bcl-2, chemistry, MESH: HeLa Cells, Oocytes, MESH : Base Sequence, MESH : Animals, Sequence Alignment, MESH: Female, MESH : Apoptosis, HeLa Cells
Abstract: International audience; Insertions or deletions (indels) of amino acids residues have been recognized as an important source of genetic and structural divergence between paralogous Bcl-2 family members. However, these signature sequences have not so far been extensively investigated amongst orthologous Bcl-2 family proteins. Bcl2l10 is an antiapoptotic member of the Bcl-2 family that has evolved rapidly throughout the vertebrate lineage and which shows conserved abundant expression in eggs and oocytes. In this paper, we have unraveled two major sites of divergence between human Bcl2l10 and its vertebrate homologs. The first one provides length variation at the N-terminus (before the BH4 domain) and the second one is located between the predicted α5-α6 pore-forming helices, providing an unprecedented case in the superfamily of helix-bundled pore-forming proteins. These two particular indels were studied phylogenetically and through biochemical and cell biological techniques, including truncation and site-directed mutagenesis. While deletion of the N-terminal extension had no significant functional impact in HeLa cells, our results suggest that the human Bcl2l10 protein evolved a calcium-binding motif in its α5-α6 interhelical region by acquiring critical negatively charged residues. Considering the reliance of female eggs on calcium-dependent proteins and calcium-regulated processes and the exceptional longevity of oocytes in the primate lineage, we propose that this microstructural variation may be an adaptive feature associated with high maternal expression of this Bcl-2 family member.
Published: 2011

7. Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas. : Activating STAT3 mutations in hepatocellular adenoma

Author: Jeanne Tran Van Nhieu, Michel Bihl, Karine Poussin, Mohamed Amessou, Paulette Bioulac-Sage, Jessica Zucman-Rossi, Charles Balabaud, Camilla Pilati, Jean-Charles Nault, Tina Izard, Valérie Paradis, Gabrielle Couchy, Genomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Labex Immuno-oncology, Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Department of Cancer Biology, The Scripps Research Institute, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hépato-Gastro Entérologie et Oncologie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), and This work was supported by the association pour la recherche Contre le Cancer (ARC, grant n°3194), Inserm (Réseaux de recherche clinique et réseaux de recherche en santé des populations), Collection Nationale des Carcinomes Hépatocellulaires, the Ligue Nationale Contre le Cancer ('Cartes d'identité des tumeurs' program) and the BioIntelligence collaborative program. C.P., M.A. and J-C.N. are supported by a fellowship from the MENRT, Inca and ARC, respectively. T.I. is supported by the National Institutes of Health grants GM071596, AI055894, and AI067949.
Subjects: MESH : Tyrosine, Male, Models, Molecular, MESH : Liver Neoplasms, MESH : Mutant Proteins, MESH : Aged, MESH : RNA, Small Interfering, SH2 domain, medicine.disease_cause, HNF1A, STAT3, MESH : Phosphorylation, 0302 clinical medicine, MESH : STAT3 Transcription Factor, Cytokine Receptor gp130, Immunology and Allergy, CTNNB1, MESH : Female, SOCS3, Phosphorylation, RNA, Small Interfering, 0303 health sciences, Mutation, Liver Neoplasms, DNA, Neoplasm, MESH : Adult, Middle Aged, SAA, 3. Good health, MESH : Cytokine Receptor gp130, JAK1, src-Family Kinases, JAK2, MESH : Dimerization, 030220 oncology & carcinogenesis, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Female, MESH : DNA, Neoplasm, MESH : Mutation, CRP, IL6ST, Dimerization, Tyrosine kinase, Src, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src, MESH : Carcinoma, Hepatocellular, Adult, STAT3 Transcription Factor, Carcinoma, Hepatocellular, MESH : Interleukin-6, MESH : Models, Molecular, MESH : Male, Immunology, Active Transport, Cell Nucleus, Biology, IFN, Adenoma, Liver Cell, gp130, 03 medical and health sciences, MESH : Adenoma, Liver Cell, MESH : Protein Structure, Quaternary, Cell Line, Tumor, medicine, Humans, MESH : Middle Aged, Protein Structure, Quaternary, MESH : Active Transport, Cell Nucleus, Aged, 030304 developmental biology, MESH : Signal Transduction, IL-6, Base Sequence, MESH : Cell Line, Tumor, Interleukin-6, MESH : Humans, Brief Definitive Report, beta-catenin, digestive system diseases, STAT protein, Inflammatory Hepatocellular Adenoma, Cancer research, Tyrosine, MESH : src-Family Kinases, MESH : Base Sequence, Mutant Proteins, Carcinogenesis
Abstract: Somatic STAT3 mutations present in a subset of inflammatory hepatocellular adenomas result in the generation of constitutively active STAT3 proteins that homodimerize independently of IL-6 stimulation., Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumors. 60% of these tumors have IL-6 signal transducer (IL6ST; gp130) mutations that activate interleukin 6 (IL-6) signaling. Here, we report that 12% of IHCA subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49). Most of these mutations are amino acid substitutions in the SH2 domain that directs STAT3 dimerization. In contrast to wild-type STAT3, IHCA STAT3 mutants constitutively activated the IL-6 signaling pathway independent of ligand in hepatocellular cells. Indeed, the IHCA STAT3 Y640 mutant homodimerized independent of IL-6 and was hypersensitive to IL-6 stimulation. This was associated with phosphorylation of tyrosine 705, a residue required for IL-6–induced STAT3 activation. Silencing or inhibiting the tyrosine kinases JAK1 or Src, which phosphorylate STAT3, impaired constitutive activity of IHCA STAT3 mutants in hepatocellular cells. Thus, we identified for the first time somatic STAT3 mutations in human tumors, revealing a new mechanism of recurrent STAT3 activation and underscoring the role of the IL-6–STAT3 pathway in benign hepatocellular tumorigenesis.
Published: 2011

8. Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake

Author: Fabien Zoulim, Marie-Pierre Lambert, Massimo Tommasino, Zdenko Herceg, Jörg Tost, Jean-Yves Scoazec, Anupam Paliwal, Pierre Hainaut, Thomas Vaissière, Bakary S. Sylla, Isabelle Chemin, Centre de Recherche en Cancérologie de Lyon (CRCL), 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 National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), International Agency for Cancer Research (IACR), Equipe 16, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Service d'hépatologie et de gastroentérologie, Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (CRCL), 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), Sect Mech Carcinogenesis, equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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 ), Interactions Bactéries-Cellules ( UIBC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), International Agency for Cancer Research ( IACR ), International Agency for Cancer Research, 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 ) -Université Claude Bernard Lyon 1 ( UCBL ), Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Hospices Civils de Lyon ( HCL ) -Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer ( CIRC - IARC ), Organisation mondiale de la santé (OMS/WHO), international Agency for Research on Cancer - IARC, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), 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), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Hospices Civils de Lyon (HCL)-Hôtel-Dieu-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), and Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH : Liver Neoplasms, MESH : Aged, Receptors, Nicotinic, MESH: Base Sequence, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: DNA Methylation, 0302 clinical medicine, Risk Factors, MESH: Liver Neoplasms, MESH: Risk Factors, MESH : Female, MESH: Gene Silencing, MESH: Carcinoma, Hepatocellular, MESH: Glutathione S-Transferase pi, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Tumor Suppressor Proteins, Liver Neoplasms, RNA-Binding Proteins, DNA, Neoplasm, Hepatitis C, Methylation, Middle Aged, MESH : Adult, Hepatitis B, MESH : Risk Factors, 3. Good health, DNA-Binding Proteins, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, DNA methylation, MESH: Receptors, Nicotinic, Female, MESH : DNA Primers, MESH : DNA, Neoplasm, MESH : DNA-Binding Proteins, Adult, MESH : Carcinoma, Hepatocellular, MESH: DNA Primers, Carcinoma, Hepatocellular, Alcohol Drinking, MESH : Male, Hepatitis C virus, MESH : RNA-Binding Proteins, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, 03 medical and health sciences, MESH : Gene Silencing, medicine, Humans, MESH : Middle Aged, MESH: Tumor Suppressor Proteins, Gene Silencing, neoplasms, Aged, DNA Primers, 030304 developmental biology, MESH: Hepatitis C, Hepatitis B virus, MESH: Humans, Base Sequence, MESH : Receptors, Nicotinic, MESH: Hepatitis B, Hepatology, Tumor Suppressor Proteins, MESH : Humans, MESH : Hepatitis B, Cancer, MESH: Adult, DNA Methylation, MESH : Hepatitis C, Phosphoproteins, medicine.disease, MESH: Male, digestive system diseases, MESH : Alcohol Drinking, MESH: RNA-Binding Proteins, Glutathione S-Transferase pi, MESH : Glutathione S-Transferase pi, Immunology, MESH : Base Sequence, MESH : Phosphoproteins, MESH : DNA Methylation, MESH: Female, MESH: Alcohol Drinking, MESH: DNA-Binding Proteins
Abstract: International audience; BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most frequent human cancers and a major cause of cancer-related death worldwide. The major risk factors for developing HCC are infection by hepatitis B virus (HBV) and hepatitis C virus (HCV), chronic alcoholism, and aflatoxins; however, critical gene targets remain largely unknown. Herein, we sought to establish DNA methylation patterns in HCC and corresponding cirrhotic tissues and to identify DNA methylation changes associated with major risk factors. METHODS: We have established assays for quantitative analysis of DNA methylation levels in a panel of seven cancer-associated genes and repetitive elements, and combined these assays with a series of HCC tumors, associated with major risk factors, collected from two different geographical areas. RESULTS: We found a high frequency of aberrant hypermethylation of specific genes (RASSF1A, GSTP1, CHRNA3, and DOK1) in HCC tumors as compared to control cirrhotic or normal liver tissues, suggesting that aberrant hypermethylation exhibits non-random and tumor-specific patterns in HCC. Importantly, our analysis revealed an association between alcohol intake and the hypomethylation of MGMT and between hypermethylation of GSTP1 and HBV infection, indicating that hypermethylation of the genes analyzed in HCC tumors exhibits remarkably distinct patterns depending on associated risk factors. CONCLUSIONS: This study identifies aberrant DNA methylation of specific cellular genes in HCC and the major risk factors associated with these changes, providing information that could be exploited for biomarker discovery in clinics and molecular epidemiology.
Published: 2011

9. Murine APOBEC1 Is a Powerful Mutator of Retroviral and Cellular RNA In Vitro and In Vivo

Author: Denise Guetard, Marc Sitbon, Jean-Pierre Vartanian, Anne Keriel, Myrtille Renard, Simon Wain-Hobson, Vincent Petit, Rétrovirologie Moléculaire, Institut Pasteur [Paris]-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 Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Hypoxanthine Phosphoribosyltransferase, MESH : Molecular Sequence Data, MESH : RNA, Messenger, MESH : DNA, Complementary, MESH : NIH 3T3 Cells, viruses, Muscle Proteins, MESH: Base Sequence, Nucleic Acid Denaturation, MESH : Retroviridae Infections, MESH: Animals, Newborn, Mice, chemistry.chemical_compound, MESH : Hypoxanthine Phosphoribosyltransferase, Structural Biology, Murine leukemia virus, MESH : RNA, MESH: Animals, APOBEC Deaminases, MESH : Cytidine Deaminase, Gammaretrovirus, MESH : Muscle Proteins, 0303 health sciences, biology, Nucleotides, MESH : Animals, Newborn, 030302 biochemistry & molecular biology, MESH: Leukemia Virus, Murine, Cytidine, Cytidine deaminase, MESH: Apolipoproteins B, 3. Good health, Leukemia Virus, Murine, MESH: Retroviridae Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH : Mutation, MESH: Genome, Viral, MESH : Genome, Viral, MESH : Leukemia Virus, Murine, MESH : Nucleic Acid Denaturation, APOBEC, DNA, Complementary, MESH: Mutation, APOBEC-1 Deaminase, Molecular Sequence Data, MESH: Leukemia, Experimental, Genome, Viral, MESH: Nucleic Acid Denaturation, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Muscle Proteins, 03 medical and health sciences, MESH: RNA, Cytidine Deaminase, MESH : Mice, MESH : RNA Editing, Animals, Humans, MESH: RNA Editing, RNA, Messenger, MESH: Mice, Molecular Biology, Apolipoproteins B, MESH: RNA, Messenger, MESH: Cytidine Deaminase, 030304 developmental biology, Messenger RNA, Leukemia, Experimental, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, APOBEC1, MESH : Humans, MESH: Tumor Virus Infections, RNA, MESH : Apolipoproteins B, MESH: DNA, Complementary, biology.organism_classification, MESH: Hypoxanthine Phosphoribosyltransferase, Molecular biology, MESH: Nucleotides, Tumor Virus Infections, Animals, Newborn, chemistry, Mutation, NIH 3T3 Cells, MESH : Nucleotides, MESH : Leukemia, Experimental, MESH : Base Sequence, MESH : Animals, RNA Editing, MESH : Tumor Virus Infections, Retroviridae Infections, MESH: NIH 3T3 Cells
Abstract: International audience; Mammalian APOBEC molecules comprise a large family of cytidine deaminases with specificity for RNA and single-stranded DNA (ssDNA). APOBEC1s are invariably highly specific and edit a single residue in a cellular mRNA, while the cellular targets for APOBEC3s are not clearly established, although they may curtail the transposition of some retrotransposons. Two of the seven member human APOBEC3 enzymes strongly restrict human immunodeficiency virus type 1 in vitro and in vivo. We show here that ssDNA hyperediting of an infectious exogenous gammaretrovirus, the Friend-murine leukemia virus, by murine APOBEC1 and APOBEC3 deaminases occurs in vitro. Murine APOBEC1 was able to hyperdeaminate cytidine residues in murine leukemia virus genomic RNA as well. Analysis of the edited sites shows that the deamination in vivo was due to mouse APOBEC1 rather than APOBEC3. Furthermore, murine APOBEC1 is able to hyperedit its primary substrate in vivo, the apolipoprotein B mRNA, and a variety of heterologous RNAs. In short, murine APOBEC1 is a hypermutator of both RNA and ssDNA in vivo, which could exert occasional side effects upon overexpression.
Published: 2009

10. Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor

Author: Marc Stern, Marie-Hélène Delfau-Larue, Hervé Mal, Diane Damotte, Magali Colombat, Michel Fournier, Patrice Callard, Jacques Diebold, Jean-Pierre Farcet, Christiane Copie-Bergman, Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de pneumologie B, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service d'anatomie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service d'immunologie biologique, Service de pneumologie, and Hôpital Foch [Suresnes]
Subjects: Lung Diseases, Pathology, MESH : Molecular Sequence Data, MESH : DNA, medicine.medical_treatment, Immunoglobulin Variable Region, Paraproteinemias, MESH : Immunoglobulin Heavy Chains, Plasma cell, Biochemistry, 0302 clinical medicine, MESH : Female, MESH : Immunoglobulin Variable Region, B-Lymphocytes, 0303 health sciences, MESH : Lung Diseases, Cysts, MESH : Amino Acid Sequence, Hematology, MESH : Adult, MESH : Immunoglobulin Light Chains, 3. Good health, medicine.anatomical_structure, MESH : Paraproteinemias, 030220 oncology & carcinogenesis, MESH : Lung Transplantation, Female, Genes, Immunoglobulin Light Chain, Immunoglobulin Heavy Chains, Lung Transplantation, Adult, medicine.medical_specialty, Genes, Immunoglobulin Heavy Chain, Molecular Sequence Data, Immunology, MESH : Genes, Immunoglobulin Heavy Chain, MESH : Cysts, Biology, Immunoglobulin light chain, Article, Light chain deposition disease, MESH : B-Lymphocytes, Lung Disorder, Immunoglobulin kappa-Chains, 03 medical and health sciences, MESH : Immunoglobulin kappa-Chains, medicine, Humans, Lung transplantation, Amino Acid Sequence, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Genes, Immunoglobulin Light Chain, 030304 developmental biology, Lung, Base Sequence, MESH : Humans, DNA, Cell Biology, medicine.disease, Immunoglobulin heavy chain, MESH : Base Sequence, Immunoglobulin Light Chains, CD5
Abstract: We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum-free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in 3 patients with cystic lung LCDD. Histologic examination of the explanted lungs showed diffuse nonamyloid κ light chain deposits associated with a mild lymphoid infiltrate composed of aggregates of small CD20+, CD5−, CD10− B lymphocytes reminiscent of bronchus-associated lymphoid tissue. Using polymerase chain reaction (PCR), we identified a dominant B-cell clone in the lung in the 3 studied patients. The clonal expansion of each patient shared an unmutated antigen receptor variable region sequence characterized by the use of IGHV4-34 and IGKV1 subgroups with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biologic data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.
Published: 2008

11. A unique conformation of the anticodon stem-loop is associated with the capacity of tRNAfMet to initiate protein synthesis

Author: Carine Tisné, Yves Mechulam, Frédéric Dardel, Pierre Barraud, Emmanuelle Schmitt, Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biochimie de l'Ecole polytechnique ( BIOC ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), 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), Laboratoire de Biochimie de l'Ecole polytechnique (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)
Subjects: Models, Molecular, MESH : Escherichia coli, MESH : Molecular Sequence Data, MESH : Nucleic Acid Conformation, MESH: Base Sequence, Crystallography, X-Ray, chemistry.chemical_compound, MESH : Anticodon, Protein biosynthesis, MESH : RNA, Transfer, Met, Peptide Chain Initiation, Translational, 0303 health sciences, MESH: Escherichia coli, 030302 biochemistry & molecular biology, Stem-loop, RNA, Bacterial, MESH: Nucleic Acid Conformation, Biochemistry, Transfer RNA, MESH: RNA, Bacterial, MESH: Models, Molecular, MESH: Peptide Chain Initiation, Translational, RNA, Transfer, Met, MESH : Models, Molecular, Base pair, Stereochemistry, Molecular Sequence Data, Biology, 03 medical and health sciences, Eukaryotic translation, Anticodon, Escherichia coli, MESH: Anticodon, Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Molecular Sequence Data, Methionine, Base Sequence, MESH: RNA, Transfer, Met, RNA, MESH : RNA, Bacterial, MESH: Crystallography, X-Ray, chemistry, Helix, Nucleic Acid Conformation, MESH : Base Sequence, MESH : Crystallography, X-Ray, MESH : Peptide Chain Initiation, Translational
Abstract: International audience; In all organisms, translational initiation takes place on the small ribosomal subunit and two classes of methionine tRNA are present. The initiator is used exclusively for initiation of protein synthesis while the elongator is used for inserting methionine internally in the nascent polypeptide chain. The crystal structure of Escherichia coli initiator tRNA(f)(Met) has been solved at 3.1 A resolution. The anticodon region is well-defined and reveals a unique structure, which has not been described in any other tRNA. It encompasses a Cm32*A38 base pair with a peculiar geometry extending the anticodon helix, a base triple between A37 and the G29-C41 pair in the major groove of the anticodon stem and a modified stacking organization of the anticodon loop. This conformation is associated with the three GC basepairs in the anticodon stem, characteristic of initiator tRNAs and suggests a mechanism by which the translation initiation machinery could discriminate the initiator tRNA from all other tRNAs.
Published: 2008

12. Genetic diversity of Echinococcus multilocularis on a local scale

Author: Jenny Knapp, Bruno Gottstein, Patrick Giraudoux, M-H Guislain, Francis Raoul, Jean-Mathieu Bart, Renaud Piarroux, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institute of Parasitology, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: MESH : Molecular Sequence Data, Range (biology), Foxes, MESH: Base Sequence, MESH : Echinococcus multilocularis, MESH : Microsatellite Repeats, MESH: Variation (Genetics), 0302 clinical medicine, MESH : Genes, Helminth, Parasite hosting, MESH: Animals, MESH : Female, 610 Medicine & health, MESH: Phylogeny, Genes, Helminth, Phylogeny, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, 630 Agriculture, MESH : Variation (Genetics), Ecology, Infectious Diseases, Microsatellite, Female, France, Microbiology (medical), Molecular Sequence Data, 030231 tropical medicine, Zoology, Biology, Echinococcus multilocularis, MESH: Sequence Homology, Nucleic Acid, Microbiology, [ SDV.EE ] Life Sciences [q-bio]/Ecology, environment, 03 medical and health sciences, Phylogenetics, Sequence Homology, Nucleic Acid, parasitic diseases, Genetic variation, Genetics, Animals, Helminths, MESH : Sequence Homology, Nucleic Acid, MESH : France, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH: Echinococcus multilocularis, MESH : Foxes, Genetic diversity, MESH: Foxes, MESH: Molecular Sequence Data, Base Sequence, Genetic Variation, MESH : Phylogeny, biology.organism_classification, MESH: France, MESH : Base Sequence, MESH: Microsatellite Repeats, MESH : Animals, MESH: Female, Microsatellite Repeats, MESH: Genes, Helminth
Abstract: International audience; Echinococcus multilocularis is the causative agent of human Alveolar Echinococcosis (AE), and it is one of the most lethal zoonotic infections in the Northern Hemisphere. In France, the eastern and central regions are endemic areas; Franche-Comt?Lorraine and Auvergne are particularly contaminated. Recently, several human cases were recorded in the French Ardennes area, a region adjacent to the western border of the E. multilocularis range in France. A previous study in this focus described a prevalence of over 50% of the parasite in red foxes. The present study investigated the genetic diversity of adult worms collected from foxes in a 900km(2) area in the Ardennes. Instead of a conventional mitochondrial target (ATP6), two microsatellite targets (EmsB and NAK1) were used. A total of 140 adult worms isolated from 25 red foxes were genotyped. After hierarchical clustering analyses, the EmsB target enabled us to distinguish two main assemblages, each divided into sub-groups, yielding the differentiation of six clusters or assemblage profiles. Thirteen foxes (52% of the foxes) each harbored worms from at least two different assemblage profiles, suggesting they had become infected by several sources. Using the NAK1 target, we identified 3 alleles, two found in association with the two EmsB assemblages. With the NAK1 target, we investigated the parasite breeding system and the possible causes of genetic diversification. Only one fox harbored hybrid worms, indicative of a possible (and rare) occurrence of recombination, although multiple infections have been observed in foxes. These results confirm the usefulness of microsatellite targets for assessing genetic polymorphism in a geographically restricted local range.
Published: 2008

13. Hypoxia Down-regulates CCAAT/Enhancer Binding Protein-α Expression in Breast Cancer Cells

Author: Robert Barouki, Etienne Blanc, Nathalie M. Mazure, Fabrice Lecuru, Marie-Claude Fulchignoni-Lataud, Marie-Aude Le Frere Belda, Anne Dreiem, Thérèse Hervèe Mayi, Charbel Massaad, Vincent Favaudon, Liliane Massaad-Massade, Ramzi Seifeddine, Laboratoire de Détection et de Géophysique (CEA) (LDG), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), IFR50, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Génotoxicologie, signalisation et radiothérapie expérimentale, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique moléculaire, Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Stéroïdes et système nerveux : physiopathologie moléculaire et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Paris-Sud, Université Paris-Sud - Paris 11 (UP11), Toxicologie Moleculaire (U490), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Côte d'Azur (UCA), Laboratoire de Détection et de Géophysique (CEA) ( LDG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Régulation de la transcription et maladies génétiques ( RTMG ), Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Toxicologie Moleculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Faculté de Médecine Nice, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie
Subjects: Cancer Research, Hypoxia-Inducible Factor 1, MESH : Molecular Sequence Data, MESH : RNA, Messenger, Transcription, Genetic, MESH : Immunohistochemistry, MESH: Cell Hypoxia, Electrophoretic Mobility Shift Assay, MESH: Cell Cycle, RNA polymerase II, MESH : Blotting, Western, MESH : Breast Neoplasms, MESH: Base Sequence, MESH : RNA, Small Interfering, MESH: Down-Regulation, MESH : Down-Regulation, 0302 clinical medicine, Transcription (biology), MESH: Reverse Transcriptase Polymerase Chain Reaction, Enhancer binding, MESH: RNA, Small Interfering, Gene expression, MESH: CCAAT-Enhancer-Binding Protein-alpha, MESH : CCAAT-Enhancer-Binding Protein-alpha, RNA, Small Interfering, Promoter Regions, Genetic, 0303 health sciences, Gene knockdown, Reverse Transcriptase Polymerase Chain Reaction, Cell Cycle, MESH : Reverse Transcriptase Polymerase Chain Reaction, Immunohistochemistry, Cell Hypoxia, 3. Good health, MESH: Promoter Regions (Genetics), Oncology, MESH : Electrophoretic Mobility Shift Assay, 030220 oncology & carcinogenesis, MESH: Cell Growth Processes, MESH : Cell Hypoxia, MESH : Transfection, Subcellular Fractions, medicine.medical_specialty, MESH : Hypoxia-Inducible Factor 1, alpha Subunit, MESH: Cell Line, Tumor, Blotting, Western, Molecular Sequence Data, MESH : Deferoxamine, Down-Regulation, Breast Neoplasms, Cell Growth Processes, MESH : Subcellular Fractions, Deferoxamine, Biology, Transfection, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, 03 medical and health sciences, Cell Line, Tumor, Internal medicine, MESH : Cell Cycle, CCAAT-Enhancer-Binding Protein-alpha, medicine, Humans, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH: Transfection, MESH : Humans, MESH : Transcription, Genetic, MESH: Immunohistochemistry, MESH: Deferoxamine, Hypoxia-Inducible Factor 1, alpha Subunit, MESH : Promoter Regions (Genetics), Molecular biology, Endocrinology, HIF1A, MESH : Cell Growth Processes, MESH: Subcellular Fractions, MESH: Electrophoretic Mobility Shift Assay, biology.protein, MESH : Base Sequence, MESH: Breast Neoplasms
Abstract: International audience; The transcription factor CCAAT/enhancer binding protein-alpha (C/EBP alpha) is involved in the control of cell differentiation and proliferation, and has been suggested to act as a tumor suppressor in several cancers. By using microarray analysis, we have previously shown that hypoxia and estrogen down-regulate C/EBP alpha mRNA in T-47D breast cancer cells. Here, we have examined the mechanism by which the down-regulation by hypoxia takes place. Using the specific RNA polymerase II inhibitor 5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside, the mRNA stability was analyzed under normoxia or hypoxia by quantitative reverse transcription-PCR. Hypoxia reduced the half-life of C/EBP alpha mRNA by approximately 30%. C/EBP alpha gene promoter studies indicated that hypoxia also repressed the transcription of the gene and identified a hypoxia-responsive element (-522; -527 bp), which binds to hypoxia-inducible factor (HIF)-1 alpha, as essential for down-regulation of C/EBP alpha transcription in hypoxia. Immunocytochemical analysis showed that C/EBP alpha was localized in the nucleus at 21% O(2), but was mostly cytoplasmic under 1% O(2). Knockdown of HIF-1 alpha by RNAi restored C/EBP alpha to normal levels under hypoxic conditions. Immunohistochemical studies of 10 tumor samples did not show any colocalization of C/EBP alpha and glucose transporter 1 (used as a marker for hypoxia). Taken together, these results show that hypoxia down-regulates C/EBP alpha expression in breast cancer cells by several mechanisms, including transcriptional and posttranscriptional effects. The down-regulation of C/EBP alpha in hypoxia is mediated by HIF-1.
Published: 2008

14. Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria

Author: Marthe Vilotte, Patrick Calvas, Arnold Munnich, Nicolas Chassaing, Olivier Roche, Akihiko Tawara, Josseline Kaplan, Antoine Guilloux, Alain Regnier, Jean-Yves Douet, Arturo Ramirez-Miranda, Christine Bole-Feysot, Elfride De Baere, Hannah Verdin, Bruno Passet, Yusuke Nakamura, Juan Carlos Zenteno, Hiroyuki Kondo, Masaru Iwai, Ken Yamamoto, Toshihiro Tanaka, Sylvie Gerber, Jean-Michel Rozet, Jean-Luc Vilotte, Wataru Kimura, Lucas Fares-Taie, Isabelle Raymond-Letron, Hugo Moisset, Sylvie Odent, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Occupational and Environmental Health [Kitakyushu] (UEOH), Instituto de Oftalmologia Fundacion Conde de la Valenciana AC, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Center for Medical Genetics [Ghent], Ghent University Hospital, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Kyushu University [Fukuoka], Ehime University [Matsuyama], Ehime University Graduate School of Medecine, Ehime Medical Center, Tokyo Medical and Dental University, Center for Integrative Medical Sciences (RIKEN), University of Chicago, Kimura Eye Clinic, Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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) (APHP)-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 Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse, CHU Necker - Enfants Malades [AP-HP], This work was supported by grants from the Fédération des Aveugles de France (FAF) to LFT, Retina France to JMR and Geniris to JMR and PC, the Ministry of Education, Culture, Sport, Science and Technology of Japan Grant-in-aid N°20592067 to AT and the Conde de Valenciana Foundation patronage to ARM and JCZ., Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), University of Occupational and Environmental Health [Kitakyushu] ( UEOH ), Ecole Nationale Vétérinaire de Toulouse ( ENVT ), Institut National Polytechnique de Toulouse ( INPT ), Génétique Animale et Biologie Intégrative ( GABI ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Center for Integrative Medical Sciences ( RIKEN ), Structure Fédérative de Recherche Necker ( SFR Necker - UMS 3633 / US24 ), Assistance publique - Hôpitaux de Paris (AP-HP)-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)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT), Kyushu University, Ehime University [Matsuyama, Japon], Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidad Nacional Autónoma de México (UNAM), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Kagoshima University Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University [Japan] (TMDU), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), The University of Chicago Medicine [Chicago], Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), 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), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Paris Descartes - Paris 5 (UPD5), Federation des Aveugles de France (FAF), Retina France, Geniris, Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) 20592067, Conde de Valenciana Foundation patronage, Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (KAKENHI) 15K05577 221S0002, CARBILLET, Véronique, and Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)
Subjects: MESH: Sequence Analysis, DNA, [SDV]Life Sciences [q-bio], MESH : Base Sequence, Chromosome Deletion, Chromosomes, Human, Pair 13/genetics, Comparative Genomic Hybridization, Gene Components, Genes, Dominant/genetics, Humans, Hydro-Lyases/genetics, Molecular Sequence Data, Mutation/genetics, Oligonucleotide Array Sequence Analysis, Pedigree, Pupil Disorders/congenital, Pupil Disorders/genetics, Pupil Disorders/pathology, Receptors, Cell Surface/genetics, Sequence Analysis, DNA, MESH: Receptors, Cell Surface / genetics, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Receptors, G-Protein-Coupled, MESH: Base Sequence, medicine.disease_cause, MESH: Pupil Disorders / pathology, Receptors, G-Protein-Coupled, 0302 clinical medicine, MESH: Genes, Dominant / genetics, Pupil Disorders, Myocyte, Genetics(clinical), MESH: Gene Components, 10. No inequality, MESH: Hydro-Lyases / genetics, MESH: Pupil Disorders / congenital, Genetics (clinical), Genes, Dominant, Genetics, 0303 health sciences, Mutation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microcoria, MESH: Pupil Disorders / genetics, MESH: Pedigree, Receptors, Cell Surface, Biology, 03 medical and health sciences, Dysgenesis, MESH: Chromosome Deletion, Report, medicine, Gene, Hydro-Lyases, 030304 developmental biology, Sequence (medicine), [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Chromosomes, Human, Pair 13, [ SDV ] Life Sciences [q-bio], MESH: Mutation / genetics, Breakpoint, Sequence Analysis, DNA, MESH: Chromosomes, Human, Pair 13 / genetics, Molecular biology, MESH: Comparative Genomic Hybridization, MESH: Oligonucleotide Array Sequence Analysis, 030221 ophthalmology & optometry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Comparative genomic hybridization
Abstract: International audience; Congenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR.
Published: 2015

15. Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR

Author: Marc Monot, Johann Peltier, Martine Pestel-Caron, Jean-Louis Pons, Olga Soutourina, Imane El Meouche, Bruno Dupuy, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Cellule Pasteur, PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Ecosystème intestinal, probiotiques, antibiotiques (EA 4065), Université Paris Descartes - Paris 5 (UPD5), Funding was provided by the University of Rouen., Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes ( GRAM 1.0 ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Pathogénèse des Bactéries Anaérobies, Institut Pasteur [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Ecosystème intestinal, probiotiques, antibiotiques ( EA 4065 ), and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: MESH : Protein Biosynthesis, Transcription, Genetic, Mutant, lcsh:Medicine, MESH : Transcriptome, MESH : Promoter Regions, Genetic, MESH: Base Sequence, Transcription (biology), Sigma factor, Gene expression, MESH : Bacterial Proteins, MESH: Gene Silencing, lcsh:Science, Promoter Regions, Genetic, MESH : Clostridium difficile, MESH: Bacterial Proteins, MESH : Consensus Sequence, Regulation of gene expression, Genetics, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, MESH: Genetic Complementation Test, Multidisciplinary, MESH : Protein Binding, DNA-Directed RNA Polymerases, MESH : Phenotype, Phenotype, Flagella, MESH: Protein Biosynthesis, MESH: Transcription Initiation Site, Transcription Initiation Site, MESH : Mutation, Research Article, Protein Binding, MESH : Gene Expression Regulation, Bacterial, MESH: Mutation, Bacterial Toxins, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, MESH: Phenotype, MESH: Flagella, 03 medical and health sciences, Bacterial Proteins, MESH : DNA-Directed RNA Polymerases, Consensus Sequence, MESH : Gene Silencing, MESH: Promoter Regions, Genetic, Consensus sequence, Position-Specific Scoring Matrices, MESH: Protein Binding, Gene Silencing, MESH: Consensus Sequence, Gene, MESH: Clostridium difficile, 030304 developmental biology, Binding Sites, Base Sequence, MESH : Genetic Complementation Test, Clostridioides difficile, 030306 microbiology, MESH: Transcription, Genetic, MESH: Transcriptome, lcsh:R, Genetic Complementation Test, MESH : Transcription, Genetic, MESH: Position-Specific Scoring Matrices, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, MESH : Position-Specific Scoring Matrices, MESH: DNA-Directed RNA Polymerases, Regulon, MESH: Bacterial Toxins, MESH: Binding Sites, MESH : Transcription Initiation Site, Protein Biosynthesis, Mutation, MESH : Bacterial Toxins, lcsh:Q, MESH : Base Sequence, Transcriptome, MESH : Flagella, MESH : Binding Sites
Abstract: International audience; Clostridium difficile intestinal disease is mediated largely by the actions of toxins A (TcdA) and B (TcdB), whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, and vegetative autolysins. A homolog of SigD encoding gene is present in the C.difficile 630 genome. We constructed a sigD mutant in C. difficile 630 ∆erm to analyze the regulon of SigD using a global transcriptomic approach. A total of 103 genes were differentially expressed between the wild-type and the sigD mutant, including genes involved in motility, metabolism and regulation. In addition, the sigD mutant displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Genomic analysis and RACE-PCR experiments allowed us to characterize promoter sequences of direct target genes of SigD including tcdR and to identify the SigD consensus. We then established that SigD positively regulates toxin expression via direct control of tcdR transcription. Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited the positive regulation of motility and toxin synthesis by SigD. Thus, SigD appears to be the first positive regulator of the toxin synthesis in C. difficile.
Published: 2013

16. VEB-1 in Achromobacter xylosoxidans from Cystic Fibrosis Patient, France

Author: Eliane Siebor, Carine Freby, André Pechinot, Frédéric Huet, Agathe Ogier-Desserrey, Anne Houzel, Stéphanie Perez-Martin, Jean-Marie Duez, Catherine Neuwirth, UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), Laboratoire de Microbiologie Médicale et Moléculaire, Laboratoire de Bactériologie (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Humbert, Murielle, Université de Bourgogne (UB), Laboratoire de bactériologie (CHU Dijon), Plateau technique de Biologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Male, MESH : Molecular Sequence Data, integron, MESH: beta-Lactamases, lcsh:Medicine, MESH: Base Sequence, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Integron, Cystic fibrosis, Integrons, cystic fibrosis, ComputingMilieux_MISCELLANEOUS, MESH: Microbial Sensitivity Tests, 0303 health sciences, education.field_of_study, biology, Escherichia coli Proteins, MESH : beta-Lactamases, Achromobacter denitrificans, dispatch, Achromobacter xylosoxidans, MESH: Integrons, 3. Good health, MESH : Achromobacter denitrificans, France, medicine.symptom, MESH : Integrons, MESH: Cystic Fibrosis, Adolescent, MESH : Male, Molecular Sequence Data, Population, Microbial Sensitivity Tests, beta-Lactamases, Microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, MESH : Adolescent, MESH : Cystic Fibrosis, medicine, Humans, Base sequence, lcsh:RC109-216, education, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, 030306 microbiology, business.industry, MESH : Humans, lcsh:R, Extended-spectrum beta-lactamase VEB-1, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Achromobacter denitrificans, biology.protein, Sputum, MESH : Base Sequence, MESH : Microbial Sensitivity Tests, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business
Abstract: Multidrug-resistant Achromobacter xylosoxidans was recovered from the sputum of a patient with cystic fibrosis. The VEB-1 extended-spectrum β-lactamase was detected on a class 1 integron. This first report of a VEB-1–producing isolate in this population requires further investigation to determine its distribution.
Published: 2006

17. Delta-like 4 inhibits choroidal neovascularization despite opposing effects on vascular endothelium and macrophages. : DLL4's opposing effects in choroidal neovascularization

Author: Camelo, Serge, Raoul, William, Lavalette, Sophie, Calippe, Bertrand, Cristofaro, Brunella, Levy, Olivier, Houssier, Marianne, Sulpice, Eric, Jonet, Laurent, Klein, Christophe, Devevre, Estelle, Thuret, Gilles, Duarte, Antonio, Eichmann, Anne, Leconte, Laurence, Guillonneau, Xavier, Sennlaub, Florian, 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 ), Institut de la Vision, 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 interdisciplinaire de recherche en biologie ( CIRB ), Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie à Grande Échelle ( BGE - UMR S1038 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes [Saint Martin d'Hères]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Faculté de Médecine, CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Assistance Publique des Hôpitaux de St Etienne, Instituto Gulbenkian de Ciência [Oeiras] ( IGC ), Fundação Calouste Gulbenkian, Faculdade de Medicina Veterinária ( CIISA ), Universidade Técnica de Lisboa, Centre de Recherche Cardiovasculaire de Lariboisiere, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'Ophtalmologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, ANR blanc AO5120DD ANR Genopat R09099DS ERC-2007 Starting Grant 210345, 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), 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 interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Assistance Publique des Hôpitaux de St Etienne, Instituto Gulbenkian de Ciência [Oeiras] (IGC), Faculdade de Medicina Veterinária (CIISA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-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)-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), Faculté de Médecine Jacques Lisfranc [Université Saint-Etienne], and Université Jean Monnet - Saint-Étienne (UJM)
Subjects: MESH: DNA Primers, Notch, genetic structures, age related macular degeneration, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH : Blotting, Western, MESH : Mice, Inbred C57BL, MESH: Base Sequence, DLL4, MESH: Mice, Inbred C57BL, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Mice, MESH: Blotting, Western, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH: Intercellular Signaling Peptides and Proteins, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Intercellular Signaling Peptides and Proteins, MESH : Choroidal Neovascularization, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Choroidal Neovascularization, MESH : Reverse Transcriptase Polymerase Chain Reaction, eye, eye diseases, macrophages, MESH : Endothelium, Vascular, MESH : Macrophages, Peritoneal, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, MESH : Base Sequence, MESH : DNA Primers, MESH: Endothelium, Vascular, sense organs, Angiogenesis, MESH : Animals, MESH: Macrophages, Peritoneal
Abstract: International audience; Inflammatory neovascularization, such as choroidal neovascularization (CNV), occur in the presence of Notch expressing macrophages. DLL4s anti-angiogenic effect on endothelial cells (EC) has been widely recognized, but its influence on Notch signaling on macrophages and its overall effect in inflammatory neovascularization is not well understood. We identified macrophages and ECs as the main Notch 1 and Notch 4 expressing cells in CNV. A soluble fraction spanning Ser28-Pro525 of the murine extracellular DLL4 domain (sDLL4/28-525) activated the Notch pathway, as it induces Notch target genes in macrophages and ECs and inhibited EC proliferation and vascular sprouting in aortic rings. In contrast, sDLL4/28-525 increased pro-angiogenic VEGF, and IL-1β expression in macrophages responsible for increased vascular sprouting observed in aortic rings incubated in conditioned media from sDLL4/28-525 stimulated macrophages. In vivo, Dll4(+/-) mice developed significantly more CNV and sDLL4/28-525 injections inhibited CNV in Dll4(+/-) CD1 mice. Similarly, sDLL4/28-525 inhibited CNV in C57Bl6 and its effect was reversed by a γ-secretase inhibitor that blocks Notch signaling. The inhibition occurred despite increased VEGF, IL-1β expression in infiltrating inflammatory macrophages in sDLL4/28-525 treated mice and might be due to direct inhibition of EC proliferation in laser-induced CNV as demonstrated by EdU labelling in vivo. In conclusion, Notch activation on macrophages and ECs leads to opposing effects in inflammatory neovascularization in situations such as CNV.
Published: 2012

18. The nucleoid-associated protein Fis directly modulates the synthesis of cellulose, an essential component of pellicle-biofilms in the phytopathogenic bacterium Dickeya dadantii

Author: Claire Prigent-Combaret, Ouafa Zghidi-Abouzid, Géraldine Effantin, Philippe Lejeune, Sylvie Reverchon, William Nasser, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Trafic et signalisation membranaires chez les bactéries (MTSB), Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Chromatine et Régulation de la Pathogénie bactérienne (CRP), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Microbiologie, adaptation et pathogénie ( MAP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Operator Regions, Genetic, Operator Regions, Genetic, MESH : Molecular Sequence Data, MESH : Operon, MESH : Solanum tuberosum, MESH: Base Sequence, MESH: Virulence, Chicory, MESH: Plant Diseases, Genes, Reporter, [ SDV.EE.IEO ] Life Sciences [q-bio]/Ecology, environment/Symbiosis, MESH: Cellulose, MESH: Gene Expression Regulation, Bacterial, Virulence, MESH : Plant Diseases, MESH : Virulence, MESH : beta-Galactosidase, MESH : Enterobacteriaceae, MESH : Genes, Reporter, MESH: beta-Galactosidase, MESH : Biofilms, MESH: Repressor Proteins, MESH: Transcription Initiation Site, Transcription Initiation Site, MESH : Repressor Proteins, MESH : Gene Expression Regulation, Bacterial, MESH: Operon, Molecular Sequence Data, MESH: Biofilms, MESH: Solanum tuberosum, MESH: Artificial Gene Fusion, MESH: Enterobacteriaceae, Enterobacteriaceae, Operon, Cellulose, Plant Diseases, Solanum tuberosum, MESH: Molecular Sequence Data, Base Sequence, MESH : Cellulose, MESH: Genes, Reporter, Gene Expression Regulation, Bacterial, beta-Galactosidase, Artificial Gene Fusion, MESH : Chicory, Repressor Proteins, MESH : Artificial Gene Fusion, MESH : Transcription Initiation Site, MESH: Operator Regions, Genetic, Biofilms, MESH: Chicory, MESH : Base Sequence, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: International audience; Bacteria use biofilm structures to colonize surfaces and to survive in hostile conditions, and numerous bacteria produce cellulose as a biofilm matrix polymer. Hence, expression of the bcs operon, responsible for cellulose biosynthesis, must be finely regulated in order to allow bacteria to adopt the proper surface-associated behaviours. Here we show that in the phytopathogenic bacterium, Dickeya dadantii, production of cellulose is required for pellicle-biofilm formation and resistance to chlorine treatments. Expression of the bcs operon is growth phase-regulated and is stimulated in biofilms. Furthermore, we unexpectedly found that the nucleoid-associated protein and global regulator of virulence functions, Fis, directly represses bcs operon expression by interacting with an operator that is absent from the bcs operon of animal pathogenic bacteria and the plant pathogenic bacterium Pectobacterium. Moreover, production of cellulose enhances plant surface colonization by D. dadantii. Overall, these data suggest that cellulose production and biofilm formation may be important factors for surface colonization by D. dadantii and its subsequent survival in hostile environments. This report also presents a new example of how bacteria can modulate the action of a global regulator to co-ordinate basic metabolism, virulence and modifications of lifestyle.
Published: 2012

19. GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation

Author: Sylvie Salenave, Jessica Zucman-Rossi, Emmanuelle Jeannot, Gabrielle Couchy, Philippe Chanson, Paulette Bioulac-Sage, Jean-Charles Nault, Charles Balabaud, Marie-José Redon, Camilla Pilati, Sophie Prevot, Marie-Christine Saint-Paul, Philippe Labrune, Jeanne Tran Van Nhieu, Anne de Muret, Monique Fabre, Jean-Yves Scoazec, Catherine Buffet, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex Immuno-oncology, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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)-PRES Sorbonne Paris Cité-Faculté de Médecine, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Digestif, Hôpital Archet 2 [Nice] (CHU), Service d'hépato-gastro-entérologie, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Antoine-Béclère, Centre de Référence Maladies Héréditaires du Métabolisme Hépatique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie [Béclère], 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)-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)-Anipath, UFR Médecine Lyon-RTH Laennec-UFR Médecine Lyon-RTH Laennec, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service d'Endocrinologie et Maladies de la reproduction, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-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)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-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)-PRES Sorbonne Paris Cité-Faculté de Médecine, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine-Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, 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)-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)-Anipath, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Genomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Hôpital Archet 2 [Nice] ( CHU ), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine-Béclère, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Centre de Recherche en Cancérologie de Lyon ( CRCL ), 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 National de la Recherche Scientifique ( CNRS ) -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 National de la Recherche Scientifique ( CNRS ) -Anipath, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre
Subjects: Male, MESH: Signal Transduction, MESH : Liver Neoplasms, MESH : GTP-Binding Protein alpha Subunits, Gs, DNA Mutational Analysis, MESH : Aged, MESH : Models, Biological, Gene mutation, MESH: Base Sequence, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Adenoma, Liver Cell, 0302 clinical medicine, MESH: Liver Neoplasms, MESH : STAT3 Transcription Factor, GTP-Binding Protein alpha Subunits, Gs, MESH : Female, MESH: DNA Mutational Analysis, MESH: Carcinoma, Hepatocellular, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Liver Neoplasms, MESH: STAT3 Transcription Factor, DNA, Neoplasm, MESH : Adult, Middle Aged, 3. Good health, HNF1A, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, MESH : DNA, Neoplasm, MESH : Mutation, Signal Transduction, MESH : Carcinoma, Hepatocellular, Adult, STAT3 Transcription Factor, musculoskeletal diseases, Carcinoma, Hepatocellular, MESH: Mutation, MESH: Fibrous Dysplasia, Polyostotic, MESH : Male, MESH : Fibrous Dysplasia, Polyostotic, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : DNA Mutational Analysis, Biology, Fibrous Dysplasia, Polyostotic, Models, Biological, Adenoma, Liver Cell, 03 medical and health sciences, MESH : Adenoma, Liver Cell, Chromogranins, medicine, GNAS complex locus, Humans, MESH : Middle Aged, Aged, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, Base Sequence, Hepatology, Oncogene, MESH : Humans, MESH: Models, Biological, MESH: Adult, Hepatocellular adenoma, MESH: GTP-Binding Protein alpha Subunits, Gs, medicine.disease, MESH: Male, Mutation, Inflammatory Hepatocellular Adenoma, biology.protein, Cancer research, MESH : Base Sequence, Carcinogenesis, MESH: Female
Abstract: Background & Aims Mosaic G-protein alpha-subunit ( GNAS )-activating mutations are responsible for the McCune–Albright (MCA) syndrome. This oncogene that activates the adenylate cyclase is also mutated in various tumor types leading to the accumulation of cyclic-AMP. Identification of a hepatocellular adenoma (HCA) in two MCA patients led us to search for GNAS activation in benign and malignant hepatocellular carcinogenesis. Methods GNAS mutations were screened by sequencing 164 HCA, 245 hepatocellular carcinoma (HCC), and 17 fibrolamellar carcinomas. Tumors were characterized by quantitative RT-PCR, gene mutation screening and pathological reviewing. The consequences of wild type and mutant GNAS expression were analyzed in hepatocellular cell lines. Results A somatic GNAS -activating mutation was identified in 5 benign tumors and in 2 HCC. In benign tumors, GNAS mutations were exclusive from HNF1A , CTNNB1 , and IL6ST mutations whereas one HCC demonstrated both CTNNB1 and GNAS mutations. Quantitative RT-PCR showed an activation of the IL-6 and interferon pathways in GNAS -mutated tumor tissues. Accordingly, pathological reviewing identified in GNAS -mutated tumors an inflammatory phenotype characterized by fibrosis and STAT3 activation. We further demonstrated in HCC cell lines that GNAS mutant expression induced inflammatory response and STAT3 activation. Conclusions We identified for the first time the association between two rare diseases, MCA syndrome and HCA occurrence, but also that somatic GNAS -activating mutations in sporadic benign and malignant liver tumors are characterized by an inflammatory phenotype. These results showed a cross-talk between cyclic-AMP and JAK/STAT pathways in liver tumors and they reinforce the role of STAT3 activation in liver tumorigenesis.
Published: 2012

20. Investigating Alternative RNA Splicing in Xenopus

Author: Serge Hardy, Agnès Méreau, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), and Le Corre, Morgane
Subjects: Male, Oocyte, MESH : Sequence Analysis, RNA, Embryo, Nonmammalian, MESH : RNA, Messenger, MESH : Molecular Sequence Data, Xenopus, MESH: Morpholinos, MESH : Alternative Splicing, MESH : Morpholinos, Xenopus Proteins, MESH: Base Sequence, MESH: Microinjections, Splicing, Primary transcript, Chorionic Gonadotropin, Morpholinos, Xenopus laevis, 0302 clinical medicine, MESH : Embryo, Nonmammalian, Gene expression, MESH: Sequence Analysis, RNA, MESH : Xenopus laevis, MESH: Animals, MESH : Female, Regulatory Elements, Transcriptional, MESH: Xenopus Proteins, MESH: Organ Specificity, MESH : Chorionic Gonadotropin, 0303 health sciences, biology, MESH: Alternative Splicing, MESH : Xenopus Proteins, MESH: Reproductive Control Agents, Organ Specificity, Embryo, Gene Knockdown Techniques, RNA splicing, Proteome, Reproductive Control Agents, Female, Microinjections, MESH : Male, Molecular Sequence Data, Computational biology, MESH: Oocytes, MESH : Organ Specificity, MESH: Regulatory Elements, Transcriptional, 03 medical and health sciences, MESH: Chorionic Gonadotropin, MESH: Xenopus laevis, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, MESH : Regulatory Elements, Transcriptional, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: RNA, Messenger, 030304 developmental biology, Messenger RNA, MESH: Molecular Sequence Data, Base Sequence, Sequence Analysis, RNA, Mechanism (biology), MESH : Oocytes, Alternative splicing, MESH: Embryo, Nonmammalian, biology.organism_classification, MESH: Gene Knockdown Techniques, MESH : Reproductive Control Agents, MESH: Male, MESH : Microinjections, Oocytes, RNA, MESH : Base Sequence, MESH : Gene Knockdown Techniques, MESH : Animals, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Alternative splicing, the process by which distinct mature mRNAs can be produced from a single primary transcript, is a key mechanism to increase the organism complexity. The generation of alternative splicing pattern is a means to expand the proteome diversity and also to control gene expression through the regulation of mRNA abundance. Alternative splicing is therefore particularly prevalent during development and accordingly numerous splicing events are regulated in a tissue or temporal manner. To study the roles of alternative splicing during developmental processes and decipher the molecular mechanisms that underlie temporal and spatial regulation, it is important to develop in vivo whole animal studies. In this chapter, we present the advantages of using the amphibian Xenopus as a fully in vivo model to study alternative splicing and we describe the experimental procedures that can be used with Xenopus laevis embryos and oocytes to define the cis-regulatory elements and identify the associated trans-acting factors.
Published: 2012

21. Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

Author: Im, Kate M., Kirchhoff, Tomas, Wang, Xianshu, Green, Todd, Chow, Clement Y., Vijai, Joseph, Korn, Joshua, Gaudet, Mia M., Fredericksen, Zachary, Pankratz, V. Shane, Guiducci, Candace, Crenshaw, Andrew, McGuffog, Lesley, Kartsonaki, Christiana, Morrison, Jonathan, Healey, Sue, Sinilnikova, Olga M., Mai, Phuong L., Greene, Mark H., Piedmonte, Marion, Rubinstein, Wendy S., Hogervorst, Frans B. L., Rookus, Matti A., Collee, Margriet J., Hoogerbrugge, Nicoline, van Asperen, Christi J., Meijers-Heijboer, Hanne E. J., van Roozendaal, Cees E., Caldes, Trinidad, Perez Segura, Pedro, Jakubowska, Anna, Lubinski, Jan, Huzarski, Tomasz, Blecharz, Pawel, Nevanlinna, Heli, Aittomaki, Kristiina, Lazaro, Conxi, Blanco, Ignacio, Barkardottir, Rosa B., Montagna, Marco, D'Andrea, Emma, Devilee, Peter, Olopade, Olufunmilayo I., Neuhausen, Susan L., Peissel, Bernard, Bonanni, Bernardo, Peterlongo, Paolo, Singer, Christian F., Rennert, Gad, Lejbkowicz, Flavio, Andrulis, Irene L., Glendon, Gord, Ozcelik, Hilmi, Toland, Amanda Ewart, Caligo, Maria Adelaide, Beattie, Mary S., Chan, Salina B., Domchek, Susan M., Nathanson, Katherine L., Rebbeck, Timothy R., Phelan, Catherine M., Narod, Steven A., John, Esther M., Hopper, John L., Buys, Saundra, Daly, Mary B., Southey, Melissa C., Terry, Mary Beth, Tung, Nadine, Hansen, Thomas V. O., Osorio, Ana, Benitez, Javier, Duran, Mercedes, Weitzel, Jeffrey N., Garber, Judy, Hamann, Ute, Peock, Susan, Cook, Margaret, Oliver, Clare T., Frost, Debra, Platte, Radka, Evans, D. Gareth, Eeles, Ros, Izatt, Louise, Paterson, Joan, Brewer, Carole, Hodgson, Shirley V., Morrison, Patrick J., Porteous, Mary E., Walker, Lisa, Rogers, Mark T., Side, Lucy E., Godwin, Andrew K., Schmutzler, Rita K., Wappenschmidt, Barbara, Laitman, Yael, Meindl, Alfons, Deissler, Helmut, Varon-Mateeva, Raymonda, Preisler-Adams, Sabine, Kast, Karin, Venat-Bouvet, Laurence, Stoppa-Lyonnet, Dominique, Chenevix-Trench, Georgia, Easton, Douglas F., Klein, Robert J., Daly, Mark J., Friedman, Eitan, Dean, Michael, Clark, Andrew G., Altshuler, David M., Antoniou, Antonis C., Couch, Fergus J., Offit, Kenneth, Gomez Garcia, Encarna, Blok, Marinus, Gold, Bert, center for cancer research, Cancer inflammation, Department of Environmental Medicine, New York University School of Medicine-NYU Cancer Institute, Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Genetics [Boston], Harvard Medical School [Boston] ( HMS ), Cornell University, Department of Medical Genetics, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ), Queensland Institute of Medical Research, 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 ), Centre Léon Bérard [Lyon], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Department of Clinical Genetics, Erasmus University Medical Center-Family Cancer Clinic, Human Genetics, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, International Hereditary Cancer Center, Pomeranian Medical University, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Genetic Counselling Unit, Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Department of Oncology and Surgical Sciences, University of Padua and Istituto Oncologico Veneto IOV - IRCCS, Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Cancer Genetics Network, Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital ( MSH ), Section of Genetic Oncology, University Hospital and University of Pisa, Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Women's College Research Institute, University of Toronto, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Institute of Biology and Molecular Genetics, Universidad de Valladolid [Valladolid] ( UVa ), Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum ( DKFZ ), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Addenbrookes Hospital, Royal Devon & Exeter Hospital, Medical Genetics Unit, University College of London [London] ( UCL ), South East of Scotland Regional Genetics Service, Western General Hospital, Oxford Regional Genetics Service, Churchill Hospital Oxford Centre for Haematology, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Technical University of Munich ( TUM ), University Hospital Ulm, Charite berlin, Westfälische Wilhelms-Universität Münster ( WWU ), University Hospital Carl Gustav Carus, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de Génétique Oncologique, INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Molecular Biology and Genetics, Cornell University, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Harvard Medical School [Boston] (HMS), Cornell University [New York], University of Cambridge [UK] (CAM), 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), National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Universita degli Studi di Padova, Mount Sinai Hospital [Toronto, Canada] (MSH), Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Universidad de Valladolid [Valladolid] (UVa), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University College of London [London] (UCL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Universitätsklinikum Ulm - University Hospital of Ulm, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Westfälische Wilhelms-Universität Münster (WWU), Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Klinische Genetica, Universitat de Barcelona, Internal Medicine, Pediatric Surgery, 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), Mount Sinai Hospital (MSH), Technical University of Munich (TUM), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Human genetics, and CCA - Oncogenesis
Subjects: Linkage disequilibrium, endocrine system diseases, MESH : BRCA2 Protein, MESH : Genotype, Deafness, MESH: Base Sequence, MESH: Founder Effect, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, 0302 clinical medicine, MESH: BRCA2 Protein, MESH : Polychondritis, Relapsing, MESH : Female, Polychondritis, Relapsing, skin and connective tissue diseases, Genetics (clinical), Sequence Deletion, MESH: Heterozygote, Genetics, 0303 health sciences, education.field_of_study, BRCA1 Protein, Tay-Sachs disease, MESH: Sequence Deletion, Founder Effect, Ashkenazi jews, 3. Good health, MESH : Jews, MESH : Computer Simulation, 030220 oncology & carcinogenesis, MESH: Jews, Female, MESH: Polychondritis, Relapsing, Heterozygote, MESH : Heterozygote, MESH : Deafness, Genotype, Hereditary cancer and cancer-related syndromes Genetics and epigenetic pathways of disease [ONCOL 1], Population, MESH : Founder Effect, MESH: Deafness, MESH: Arthritis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Article, Chromosomes, 03 medical and health sciences, SDG 3 - Good Health and Well-being, MESH: Computer Simulation, medicine, Humans, Computer Simulation, MESH : BRCA1 Protein, education, Allele frequency, MESH : Haplotypes, 030304 developmental biology, MESH: BRCA1 Protein, BRCA2 Protein, MESH: Humans, Hereditary cancer and cancer-related syndromes [ONCOL 1], Base Sequence, Arthritis, MESH : Sequence Deletion, Haplotype, MESH : Humans, MESH: Haplotypes, MESH : Arthritis, medicine.disease, Cromosomes, Haplotypes, Jews, MESH : Base Sequence, Selective sweep, MESH: Female, Founder effect
Abstract: Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage disequilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1 Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4 Mb haplotype. Simulations based on the best inference of Ashkenazi population demography indicate that long-range haplotypes are expected in the context of a genome-wide survey. Our results are consistent with the hypothesis that a local bottleneck effect from population size constriction events could by chance have resulted in the large haplotype blocks observed at high frequency in the BRCA1 and BRCA2 regions of Ashkenazi Jews.
Published: 2011

22. The Sm-like RNA chaperone Hfq mediates transcription antitermination at Rho-dependent terminators

Author: Rabhi, Makhlouf, Espéli, Olivier, Schwartz, Annie, Cayrol, Bastien, Rahmouni, a Rachid, Arluison, Véronique, Boudvillain, Marc, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire Bioénergétique Membranaire et Stress (LBMS), Département Biochimie, Biophysique et Biologie Structurale (B3S), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Bioénergétique, Métalloprotéines et Stress ( LBMS ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Escherichia coli, MESH : Molecular Sequence Data, Transcription, Genetic, MESH : Transcription Factors, MESH: Peptide Elongation Factors, Molecular Sequence Data, Electrophoretic Mobility Shift Assay, MESH: Terminator Regions, Genetic, MESH: Escherichia coli Proteins, MESH: Host Factor 1 Protein, Host Factor 1 Protein, MESH: Base Sequence, Article, Escherichia coli, MESH: Adenosine Triphosphatases, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Peptide Elongation Factors, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Adenosine Triphosphatases, Terminator Regions, Genetic, MESH: Gene Expression Regulation, Bacterial, MESH: Molecular Sequence Data, Base Sequence, MESH : Adenosine Triphosphatases, MESH : Terminator Regions, Genetic, MESH: RNA Helicases, MESH: Escherichia coli, Escherichia coli Proteins, MESH : Escherichia coli Proteins, MESH: Transcription, Genetic, MESH : Host Factor 1 Protein, MESH : Molecular Chaperones, MESH : Transcription, Genetic, Gene Expression Regulation, Bacterial, MESH: Transcription Factors, MESH : RNA, Bacterial, Peptide Elongation Factors, MESH : RNA Helicases, RNA, Bacterial, MESH : Electrophoretic Mobility Shift Assay, MESH: Electrophoretic Mobility Shift Assay, MESH : Base Sequence, MESH: Molecular Chaperones, MESH: RNA, Bacterial, RNA Helicases, Molecular Chaperones, Transcription Factors, MESH : Gene Expression Regulation, Bacterial
Abstract: International audience; In Escherichia coli, the essential motor protein Rho promotes transcription termination in a tightly controlled manner that is not fully understood. Here, we show that the general post-transcriptional regulatory protein Hfq associates with Rho to regulate Rho function. The Hfq:Rho complex can be further stabilized by RNA bridging both factors in a configuration that inhibits the ATP hydrolysis and duplex unwinding activities of Rho and that mediates transcription antitermination at Rho-dependent terminators in vitro and in vivo. Antitermination at a prototypical terminator (λtR1) requires Hfq binding to an A/U-rich transcript region directly upstream from the terminator. Antitermination is modulated by trans-acting factors (NusG or nucleic acid competitors) that affect Hfq association with Rho or RNA. These data unveil a new Hfq function and a novel transcription regulatory mechanism with potentially important implications for bacterial RNA metabolism, gene silencing, and pathogenicity.
Published: 2011

23. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

Author: Anais Grall, Céline Derbois, Matthieu Le Gallo, Ingrid Hausser, Laetitia Lagoutte, Sébastien Küry, Judith Fischer, Catherine André, Emmanuelle Bourrat, Emmanuel Bensignor, Sandrine Planchais, Franz P.W. Radner, Éric Guaguère, Francis Galibert, Rudolf Zechner, Susanne Grond, Jacques Fontaine, Robert Zimmermann, Gwang-Jin Kim, Mark Lathrop, Frédérique Degorce-Rubiales, Anne Thomas, Didier Pin, Christophe Hitte, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Clinique Vétérinaire Saint Bernard, Institute of Molecular Biosciences, Karl-Franzens-Universität Graz, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of dermatology, University clinic Heidelberg, Electron Microscopy Core Facility, Universität Heidelberg [Heidelberg], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), 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)-Université Paris-Saclay, Institute for Human Genetics, University Clinic Freiburg, Faculty for Biology, University of Freiburg [Freiburg], Laboratoire d'Anatomie Pathologique Vétérinaire du Sud-Ouest, Animal Genetics Laboratory, Antagene, Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Clinique Vétérinaire de la Boulais, Clinique vétérinaire, Clinique vétérinaire, Bruxelles, Interactions Cellules Environnement - UR (ICE), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Zentrum für Biosystemanalyse, Albert-Ludwigs-Universität Freiburg, This study was supported by CNRS, the European Commission (FP7-LUPA, GA-201370). R. Zechner and R. Zimmermann were supported by the FWF F30 SFB Lipotox, Z136 Wittgenstein, the GEN-AU project GOLD by the Austrian Ministry of Science and Research and FFG. I.H. was supported by the NIRK Network (German BMBF 01GM0904)., European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de Génomique d'Evry ( IG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Trousseau [APHP], Unité de Dermatologie, VetAgro Sup ( VAS ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, European Project : 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA ( 2008 ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Heidelberg [Heidelberg] = Heidelberg University, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), De Villemeur, Hervé, and Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID
Subjects: Male, MESH : Molecular Sequence Data, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Base Sequence, medicine.disease_cause, 0403 veterinary science, MESH: Dogs, MESH: INDEL Mutation, MESH: Lipase, MESH : Dogs, INDEL Mutation, Congenital ichthyosis, Missense mutation, MESH : Female, MESH: Animals, MESH: Codon, Nonsense, Cells, Cultured, Skin, Genetics, 0303 health sciences, Mutation, 04 agricultural and veterinary sciences, Lamellar ichthyosis, MESH : Adult, MESH : Lipase, MESH : Dermatologic Agents, MESH : Codon, Nonsense, MESH: Ichthyosis, Lamellar, Codon, Nonsense, Female, MESH : Genome-Wide Association Study, MESH: Cells, Cultured, Adult, 040301 veterinary sciences, MESH : Male, Nonsense mutation, Molecular Sequence Data, Mutation, Missense, ALOX12B, Golden Retriever, Genes, Recessive, MESH: Nitrendipine, Biology, 03 medical and health sciences, Dogs, MESH: Skin, MESH : Cells, Cultured, medicine, MESH : Skin, Animals, Humans, Indel, MESH : INDEL Mutation, MESH: Genes, Recessive, 030304 developmental biology, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Nitrendipine, MESH : Humans, MESH : Ichthyosis, Lamellar, MESH : Genes, Recessive, MESH: Adult, Lipase, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, MESH : Nitrendipine, MESH: Male, MESH: Dermatologic Agents, MESH: Genome-Wide Association Study, MESH : Base Sequence, MESH : Animals, Dermatologic Agents, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Female, MESH : Mutation, Missense, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Ichthyosis, Lamellar, Genome-Wide Association Study
Abstract: International audience; Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.
Published: 2011

24. Spectrum of mutations in Gitelman syndrome

Author: Annabelle Venisse, Diana Kahila, Claire Rigothier, Bernard Grisart, Bruno Moulin, Marie-Christine Vantyghem, Ivan Tack, Anne-Paule Gimenez-Roqueplo, Franck Bridoux, Jean-Philippe Haymann, Olivier Devuyst, Hubert Nivet, Rosa Vargas-Poussou, Laurence Dubourg, Eva Riveira-Munoz, Anne Blanchard, Karin Dahan, Michel Godin, Pascal Houillier, Huguette Debaix, Bertrand Dussol, Robert J. Unwin, Xavier Jeunemaitre, Service de néphrologie - hémodialyse et transplantation rénale, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Physiology, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Klinik für Nephrologie, UniversitätsSpital, Division of Nephrology, UCL Medical School, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), University of Zürich [Zürich] (UZH)-Zurich Center for Integrative Human Physiology, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, MESH : Molecular Sequence Data, MESH : Retrospective Studies, Receptors, Drug, Gene Dosage, 030232 urology & nephrology, MESH: Base Sequence, MESH : Child, Preschool, medicine.disease_cause, MESH: Gitelman Syndrome, MESH: Gene Dosage, MESH : Chloride Channels, 0302 clinical medicine, MESH : Child, MESH: Child, Missense mutation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Solute Carrier Family 12, Member 3, MESH : Female, MESH : Gene Dosage, Child, Gene Rearrangement, Genetics, 0303 health sciences, Mutation, MESH: Middle Aged, Symporters, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, MESH : Adult, 3. Good health, Nephrology, MESH: Young Adult, Child, Preschool, MESH : Symporters, MESH: Solute Carrier Family 12, Member 3, MESH : Gitelman Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, MESH : Sensitivity and Specificity, Gitelman Syndrome, Adult, MESH: Symporters, MESH: Mutation, Adolescent, MESH: Gene Rearrangement, MESH : Male, Molecular Sequence Data, Non-allelic homologous recombination, MESH : Young Adult, MESH : Solute Carrier Family 12, Member 3, Biology, Sensitivity and Specificity, Gene dosage, Young Adult, 03 medical and health sciences, Chloride Channels, MESH: Receptors, Drug, MESH : Adolescent, MESH : Genetic Testing, medicine, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Genetic Testing, Multiplex ligation-dependent probe amplification, Allele, Alleles, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Receptors, Drug, MESH: Alleles, MESH: Child, Preschool, MESH: Chloride Channels, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, Gene rearrangement, MESH : Gene Rearrangement, Gitelman syndrome, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, Basic Research, MESH : Genetic Predisposition to Disease, MESH : Base Sequence, MESH : Alleles, MESH: Female
Abstract: International audience; Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.
Published: 2011

25. Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam : an ANRS AC12 working group study

Author: Martine Peeters, Eric Nerrienet, Tawee Donchai, Ahidjo Ayouba, Ton Tran, Janin Nouhin, Marie-Laure Chaix, Nicole Ngo-Giang-Huong, Sreymom Ken, Truong Xuan Lien, Khanh Thu Huynh Hoang, Jiraporn Kamkorn, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University-Chiang Mai University (CMU), Institut Pasteur d'Ho Chi Minh Ville, VIH/SIDA et maladies associées, Université Montpellier 1 (UM1), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Immunology and Infectious Diseases, Harvard School of Public Health, Harvard University [Cambridge]-Chiang Mai university (Thaïlande), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est ( IRD_PHPT ), Réseau International des Instituts Pasteur ( RIIP ) -Institut Pasteur d'Ho Chi Minh Ville, Université Montpellier 1 ( UM1 ), Université Paris Descartes - Paris 5 ( UPD5 ), and Harvard University [Cambridge]-Chiang Mai University (CMU)
Subjects: MESH: CD4 Lymphocyte Count, MESH : Polymorphism, Genetic, Integrase inhibitor, HIV Infections, HIV Integrase, Drug resistance, MESH: Base Sequence, Polymerase Chain Reaction, MESH: HIV-1, 0302 clinical medicine, 030212 general & internal medicine, MESH: Anti-HIV Agents, MESH : Polymerase Chain Reaction, MESH : Algorithms, Genetics, 0303 health sciences, MESH: HIV Infections, Thailand, MESH: Amino Acid Substitution, 3. Good health, Integrase, Infectious Diseases, Vietnam, Lentivirus, MESH : DNA Primers, Cambodia, Algorithms, MESH : HIV-1, medicine.drug, MESH: DNA Primers, Microbiology (medical), Anti-HIV Agents, MESH: Algorithms, Biology, South East Asia, Microbiology, Virus, 03 medical and health sciences, MESH : Amino Acid Substitution, Resistance mutations, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, HIV-1 integrase, MESH: Polymorphism, Genetic, MESH : CD4 Lymphocyte Count, MESH : HIV Infections, Consensus sequence, medicine, Humans, MESH: Thailand, Molecular Biology, Ecology, Evolution, Behavior and Systematics, DNA Primers, 030304 developmental biology, Polymorphism, Genetic, MESH: Humans, Base Sequence, MESH : Cambodia, MESH : Anti-HIV Agents, MESH: Cambodia, MESH : Humans, MESH: Polymerase Chain Reaction, MESH : Vietnam, MESH : Thailand, biology.organism_classification, Raltegravir, Virology, CD4 Lymphocyte Count, Multiple drug resistance, Amino Acid Substitution, HIV-1, biology.protein, MESH : Base Sequence, MESH: Vietnam, MESH: HIV Integrase, Antiretroviral naive, MESH : HIV Integrase, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The HIV integrase enzyme is essential for the HIV life cycle as it mediates integration of HIV-1 proviral DNA into the infected cell's genome. Recently, the development of drugs capable of inhibiting integrase has provided major new options for HIV-infected, treatment-experienced patients with multidrug resistant virus, as well treatment-naïve patients. More than 40 amino acid substitutions within integrase have been described as associated mostly with resistance of HIV B-subtypes to currently available integrase inhibitors (INIs). We have analyzed the natural polymorphisms of the integrase coding region in 87 antiretroviral-naïve subjects (32 from Cambodia, 37 from Thailand and 18 from Vietnam) infected with CRF01_AE virus, the predominant HIV-1 strain circulating in Southeast Asia. The 864bp integrase coding region was sequenced using the ANRS consensus sequencing technique from plasma samples, and amino acid results were interpreted for drug resistance according to the ANRS (Updated July 2009, version 18) and Stanford algorithms (Version November 6, 2009). Alignment of the 87 amino acid sequences against the 2004 Los Alamos HIV-1 clade B consensus sequence showed that overall, 119 of 288 (41.3%) amino acid positions presented at least one polymorphism each. Substitutions found in >60% of study subjects occurred at: K14, A21, V31, S39, I72, T112, T124, T125, G134, I135, K136, D167, V201, L234 and S283. Also, new amino acid substitutions of as yet unknown significance were identified: E152K/H, S153F/L, N155I and E157G. None of the known integrase resistance mutations were observed, except E157Q found in one Cambodian subject (1.1%, CI 95% 0.02-6.3%). The clinical impact of this substitution on resistance of B and nonB-viruses to the licensed INI raltegravir is unclear. If this substitution is confirmed to compromise the virologic response to raltegravir, further studies will be needed to better assess the prevalence of this substitution among CRF01_AE virus.
Published: 2011

26. Neuropilin-2 expression promotes TGF-β1-mediated epithelial to mesenchymal transition in colorectal cancer cells

Author: Christophe Ferrand, Benoit Simon, Erika Viel, Christophe Borg, Wilfrid Boireau, Jean René Pallandre, Michael Klagsbrun, Adeline Bouard, Severine Valmary Degano, Jean-Paul Remy-Martin, Alain Rouleau, Jérémy Balland, Camille Grandclement, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Vascular Biology Program, Department of Surgery and Pathology, Harvard Medical School [Boston] ( HMS ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'urologie, andrologie et transplantation rénale, and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques
Subjects: Neuropilins, MESH : Receptors, Transforming Growth Factor beta, Colorectal cancer, Signal transduction, MESH: Base Sequence, MESH : RNA, Small Interfering, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Phosphorylation, 0302 clinical medicine, MESH : Cell Proliferation, Membrane Receptor Signaling, Biomacromolecule-Ligand Interactions, lcsh:Science, 0303 health sciences, Colon Adenocarcinoma, Signaling cascades, Cell biology, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, cardiovascular system, Medicine, MESH : Colorectal Neoplasms, MESH : Gene Expression Regulation, Neoplastic, MESH: Neuropilin-2, Cell Growth, 03 medical and health sciences, Gastrointestinal Tumors, Humans, MESH: Smad3 Protein, Biology, Oncogenic Signaling, MESH: Humans, Smad Signaling, MESH: Phosphorylation, MESH : Humans, lcsh:R, medicine.disease, MESH: Gene Knockdown Techniques, Neuropilin-2, MESH: Epithelial-Mesenchymal Transition, Cancer cell, MESH : Gene Knockdown Techniques, lcsh:Q, Gene expression, MESH : Transforming Growth Factor beta1, Receptors, Transforming Growth Factor beta, MESH: Signal Transduction, Angiogenesis, lcsh:Medicine, Vimentin, Smad2 Protein, MESH: Transforming Growth Factor beta1, Molecular cell biology, RNA interference, MESH: RNA, Small Interfering, MESH : Smad3 Protein, Signaling in Cellular Processes, Phosphorylation, RNA, Small Interfering, MESH: Smad2 Protein, Multidisciplinary, biology, MESH: Gene Expression Regulation, Neoplastic, Signaling in Selected Disciplines, respiratory system, MESH : Epithelial-Mesenchymal Transition, Gene Knockdown Techniques, embryonic structures, MESH: Receptors, Transforming Growth Factor beta, Colorectal Neoplasms, Research Article, Epithelial-Mesenchymal Transition, MESH: Cell Line, Tumor, animal structures, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transforming Growth Factor beta1, MESH : Smad2 Protein, Cell Line, Tumor, MESH: Cell Proliferation, medicine, Smad3 Protein, Epithelial–mesenchymal transition, Cell Proliferation, 030304 developmental biology, MESH : Signal Transduction, Base Sequence, MESH : Cell Line, Tumor, Cancers and Neoplasms, Cancer, MESH : Cell Transformation, Neoplastic, TGF-beta signaling cascade, MESH: Cell Transformation, Neoplastic, biology.protein, MESH : Base Sequence, sense organs, MESH : Neuropilin-2, MESH: Colorectal Neoplasms
Abstract: International audience; Neuropilins, initially characterized as neuronal receptors, act as co-receptors for cancer related growth factors and were recently involved in several signaling pathways leading to cytoskeletal organization, angiogenesis and cancer progression. Then, we sought to investigate the ability of neuropilin-2 to orchestrate epithelial-mesenchymal transition in colorectal cancer cells. Using specific siRNA to target neuropilin-2 expression, or gene transfer, we first observed that neuropilin-2 expression endows HT29 and Colo320 for xenograft formation. Moreover, neuropilin-2 conferred a fibroblastic-like shape to cancer cells, suggesting an involvement of neuropilin-2 in epithelial-mesenchymal transition. Indeed, the presence of neuropilin-2 in colorectal carcinoma cell lines was correlated with loss of epithelial markers such as cytokeratin-20 and E-cadherin and with acquisition of mesenchymal molecules such as vimentin. Furthermore, we showed by surface plasmon resonance experiments that neuropilin-2 is a receptor for transforming-growth factor-β1. The expression of neuropilin-2 on colon cancer cell lines was indeed shown to promote transforming-growth factor-β1 signaling, leading to a constitutive phosphorylation of the Smad2/3 complex. Treatment with specific TGFβ-type1 receptor kinase inhibitors restored E-cadherin levels and inhibited in part neuropilin-2-induced vimentin expression, suggesting that neuropilin-2 cooperates with TGFβ-type1 receptor to promote epithelial-mesenchymal transition in colorectal cancer cells. Our results suggest a direct role of NRP2 in epithelial-mesenchymal transition and highlight a cross-talk between neuropilin-2 and TGF-β1 signaling to promote cancer progression. These results suggest that neuropilin-2 fulfills all the criteria of a therapeutic target to disrupt multiple oncogenic functions in solid tumors.
Published: 2011

27. A non-covalent peptide-based strategy for siRNA delivery

Author: Crombez , Laurence, Divita , Gilles, Centre de recherches de biochimie macromoléculaire ( CRBM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR122-Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche en Biologie Cellulaire (CRBM), and Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, MESH : RNA, Messenger, MESH : Drug Carriers, Blotting, Western, Molecular Sequence Data, Cell-Penetrating Peptides, MESH: Amino Acid Sequence, MESH : Blotting, Western, MESH: Base Sequence, Transfection, MESH : RNA, Small Interfering, Cell Line, MESH: Cell Adhesion, MESH : Cell-Penetrating Peptides, MESH: RNA, Small Interfering, MESH : Gene Silencing, Cell Adhesion, Animals, Humans, MESH: Blotting, Western, MESH: Animals, MESH: Gene Silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Gene Silencing, RNA, Messenger, RNA, Small Interfering, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: RNA, Messenger, MESH: Cell-Penetrating Peptides, Drug Carriers, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH: Transfection, MESH : Amino Acid Sequence, MESH : Humans, MESH: Cell Line, MESH: Drug Carriers, MESH : Cell Adhesion, MESH : Base Sequence, MESH : Animals, MESH : Transfection
Abstract: International audience; The development of short-interfering RNA (siRNA) has provided great hope for therapeutic targeting of specific genes responsible for pathological disorders. However, the poor cellular uptake of siRNA together with the low permeability of the cell membrane to negatively charged molecules, remain major obstacles to clinical development. So far there is no universal method for siRNA delivery as they all present several limitations. Several non-viral strategies have been proposed to improve the delivery of synthetic siRNAs in both cultured cells and in vivo. Cell-penetrating peptides (CPPs) or protein transduction domains (PTD) constitute very promising tools for non-invasive cellular import of siRNA and non-covalent CPP/PTD-based strategies have been successfully applied for ex vivo and in vivo delivery of therapeutic siRNA molecules. We recently described a new peptide-based system, CADY, for efficient delivery of siRNA in both primary and suspension cell lines. CADY is a secondary amphiphatic peptide able to form stable non-covalent complexes with siRNA and to improve their cellular uptake independently of the endosomal pathway. This chapter describes easy to handle protocols for the use of the CADY-nanoparticle technology for the delivery of siRNA into both adherent and suspension cell lines. It will also highlight different critical points in the peptide/siRNA complex preparation and transfection protocols, in order to obtain siRNA-associated interfering response at low nanomolar concentration.
Published: 2011

28. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Author: Anderson Miyoshi, Vasco Azevedo, Lisa Ott, Andreas Burkovski, Flávia S. Rocha, Fernanda Alves Dorella, Olivier Join-Lambert, Eva Trost, Samer Kayal, Alexander Goesmann, Nicole Guiso, Peter Husemann, Jens Stoye, Artur Silva, Andreas Tauch, Vivian D'Afonseca, Sebastian Jaenicke, Jerónimo Saiz Ruiz, Siomar de Castro Soares, Jessica Schneider, Jasmin Schröder, Institut für Genomforschung und Systembiologie, Universität Bielefeld-Centrum für Biotechnologie, CLIB Graduate Cluster Industrial Biotechnology, Lehrstuhl für Mikrobiologie, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Bioinformatics Resource Facility, AG Genominformatik, Universität Bielefeld-Technische Fakultät, Laboratório de Genética Celular e Molecular, Instituto de Ciências Biológicas [Goiânia, Brésil] (ICB)-Universidade Federal de Minas Gerais, Cellular and Molecular Parasitology / Parasitologia Celular e Molecular [Belo Horizonte, Brésil], Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto de Ciências Biológicas, Federal University of Para - Universidade Federal do Pará - UFPA [Belém, Brazil] (UFPA), Prévention et Thérapie Moléculaires des Maladies Infectieuses Humaines, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service de Microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Médecine-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Bielefeld University and the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia. LO and AB were supported by the Deutsche Forschungsgemeinschaft in frame of SFB 796 (project B5)., BMC, Ed., Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Federal University of Para - Universidade Federal do Para [Belem - Brésil], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centrum für Biotechnologie-Universität Bielefeld, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Instituto de Ciências Biológicas [Goiânia, Brésil] ( ICB ) -Universidade Federal de Minas Gerais, Cellular and Molecular Parasitology Laboratory, Rene Rachou Research Center-Fundação Oswaldo Cruz ( FIOCRUZ ), Universidade Federal do Pará, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Faculté de Médecine-CHU Necker - Enfants Malades [AP-HP]
Subjects: MESH : Virulence Factors, MESH: Sequence Analysis, DNA, Transcription, Genetic, Corynebacterium pseudotuberculosis, MESH : Molecular Sequence Annotation, MESH: Base Sequence, MESH: Virulence, MESH: Genome, Bacterial, MESH: Zinc, MESH : Iron, Bacterial Adhesion, MESH : Child, MESH: Child, MESH : Female, Gene Regulatory Networks, Child, Pathogen, Histiocytic Necrotizing Lymphadenitis, MESH: Gene Regulatory Networks, 0303 health sciences, MESH: Iron, Virulence, MESH : Genes, Bacterial, MESH : Fimbriae, Bacterial, MESH : Virulence, Zinc, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Regulon, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, DNA microarray, MESH: Genes, Bacterial, Research Article, Biotechnology, lcsh:QH426-470, MESH : Bacterial Adhesion, Virulence Factors, Iron, lcsh:Biotechnology, MESH : Genome, Bacterial, MESH : Regulon, MESH: Manganese, MESH: Molecular Sequence Annotation, Biology, Regulon, Microbiology, MESH: Fimbriae, Bacterial, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:TP248.13-248.65, Genetics, Humans, MESH: Bacterial Adhesion, 030304 developmental biology, MESH: Virulence Factors, Whole genome sequencing, Manganese, MESH : Corynebacterium pseudotuberculosis, MESH: Humans, Base Sequence, 030306 microbiology, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Molecular Sequence Annotation, MESH : Zinc, MESH : Histiocytic Necrotizing Lymphadenitis, Sequence Analysis, DNA, MESH: Corynebacterium pseudotuberculosis, MESH: Histiocytic Necrotizing Lymphadenitis, lcsh:Genetics, Genes, Bacterial, MESH : Gene Regulatory Networks, Fimbriae, Bacterial, Pyrosequencing, Caseous lymphadenitis, MESH : Base Sequence, MESH : Manganese, MESH: Female, Genome, Bacterial, MESH : Sequence Analysis, DNA
Abstract: Background Corynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated. Results Sequencing and assembly of the C. pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of 2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with iron and zinc homeostasis were detected among the 2,110 predicted protein-coding regions and integrated into a gene-regulatory network that is linked with both the central metabolism and the oxidative stress response of FRC41. Two gene clusters encode proteins involved in the sortase-mediated polymerization of adhesive pili that can probably mediate the adherence to host tissue to facilitate additional ligand-receptor interactions and the delivery of virulence factors. The prominent virulence factors phospholipase D (Pld) and corynebacterial protease CP40 are encoded in the genome of this human isolate. The genome annotation revealed additional serine proteases, neuraminidase H, nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase subunits involved in mycolic acid biosynthesis as potential virulence factors. The cAMP-sensing transcription regulator GlxR plays a key role in controlling the expression of several genes contributing to virulence. Conclusion The functional data deduced from the genome sequencing and the extended knowledge of virulence factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped with a distinct gene set promoting its survival under unfavorable environmental conditions encountered in the mammalian host.
Published: 2010

29. Phylogenetic relationships within Echinococcus and Taenia tapeworms (Cestoda: Taeniidae): an inference from nuclear protein-coding genes

Author: Jenny Knapp, Akira Ito, Minoru Nakao, Antti Lavikainen, Tetsuya Yanagida, Urmas Saarma, Munehiro Okamoto, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Asahikawa Medical University, Primate Research Institute, Kyoto University [Kyoto], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Paraphyly, MESH: Sequence Analysis, DNA, Time Factors, MESH : Polymorphism, Genetic, MESH: Echinococcus, Helminth genetics, MESH: Base Sequence, MESH: DNA, Helminth, MESH: Genetic Markers, Polymerase Chain Reaction, 030308 mycology & parasitology, MESH : Taenia, MESH : DNA, Helminth, MESH : Genes, Helminth, MESH : Echinococcus, MESH : Genetic Markers, MESH: Animals, MESH: Phylogeny, Clade, MESH : Polymerase Chain Reaction, Genes, Helminth, Phylogeny, 0303 health sciences, Likelihood Functions, Phylogenetic tree, biology, Nuclear Proteins, DNA, Helminth, MESH: Taenia, MESH : RNA Polymerase II, RNA Polymerase II, MESH : Likelihood Functions, MESH : Time Factors, Genetic Markers, MESH: Bayes Theorem, Zoology, MESH : Open Reading Frames, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, Open Reading Frames, MESH : Bayes Theorem, Phylogenetics, MESH: Polymorphism, Genetic, parasitic diseases, Genetics, Animals, Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Polymorphism, Genetic, Base Sequence, Taenia, MESH: Time Factors, MESH : Humans, MESH : Phylogeny, MESH : Nuclear Proteins, MESH: Polymerase Chain Reaction, Bayes Theorem, Sequence Analysis, DNA, MESH: Open Reading Frames, biology.organism_classification, MESH: RNA Polymerase II, Echinococcus, Taeniidae, MESH: Likelihood Functions, MESH : Base Sequence, MESH : Animals, MESH: Nuclear Proteins, MESH: Genes, Helminth, MESH : Sequence Analysis, DNA
Abstract: International audience; The family Taeniidae of tapeworms is composed of two genera, Echinococcus and Taenia, which obligately parasitize mammals including humans. Inferring phylogeny via molecular markers is the only way to trace back their evolutionary histories. However, molecular dating approaches are lacking so far. Here we established new markers from nuclear protein-coding genes for RNA polymerase II second largest subunit (rpb2), phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold). Bayesian inference and maximum likelihood analyses of the concatenated gene sequences allowed us to reconstruct phylogenetic trees for taeniid parasites. The tree topologies clearly demonstrated that Taenia is paraphyletic and that the clade of Echinococcus oligarthrus and Echinococcusvogeli is sister to all other members of Echinococcus. Both species are endemic in Central and South America, and their definitive hosts originated from carnivores that immigrated from North America after the formation of the Panamanian land bridge about 3 million years ago (Ma). A time-calibrated phylogeny was estimated by a Bayesian relaxed-clock method based on the assumption that the most recent common ancestor of E. oligarthrus and E. vogeli existed during the late Pliocene (3.0 Ma). The results suggest that a clade of Taenia including human-pathogenic species diversified primarily in the late Miocene (11.2 Ma), whereas Echinococcus started to diversify later, in the end of the Miocene (5.8 Ma). Close genetic relationships among the members of Echinococcus imply that the genus is a young group in which speciation and global radiation occurred rapidly.
Published: 2010

30. Identification of small RNAs in Francisella tularensis

Author: Guillaume Postic, Eric Frapy, Marion Dupuis, Alain Charbit, Jonathan Livny, Iharilalao Dubail, Karin L. Meibom, Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Broad Institute of MIT and Harvard ( BROAD INSTITUTE ), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston] ( MGH ) -Massachusetts Institute of Technology ( MIT ), Channing Laboratories, Brigham and Women's Hospital [Boston], Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], and BMC, Ed.
Subjects: MESH : Molecular Sequence Data, MESH : DNA, Complementary, MESH : Nucleic Acid Conformation, Intracellular Space, MESH : Intracellular Space, MESH: Base Sequence, Genome, RNA Transport, Mice, MESH: RNA Transport, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, Cloning, Molecular, Francisella tularensis, MESH : RNA Transport, Oligonucleotide Array Sequence Analysis, MESH : Macrophages, Genetics, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, MESH : Francisella tularensis, Reverse Transcriptase Polymerase Chain Reaction, MESH : Blotting, Northern, MESH : Reverse Transcriptase Polymerase Chain Reaction, Bacterial vaccine, MESH: Reproducibility of Results, RNA, Bacterial, MESH : Oligonucleotide Array Sequence Analysis, MESH: Nucleic Acid Conformation, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Bacterial Vaccines, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Intracellular Space, DNA microarray, MESH : Mutation, MESH: RNA, Bacterial, Biotechnology, Research Article, MESH: Computational Biology, MESH : Gene Expression Regulation, Bacterial, DNA, Complementary, MESH: Mutation, lcsh:QH426-470, MESH : Cloning, Molecular, lcsh:Biotechnology, In silico, Molecular Sequence Data, Context (language use), Biology, Vaccines, Attenuated, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Francisella tularensis, lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Vaccines, Attenuated, MESH : Mice, Animals, MESH: Blotting, Northern, MESH: Cloning, Molecular, MESH : Vaccines, Attenuated, MESH: Mice, 030304 developmental biology, MESH: Molecular Sequence Data, Base Sequence, 030306 microbiology, Gene Expression Profiling, Macrophages, MESH : Reproducibility of Results, MESH : Gene Expression Profiling, RNA, Computational Biology, Reproducibility of Results, MESH: Macrophages, Gene Expression Regulation, Bacterial, MESH: DNA, Complementary, MESH : RNA, Bacterial, biology.organism_classification, Blotting, Northern, Gene expression profiling, MESH : Bacterial Vaccines, lcsh:Genetics, Mutation, MESH: Oligonucleotide Array Sequence Analysis, Nucleic Acid Conformation, MESH : Base Sequence, MESH : Animals, MESH: Bacterial Vaccines, MESH : Computational Biology
Abstract: Background Regulation of bacterial gene expression by small RNAs (sRNAs) have proved to be important for many biological processes. Francisella tularensis is a highly pathogenic Gram-negative bacterium that causes the disease tularaemia in humans and animals. Relatively little is known about the regulatory networks existing in this organism that allows it to survive in a wide array of environments and no sRNA regulators have been identified so far. Results We have used a combination of experimental assays and in silico prediction to identify sRNAs in F. tularensis strain LVS. Using a cDNA cloning and sequencing approach we have shown that F. tularensis expresses homologues of several sRNAs that are well-conserved among diverse bacteria. We have also discovered two abundant putative sRNAs that share no sequence similarity or conserved genomic context with any previously annotated regulatory transcripts. Deletion of either of these two loci led to significant changes in the expression of several mRNAs that likely include the cognate target(s) of these sRNAs. Deletion of these sRNAs did not, however, significantly alter F. tularensis growth under various stress conditions in vitro, its replication in murine cells, or its ability to induce disease in a mouse model of F. tularensis infection. We also conducted a genome-wide in silico search for intergenic loci that suggests F. tularensis encodes several other sRNAs in addition to the sRNAs found in our experimental screen. Conclusion Our findings suggest that F. tularensis encodes a significant number of non-coding regulatory RNAs, including members of well conserved families of structural and housekeeping RNAs and other poorly conserved transcripts that may have evolved more recently to help F. tularensis deal with the unique and diverse set of environments with which it must contend.
Published: 2010

31. TRPC1 is regulated by caveolin-1 and is involved in oxidized LDL-induced apoptosis of vascular smooth muscle cells

Author: Bertrand Marcheix, Cécile Vindis, Cécile Ingueneau, Anne Nègre-Salvayre, Anne Athias, Robert Salvayre, Philippe Gambert, Uyen Huynh-Do, Institut de médecine moléculaire de Rangueil ( I2MR ), Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement of Nephrology and Hypertension, and Department of Clinical research, University of Bern, Plateforme Lipidomique [Dijon] ( LAP ), 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 ) -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 ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), 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), Plateforme Lipidomique [Dijon] (LAP), 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)-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)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Simon, Marie Francoise
Subjects: MESH: Lipoproteins, LDL, Vascular smooth muscle, Oxysterol, Caveolin 1, Apoptosis, Biology, MESH: Base Sequence, MESH : RNA, Small Interfering, Muscle, Smooth, Vascular, TRPC1, Transient receptor potential channel, MESH: RNA, Small Interfering, MESH : Cells, Cultured, Humans, MESH: Caveolin 1, RNA, Small Interfering, MESH: TRPC Cation Channels, Cells, Cultured, TRPC Cation Channels, MESH: Humans, Base Sequence, MESH : Gene Expression Regulation, MESH: Apoptosis, MESH : Humans, MESH : TRPC Cation Channels, MESH : Muscle, Smooth, Vascular, Articles, Cell Biology, MESH: Muscle, Smooth, Vascular, Actin cytoskeleton, MESH: Gene Expression Regulation, Cell biology, Lipoproteins, LDL, Gene Expression Regulation, MESH : Caveolin 1, Molecular Medicine, lipids (amino acids, peptides, and proteins), MESH : Base Sequence, MESH : Lipoproteins, LDL, Homeostasis, MESH : Apoptosis, MESH: Cells, Cultured
Abstract: International audience; Oxidized low-density lipoprotein (oxLDL) induced-apoptosis of vascular cells may participate in plaque instability and rupture. We have previously shown that vascular smooth muscle cells (VSMC) stably expressing caveolin-1 were more susceptible to oxLDL-induced apoptosis than VSMC expressing lower level of caveolin-1, and this was correlated with enhanced Ca(2+) entry and pro-apoptotic events. In this study, we aimed to identify the molecular events involved in oxLDL-induced Ca(2+) influx and their regulation by the structural protein caveolin-1. In VSMC, transient receptor potential canonical-1 (TRPC1) silencing by ARN interference prevents the Ca(2+) influx and reduces the toxicity induced by oxLDL. Moreover, caveolin-1 silencing induces concomitant decrease of TRPC1 expression and reduces oxLDL-induced apoptosis of VSMC. OxLDL enhanced the cell surface expression of TRPC1, as shown by biotinylation of cell surface proteins, and induced TRPC1 translocation into caveolar compartment, as assessed by subcellular fractionation. OxLDL-induced TRPC1 translocation was dependent on actin cytoskeleton and associated with a dramatic rise of 7-ketocholesterol (a major oxysterol in oxLDL) into caveolar membranes, whereas the caveolar content of cholesterol was unchanged. Altogether, the reported results show that TRPC1 channels play a role in Ca(2+) influx and Ca(2+) homeostasis deregulation that mediate apoptosis induced by oxLDL. These data also shed new light on the role of caveolin-1 and caveolar compartment as important regulators of TRPC1 trafficking to the plasma membrane and apoptotic processes that play a major role in atherosclerosis.
Published: 2009

32. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

Author: Fabienne Meggetto, Alan Bénard, Nadine Cogne, Aurélie Chanut, Nathalie Faumont, Georges Delsol, Jean Feuillard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Physiopathologie Toulouse Purpan (CPTP), 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)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de Physiopathologie Toulouse Purpan, and Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, DNA Mutational Analysis, MESH: NF-kappa B, Apoptosis, MESH: Base Sequence, medicine.disease_cause, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Luciferases, Renilla, immune system diseases, hemic and lymphatic diseases, MESH : Hodgkin Disease, Tumor Cells, Cultured, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Viral Matrix Proteins, MESH: Genetic Variation, Reed-Sternberg Cells, MESH: DNA Mutational Analysis, MESH : Immunoblotting, MESH: Reed-Sternberg Cells, Oncogene Proteins, Genetics, B-Lymphocytes, 0303 health sciences, Mutation, MESH: Immunoblotting, MESH : Oncogene Proteins, NF-kappa B, Hematology, Transfection, Hodgkin Disease, MESH: Hodgkin Disease, MESH : NF-kappa B, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mutation, MESH : Transfection, MESH: Mutation, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunoblotting, Molecular Sequence Data, MESH : Luciferases, Renilla, MESH : DNA Mutational Analysis, Biology, MESH: Sequence Homology, Nucleic Acid, MESH : B-Lymphocytes, Cell Line, Viral Matrix Proteins, 03 medical and health sciences, MESH: Oncogene Proteins, stomatognathic system, MESH : Genetic Variation, Sequence Homology, Nucleic Acid, MESH: B-Lymphocytes, medicine, otorhinolaryngologic diseases, MESH: Recombinant Fusion Proteins, Animals, Humans, Hodgkin's Lymphoma, MESH : Sequence Homology, Nucleic Acid, MESH: Tumor Cells, Cultured, Luciferases, Renilla, 030304 developmental biology, MESH: Viral Matrix Proteins, MESH: Molecular Sequence Data, MESH: Humans, MESH : Reed-Sternberg Cells, Base Sequence, MESH: Apoptosis, MESH: Transfection, MESH : Humans, Genetic Variation, medicine.disease, Hodgkin's lymphoma, Epstein–Barr virus, Lymphoma, MESH: Cell Line, stomatognathic diseases, Reed–Sternberg cell, Cell culture, Cancer research, MESH : Base Sequence, MESH : Animals, Carcinogenesis, MESH : Apoptosis
Abstract: International audience; BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells.
Published: 2009

33. Placental and fetal steroidogenesis

Author: Sanderson , J Thomas, Institut Armand Frappier ( INRS-IAF ), and Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier
Subjects: MESH : Pregnancy, MESH : RNA, Messenger, MESH : Tumor Cells, Cultured, MESH : Placenta, MESH : Humans, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, MESH : Aromatase, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Base Sequence, MESH : DNA Primers, MESH : Female, MESH : Fetus, MESH : Steroids
Abstract: International audience; Steroid hormones are essential for maintenance of pregnancy and fetal development. The expression and catalytic activity of the key steroidogenic enzymes involved in the production of progesterone and estrogens increase during pregnancy, and there is an intricate communication between the mother, the placenta, and the fetus in order to maintain a balanced supply of the steroid hormones essential for embryogenesis. This chapter describes methods for the measurement of the expression and catalytic activity of three key cytochrome P450 (CYP) enzymes involved in the production of progesterone and estrogens, aromatase (CYP19), steroid 17-hydroxylase/17,20-lyase (CYP17), and cholesterol side-chain cleavage (CYP11A).
Published: 2009

34. Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

Author: David Mabey, Dominic P. Kwiatkowski, Gaia Luoni, Matthew J. Burton, Hassan Joof, Kirk A. Rockett, Robin L. Bailey, Martin J. Holland, Jeremy Hull, Angels Natividad, BMC, Ed., London School of Hygiene and Tropical Medicine (LSHTM), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Medical Research Council Laboratories, This work was supported by the Medical Research Council, UK and The Wellcome Trust, UK., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), University of Oxford [Oxford], London School of Hygiene and Tropical Medicine ( LSHTM ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Wellcome Trust Centre for Human Genetics
Subjects: Male, MESH : Aged, MESH: Base Sequence, Blindness, Linkage Disequilibrium, MESH: Blindness, MESH : Child, MESH : Gambia, MESH: Child, MESH: Epistasis, Genetic, Genetics(clinical), MESH: Genetic Variation, Child, Aged, 80 and over, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH : Trachoma, MESH: Granulocyte-Macrophage Colony-Stimulating Factor, MESH : Granulocyte-Macrophage Colony-Stimulating Factor, MESH: Case-Control Studies, 3. Good health, MESH: Linkage Disequilibrium, MESH: Young Adult, Child, Preschool, Chromosomes, Human, Pair 5, Gambia, Chromosomes, Human, Pair 4, MESH: Trachoma, MESH : Case-Control Studies, MESH : Young Adult, Locus (genetics), 03 medical and health sciences, Cicatrix, MESH : Adolescent, Genetics, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, education, lcsh:RC31-1245, MESH : Haplotypes, Trichiasis, Alleles, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, 030306 microbiology, MESH : Humans, MESH: Child, Preschool, Genetic Variation, Epistasis, Genetic, MESH: Adult, MESH: Matrix Metalloproteinase 9, MESH: Haplotypes, MESH : Cicatrix, medicine.disease, Immunity, Innate, MESH: Interleukin-8, Case-Control Studies, MESH : Blindness, Immunology, MESH : Alleles, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Chlamydia trachomatis, MESH: Female, Linkage disequilibrium, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, medicine.disease_cause, MESH : Chromosomes, Human, Pair 5, MESH: Aged, 80 and over, MESH : Chromosomes, Human, Pair 4, Risk Factors, MESH: Risk Factors, MESH : Female, MESH : Matrix Metalloproteinase 9, Genetics (clinical), Keratoconjunctivitis, MESH : Epistasis, Genetic, MESH: Aged, MESH : Linkage Disequilibrium, MESH : Polymorphism, Single Nucleotide, MESH : Adult, MESH : Immunity, Innate, Middle Aged, MESH : Risk Factors, Trachoma, Matrix Metalloproteinase 9, Female, MESH: Immunity, Innate, Adult, MESH: Chromosomes, Human, Pair 5, MESH : Interleukin-8, lcsh:Internal medicine, MESH: Chromosomes, Human, Pair 4, Adolescent, lcsh:QH426-470, MESH : Male, Population, Biology, Polymorphism, Single Nucleotide, Young Adult, MESH : Genetic Variation, Research article, medicine, Allele, 030304 developmental biology, MESH: Cicatrix, Base Sequence, MESH: Alleles, Interleukin-8, Granulocyte-Macrophage Colony-Stimulating Factor, MESH: Male, lcsh:Genetics, MESH: Gambia, Haplotypes, MESH : Base Sequence
Abstract: Background: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. Methods: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses. Results: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. Conclusion: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma.
Published: 2009

35. NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis

Author: Coralie Mouzé-Soulama, Stéphanie Floquet, Daniel R. Brown, Vladimir Pelicic, Helen A. Ewles, David Vallenet, Aurélie Lajus, Philippe Glaser, Christophe Rusniok, Carmen Buchrieser, Claudine Médigue, Génomique des Microorganismes Pathogènes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-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)-Université Paris-Saclay-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)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imperial College London, INSERM, Institut Pasteur/CHU Necker-Enfants Malades, MRT and ANR, BMC, Ed., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Department of Microbiology, CMMI, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Génomique métabolique ( UMR 8030 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Pathogénie des infections systémiques ( UMR_S 570 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Sequence Analysis, DNA, Colony Count, Microbial, Fluorescent Antibody Technique, Human pathogen, [SDV.GEN] Life Sciences [q-bio]/Genetics, Neisseria meningitidis, MESH: Base Sequence, MESH: Virulence, medicine.disease_cause, Genome, Nasopharynx, MESH : Bacterial Proteins, MESH: Bacterial Proteins, MESH: Fluorescent Antibody Technique, MESH: Microbial Viability, Genetics, 0303 health sciences, Virulence, MESH : Genes, Bacterial, MESH: Genomics, MESH : Virulence, Genomics, 3. Good health, MESH: DNA Transposable Elements, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Multigene Family, MESH : DNA Transposable Elements, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Software, MESH : Mutation, MESH: Genes, Bacterial, MESH: Mutation, Sequence analysis, MESH : Colony Count, Microbial, MESH : Multigene Family, Biology, MESH: Sequence Homology, Nucleic Acid, MESH: Neisseria meningitidis, Bacterial genetics, 03 medical and health sciences, MESH: Software, Bacterial Proteins, Sequence Homology, Nucleic Acid, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, MESH : Sequence Homology, Nucleic Acid, Gene, MESH: Colony Count, Microbial, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Microbial Viability, MESH: Humans, Base Sequence, 030306 microbiology, MESH : Neisseria meningitidis, Research, MESH : Genomics, MESH : Humans, MESH : Microbial Viability, Sequence Analysis, DNA, Human genetics, MESH: Nasopharynx, MESH : Fluorescent Antibody Technique, Genes, Bacterial, Mutation, DNA Transposable Elements, MESH : Nasopharynx, MESH: Multigene Family, MESH : Base Sequence, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Software, MESH : Sequence Analysis, DNA
Abstract: The genome of a clinical isolate of Neisseria meningitidis is described. This and other reannotated Neisseria genomes are compiled in a database., Background Genome sequences, now available for most pathogens, hold promise for the rational design of new therapies. However, biological resources for genome-scale identification of gene function (notably genes involved in pathogenesis) and/or genes essential for cell viability, which are necessary to achieve this goal, are often sorely lacking. This holds true for Neisseria meningitidis, one of the most feared human bacterial pathogens that causes meningitis and septicemia. Results By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization. Conclusions By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies.
Published: 2009

36. Probing mRNA structure and sRNA-mRNA interactions in bacteria using enzymes and lead(II)

Author: Chevalier, Clément, Geissmann, Thomas, Helfer, Anne-Catherine, Romby, Pascale, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), and Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Staphylococcus aureus, RNA, Untranslated, MESH : RNA, Messenger, MESH : RNA, Untranslated, MESH : Molecular Sequence Data, Molecular Sequence Data, MESH : Nucleic Acid Conformation, MESH: Enzymes, MESH : Enzymes, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Chemical Fractionation, MESH: Base Sequence, MESH: RNA, Untranslated, MESH: Chemical Fractionation, MESH : Hydrolysis, MESH: RNA, MESH : RNA, MESH: Staphylococcus aureus, RNA, Messenger, Molecular Biology, MESH: RNA, Messenger, MESH: Molecular Sequence Data, Base Sequence, MESH : Chemical Fractionation, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Hydrolysis, MESH : Staphylococcus aureus, MESH: Molecular Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH : Molecular Biology, MESH : RNA, Bacterial, Enzymes, RNA, Bacterial, MESH: Nucleic Acid Conformation, Lead, Nucleic Acid Conformation, RNA, MESH : Base Sequence, MESH : Lead, MESH: RNA, Bacterial, MESH: Hydrolysis, MESH: Lead
Abstract: International audience; Enzymatic probing and lead(II)-induced cleavages have been developed to study the secondary structure of RNA molecules either free or engaged in complex with different ligands. Using a combination of probes with different specificities (unpaired vs. paired regions), it is possible to get information on the accessibility of each nucleotide, on the binding site of a ligand (noncoding RNAs, protein, metabolites), and on RNA conformational changes that accompanied ligand binding or environmental conditions (temperature, pH, ions, etc.). The detection of the cleavages can be conducted by two different ways, which are chosen according to the length of the studied RNA. The first method uses end-labeled RNA molecules and the second one involves primer extension by reverse transcriptase. We provide here an experimental procedure that was designed to map the structure of mRNA and mRNA-sRNA interaction in vitro.
Published: 2009

37. Ribosomal initiation complexes probed by toeprinting and effect of trans-acting translational regulators in bacteria

Author: Fechter, Pierre, Chevalier, Clément, Yusupova, Gulnara, Yusupov, Marat, Romby, Pascale, Marzi, Stefano, Architecture et réactivité de l'ARN ( ARN ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Peptide Chain Initiation, Translational, Staphylococcus aureus, MESH : Escherichia coli, Toeprinting, MESH : Molecular Sequence Data, mRNA, Molecular Sequence Data, MESH: Thermus thermophilus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Base Sequence, MESH : Thermus thermophilus, Ribosome purification, Bacterial Proteins, Translation initiation, MESH: Staphylococcus aureus, Escherichia coli, MESH : Bacterial Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Bacteria, Peptide Chain Initiation, Translational, MESH: Bacterial Proteins, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Translational regulator, MESH : Ribosomes, MESH: Molecular Sequence Data, Bacteria, Base Sequence, MESH: Escherichia coli, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Thermus thermophilus, MESH : Staphylococcus aureus, MESH: Molecular Biology, MESH : Molecular Biology, MESH : RNA, Bacterial, Ribosome, MESH: Bacteria, RNA, Bacterial, MESH : Base Sequence, MESH: RNA, Bacterial, MESH: Ribosomes, Ribosomes, MESH : Peptide Chain Initiation, Translational
Abstract: International audience; Toeprinting was developed to study the formation of ribosomal initiation complexes in bacteria. This approach, based on the inhibition of reverse transcriptase elongation, was used to monitor the effect of ribosomal components and translational factors on the formation of the active ribosomal initiation complex. Moreover, this method offers an easy way to study in vitro how mRNA conformational changes alter ribosome binding at the initiation site. These changes can be induced either by environmental cues (temperature, ion concentration), or by the binding of metabolites, regulatory proteins, and trans-acting RNAs. An experimental guide is given to follow the different steps of the formation of ribosomal initiation complexes in Escherichia coli and Staphylococcus aureus, and to monitor the mechanism of action of several regulators on translation initiation in vitro. Protocols to prepare the ribosome and the subunits are also given for Thermus thermophilus, Staphylococcus aureus, and Escherichia coli.
Published: 2009

38. A combination of transposable elements and magnetic cell sorting provides a very efficient transgenesis system for chicken primary erythroid progenitors

Author: Koichi Kawakami, Camila Mejia-Pous, Olivier Gandrillon, Joanna Koszela, José Viñuelas, Claudine Faure, Yoshiko Takahashi, Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Department of Geophysics [Sendai], Tohoku University [Sendai], LNCC, the CNRS, the UCBL, the Region Rhône Alpes, the IXXI and the ARC, Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Biologie Fonctionnelle, Insectes et Interactions ( BF2I ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA )
Subjects: MESH : DNA, Complementary, MESH: Immunotherapy, Cell Separation, MESH: Base Sequence, Polymerase Chain Reaction, Retrovirus, MESH: Genetic Vectors, Complementary, MESH: Animals, Transgenes, MESH : Polymerase Chain Reaction, Erythroid Precursor Cells, Cells, Cultured, Genetics, MESH : Immunoglobulin Fc Fragments, biology, Methodology Article, Cell sorting, MESH : Genetic Vectors, Cell biology, Transgenesis, MESH : Immunotherapy, MESH: Immunization, Immunotherapy, SDV:BBM:BM, Stem cell, Biotechnology, Plasmids, Transposable element, Animals, Base Sequence, Cloning, Molecular, DNA, Genetic Vectors, Immunization, Immunoglobulin Fc Fragments, Recombinant Fusion Proteins, Solubility, Cell type, MESH : Cloning, Molecular, MESH : Recombinant Fusion Proteins, lcsh:Biotechnology, Transgene, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Transfection, MESH: Immunoglobulin Fc Fragments, lcsh:TP248.13-248.65, MESH: Recombinant Fusion Proteins, MESH: Cloning, Molecular, MESH : Solubility, MESH: Polymerase Chain Reaction, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH : Immunization, MESH: DNA, Complementary, biology.organism_classification, MESH: Solubility, Mutagenesis, Insertional, DNA Transposable Elements, MESH : Base Sequence, MESH : Animals, Chickens
Abstract: Background Stable transgenesis is an undeniable key to understanding any genetic system. Retrovirus-based insertional strategies, which feature several technical challenges when they are used, are often limited to one particular species, and even sometimes to a particular cell type as the infection depends on certain cellular receptors. A universal-like system, which would allow both stable transgene expression independent of the cell type and an efficient sorting of transfected cells, is required when handling cellular models that are incompatible with retroviral strategies. Results We report here on the combination of a stable insertional transgenesis technique, based on the Tol2 transposon system together with the magnetic cell sorting (MACS) technique, which allows specific selection of cells carrying the transgene in an efficient, reliable and rapid way. Conclusion This new Tol2/MACS system leads to stable expression in a culture of primary chicken erythroid cells highly enriched in cells expressing the transgene of interest. This system could be used in a wide variety of vertebrate species.
Published: 2009

39. In vivo and ex vivo gene transfer in thymocytes and thymocyte precursors

Author: Adjali , Oumeya, Montel-Hagen , Amélie, Swainson , Louise, Marty , Sophie, Vicente , Rita, Mongellaz , Cedric, Jacquet , Chantal, Zimmermann , Valérie, Taylor , Naomi, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Cell Line, MESH: DNA Primers, MESH: Gene Transfer Techniques, Antigens, CD34, MESH : Transduction, Genetic, Thymus Gland, MESH: Base Sequence, Cell Line, Mice, Transduction, Genetic, MESH : Mice, Animals, Humans, MESH : Thymus Gland, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Gene Transfer Techniques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, DNA Primers, MESH: Humans, Base Sequence, MESH : Humans, Gene Transfer Techniques, MESH: Antigens, CD34, MESH: Thymus Gland, MESH: Transduction, Genetic, MESH: Cell Line, MESH : Antigens, CD34, MESH : Base Sequence, MESH : DNA Primers, MESH : Animals
Abstract: International audience; The thymus provides a specialized environment allowing the differentiation of T lymphocytes from bone marrow-derived progenitor cells. We and others have demonstrated that gene transfer into distinct thymocyte populations can be obtained, both in vivo and ex vivo, using lentiviral vectors. Here, we describe techniques for intrathymic lentiviral transduction in mice, using a surgical approach wherein the thoracic cavity is exposed as well as a significantly less invasive strategy wherein virions are directly injected through the skin. Moreover, thymocyte differentiation from murine and human progenitors is now feasible in vitro, under conditions wherein the Notch and IL-7 signaling pathways are activated. We describe methods allowing transduction of murine and human progenitors and their subsequent differentiation into more mature thymocytes. Conditions for lentiviral gene transfer into more differentiated human thymocyte subsets are also presented. Optimization of technologies for HIV-based gene transfer into murine and human thymocyte progenitors will advance strategies aimed at modulating T-cell differentiation and function in-vivo; approaches potentially targeting patients with genetic and acquired immunodeficiencies as well as immune-sensitive tumors. Furthermore, this technology will foster the progression of basic research aimed at elucidating molecular aspects of T-cell differentiation in mice and humans.
Published: 2008

40. Epidemiological surveillance of mycoplasmas belonging to the 'Mycoplasma mycoides' cluster: is DGGE fingerprinting of 16S rRNA genes suitable?

Author: Laure Maigre, François Poumarat, A. Tricot, Florence Tardy, Patrice Gaurivaud, Laboratoire d'études et de recherches en pathologie bovine et hygiène des viandes, AFSSA, Mycoplasmoses des ruminants [Lyon], Université de Lyon-VetAgro Sup ( VAS ), Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Mycoplasmoses des Ruminants - UMR (MYCO), and Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)
Subjects: MESH : Mycoplasma Infections, MESH : Molecular Sequence Data, 16SrRNA gene, MESH: Base Sequence, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, Applied Microbiology and Biotechnology, strains detection and identification, MESH: Mycoplasma, Mycoplasma, MESH : Cattle, RNA, Ribosomal, 16S, MESH: Cattle Diseases, MESH: DNA Fingerprinting, MESH : DNA, Ribosomal, MESH : DNA, Bacterial, MESH: Animals, 1UMYCOPLASME, DGGE, MESH: Phylogeny, Phylogeny, MESH: DNA, Ribosomal, biology, Phylogenetic tree, MESH : Sequence Alignment, Goats, epidemiological surveillance, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : DNA Fingerprinting, MESH: RNA, Ribosomal, 16S, MESH: Cattle, "Mycoplasma mycoides" cluster, Electrophoresis, Polyacrylamide Gel, Mycoplasma mycoides, Temperature gradient gel electrophoresis, DNA, Bacterial, Sequence analysis, Molecular Sequence Data, MESH: Sequence Alignment, Cattle Diseases, MESH : Goat Diseases, MESH: Goat Diseases, MESH : Electrophoresis, Polyacrylamide Gel, MESH: Goats, DNA, Ribosomal, MYCOPLASME, Microbiology, Phylogenetics, medicine, Animals, Humans, Mycoplasma Infections, MESH : Cattle Diseases, MESH: Humans, MESH: Molecular Sequence Data, MESH : Mycoplasma, Goat Diseases, Base Sequence, MESH : Humans, MESH : Phylogeny, Ribosomal RNA, MESH: Mycoplasma Infections, biology.organism_classification, 16S ribosomal RNA, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, DNA Fingerprinting, MESH : RNA, Ribosomal, 16S, MESH : Goats, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mycoplasma mycoides" cluster, MESH : Base Sequence, Cattle, MESH : Animals, Sequence Alignment, MESH: Electrophoresis, Polyacrylamide Gel
Abstract: Aims: The analysis by Denaturing Gradient Gel Electrophoresis (DGGE) of the PCR-amplified V3 region of 16S rRNA gene was previously shown to detect and differentiate a large number of human and animal mycoplasmas. In this study, we further assessed the suitability of the technique for epidemiological surveillance of mycoplasmas belonging to the ‘Mycoplasma mycoides’ cluster, a phylogenetic group that includes major ruminant pathogens. Methods and Results: The V3 region of 16S rRNA genes from approx. 50 field strains was amplified and analysed by DGGE. Detection and identification results were compared with the ones obtained by antigenic testing and sequence analysis. Conclusions: The DGGE technique is robust and valuable as a first-line test, but the patterns obtained for strains belonging to the ‘M. mycoides’ cluster were too variable within a taxon and in contrast too conserved between taxa to allow an unequivocal identification of isolates without further analysis. Significance and Impact of the Study: Issues raised by the quest for a single universal test able to detect and identify any mycoplasma in one clinical sample are thoroughly documented.
Published: 2008

41. Aichi virus, norovirus, astrovirus, enterovirus, and rotavirus involved in clinical cases from a French oyster-related gastroenteritis outbreak

Author: Katia Ambert-Balay, Robert L. Atmar, Ophelie Serais, Monique Pommepuy, Sylvain Parnaudeau, H. Giraudon, Joanna Krol, G Delmas, Jean-Claude Le Saux, Françoise S. Le Guyader, Pierre Pothier, Laboratoire de Microbiologie, IFREMER, Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ), Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Laboratoire de sérologie-virologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), Université de Bourgogne (UB), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: Male, Rotavirus, Oyster, MESH : Molecular Sequence Data, Epidemiology, viruses, MESH: Base Sequence, medicine.disease_cause, MESH : Kobuvirus, Disease Outbreaks, Feces, MESH: Animals, MESH : Female, MESH: Disease Outbreaks, Enterovirus, 0303 health sciences, MESH: Middle Aged, biology, MESH: Kobuvirus, MESH : Sequence Alignment, MESH: Enterovirus, MESH: Feces, food and beverages, MESH: Rotavirus, Middle Aged, MESH : Adult, Gastroenteritis, 3. Good health, MESH : Gastroenteritis, MESH: Virus Diseases, Virus Diseases, MESH: RNA, Viral, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Female, MESH : Enterovirus, France, Aichi virus, Adult, Microbiology (medical), MESH: Norovirus, Kobuvirus, MESH : Male, MESH : Rotavirus, Molecular Sequence Data, MESH: Sequence Alignment, Reoviridae, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Ostreidae, Microbiology, Astrovirus, 03 medical and health sciences, biology.animal, medicine, Animals, Humans, MESH : RNA, Viral, MESH : Middle Aged, MESH : Disease Outbreaks, MESH : France, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, MESH : Ostreidae, Base Sequence, 030306 microbiology, MESH : Norovirus, Norovirus, MESH : Humans, MESH: Adult, MESH : Feces, biology.organism_classification, MESH : Virus Diseases, Ostreidae, Virology, Caliciviridae, MESH: Male, MESH: Gastroenteritis, MESH: France, MESH : Base Sequence, MESH : Animals, Sequence Alignment, MESH: Female
Abstract: Following a flooding event close to a shellfish production lagoon, 205 cases of gastroenteritis were linked to oyster consumption. Twelve stool samples from different individuals were collected. Analysis showed that eight samples were positive for multiple enteric viruses, and one stool sample had seven different enteric viruses. Analysis of shellfish implicated in the outbreak allowed detection of the same diversity of enteric viruses, with some viral genomic sequences being identical to those obtained from stool sample analysis. Shellfish were contaminated by as many as five different enteric viruses. For the first time in Europe, Aichi virus was identified in oyster samples. Shellfish samples collected over 3 weeks following the outbreak showed a progressive decline in the level of virus contamination as measured by the virus diversity detected and by quantitative reverse transcription-PCR.
Published: 2008

42. Production of biologically active forms of recombinant hepcidin, the iron-regulatory hormone

Author: Gagliardo, Bruno, Faye, Audrey, Jaouen, Maryse, Deschemin, Jean-Christophe, Canonne-Hergaux, François, Vaulont, Sophie, Sari, Marie-Agnès, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de métallurgie physique (LMP), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Génétique et pathologie moléculaires, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), 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 de génétique moléculaire (CGM), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Dakar-Réseau International des Instituts Pasteur ( RIIP ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de métallurgie physique ( LMP ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Chimie des Substances Naturelles ( ICSN ), Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), 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 de génétique moléculaire ( CGM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: inorganic chemicals, MESH: DNA Primers, MESH : Recombinant Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Base Sequence, MESH: Iron-Regulatory Proteins, MESH : Electrophoresis, Polyacrylamide Gel, Mass Spectrometry, MESH: Recombinant Proteins, Mice, MESH : Chromatography, High Pressure Liquid, MESH : Mass Spectrometry, Hepcidins, hemic and lymphatic diseases, MESH : Mice, Animals, Humans, MESH: Animals, MESH: Chromatography, High Pressure Liquid, MESH: Mice, Chromatography, High Pressure Liquid, DNA Primers, MESH: Mass Spectrometry, MESH: Humans, Base Sequence, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Humans, MESH: Antimicrobial Cationic Peptides, Iron-Regulatory Proteins, nutritional and metabolic diseases, MESH : Iron-Regulatory Proteins, MESH : Antimicrobial Cationic Peptides, Recombinant Proteins, Electrophoresis, Polyacrylamide Gel, MESH : Base Sequence, MESH : DNA Primers, MESH : Animals, Antimicrobial Cationic Peptides, MESH: Electrophoresis, Polyacrylamide Gel
Abstract: International audience; Hepcidin is a liver produced cysteine-rich peptide hormone that acts as the central regulator of body iron metabolism. Hepcidin is synthesized under the form of a precursor, prohepcidin, which is processed to produce the biologically active mature 25 amino acid peptide. This peptide is secreted and acts by controlling the concentration of the membrane iron exporter ferroportin on intestinal enterocytes and macrophages. Hepcidin binds to ferroportin, inducing its internalization and degradation, thus regulating the export of iron from cells to plasma. The aim of the present study was to develop a novel method to produce human and mouse recombinant hepcidins, and to compare their biological activity towards their natural receptor ferroportin. Hepcidins were expressed in Escherichia coli as thioredoxin fusion proteins. The corresponding peptides, purified after cleavage from thioredoxin, were properly folded and contained the expected four-disulfide bridges without the need of any renaturation or oxidation steps. Human and mouse hepcidins were found to be biologically active, promoting ferroportin degradation in macrophages. Importantly, biologically inactive aggregated forms of hepcidin were observed depending on purification and storage conditions, but such forms were unrelated to disulfide bridge formation.
Published: 2008

43. Tetrameric and homodimeric camelid IgGs originate from the same IgH locus

Author: Pierre Lafaye, Patricia Cavelier, Ikbel Achour, François Rougeon, Christiane Bouchier, Magali Tichit, Génétique et Biochimie du Développement, Institut Pasteur [Paris]-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 ), Génomique (Plate-Forme), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-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), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: MESH: Immunoglobulins, MESH : Molecular Sequence Data, MESH: Amino Acid Sequence, MESH: Base Sequence, MESH : Immunoglobulins, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, MESH: Phylogeny, Peptide sequence, Phylogeny, Genetics, 0303 health sciences, B-Lymphocytes, biology, MESH : Amino Acid Sequence, MESH: Camels, MESH : Protein Binding, Translocon, medicine.anatomical_structure, MESH : Dimerization, Cosmid, MESH: Camelids, New World, Antibody, Camelids, New World, Dimerization, Protein Binding, Camelus, MESH : Cell Membrane, Immunology, Molecular Sequence Data, Immunoglobulins, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH : B-Lymphocytes, 03 medical and health sciences, Complementary DNA, MESH: B-Lymphocytes, medicine, MESH: Protein Binding, Animals, Amino Acid Sequence, Gene, B cell, 030304 developmental biology, MESH: Molecular Sequence Data, MESH : Camels, Base Sequence, Cell Membrane, MESH : Phylogeny, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Molecular biology, MESH : Camelids, New World, Chromosome 4, MESH: Dimerization, biology.protein, MESH : Base Sequence, MESH : Animals, 030215 immunology, MESH: Cell Membrane
Abstract: In addition to producing conventional tetrameric IgGs, camelids have the particularity of producing a functional homodimeric IgG type lacking L (light) chains and only made up of two H (heavy) chains. This nonconventional IgG type is characterized by variable and constant regions referred to as VHH and CHH, respectively, and which differ from conventional VH and CH counterparts. Although the structural properties of homodimeric IgGs have been well investigated, the genetic bases involved in their generation are still largely unknown. In this study, we characterized the organization of genes coding for the H chains of tetrameric and homodimeric IgGs by constructing an alpaca (Lama pacos) genomic cosmid library. We showed that a single IgH locus in alpaca chromosome 4 contains all of the genetic elements required for the generation of the two types of Igs. The alpaca IgH locus is composed of a V region that contains both VHH and VH genes followed by a unique DH-JH cluster and C region genes, which include both CHH and CH genes. Although this general gene organization greatly resembles that of other typical mammalian Vn-Dn-Jn-Cn translocon IgH loci, the intermixed gene organization within the alpaca V and C regions reveals a new type of translocon IgH locus. Furthermore, analyses of cDNA coding for the membrane forms of IgG and IgM present in alpaca peripheral blood B cells are most consistent with the notion that the development of a B cell bearing homodimeric IgG passes through an IgM+ stage, similar to the case for conventional IgG.
Published: 2008

44. Diversity surveys and evolutionary relationships of aoxB genes in aerobic arsenite-oxidizing bacteria

Author: Marianne Quéméneur, Michel Jauzein, Audrey Heinrich-Salmeron, Didier Lièvremont, Catherine Joulian, Daniel Muller, Philippe N. Bertin, Francis Garrido, Génétique moléculaire, génomique, microbiologie (GMGM), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire de Biologie Tumorale, CRLCC Paul Strauss, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Génétique moléculaire, génomique, microbiologie ( GMGM ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), XLIM ( XLIM ), Université de Limoges ( UNILIM ) -Centre National de la Recherche Scientifique ( CNRS ), and Bureau de Recherches Géologiques et Minières (BRGM) ( BRGM )
Subjects: Chemoautotrophic Growth, MESH: Sequence Analysis, Protein, MESH: Amino Acid Sequence, MESH: Base Sequence, Polymerase Chain Reaction, MESH : Arsenites, Conserved sequence, Sequence Analysis, Protein, RNA, Ribosomal, 16S, MESH : Genetic Markers, MESH : DNA, Bacterial, Soil Pollutants, MESH: Genetic Variation, MESH: Phylogeny, MESH : Proteobacteria, Phylogeny, 0303 health sciences, MESH: Conserved Sequence, MESH : Amino Acid Sequence, MESH : Genes, Bacterial, Bacterial, MESH : Oxidoreductases, MESH: RNA, Ribosomal, 16S, MESH : DNA Primers, MESH: Arsenites, Proteobacteria, Genetic Markers, MESH: DNA Primers, 16S, Sequence analysis, Arsenites, MESH : Soil Microbiology, Molecular Sequence Data, MESH: Biodiversity, 03 medical and health sciences, Phylogenetics, MESH : Conserved Sequence, MESH : Bacteria, Amino Acid Sequence, MESH: Oxidoreductases, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Oxidation-Reduction, Ribosomal, MESH: Soil Pollutants, MESH: Molecular Sequence Data, Bacteria, 030306 microbiology, Alphaproteobacteria, Genetic Variation, MESH: Polymerase Chain Reaction, DNA, Ribosomal RNA, MESH: DNA, Bacterial, Genes, MESH : Sequence Analysis, Protein, MESH : Sequence Analysis, DNA, MESH: Oxidation-Reduction, MESH: Sequence Analysis, DNA, MESH : Molecular Sequence Data, MESH: Genetic Markers, Applied Microbiology and Biotechnology, MESH : Soil Pollutants, MESH : Biodiversity, MESH : Polymerase Chain Reaction, Betaproteobacteria, Conserved Sequence, Soil Microbiology, Genetics, Ecology, biology, Biodiversity, MESH: Genes, Bacterial, Oxidoreductases, Oxidation-Reduction, Sequence Analysis, Biotechnology, DNA, Bacterial, MESH : Chemoautotrophic Growth, Microbial Ecology, MESH : Genetic Variation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, DNA Primers, Base Sequence, Protein, MESH : Phylogeny, Sequence Analysis, DNA, MESH: Proteobacteria, biology.organism_classification, 16S ribosomal RNA, MESH: Chemoautotrophic Growth, MESH : RNA, Ribosomal, 16S, MESH: Bacteria, MESH: Soil Microbiology, Genes, Bacterial, RNA, MESH : Base Sequence, Food Science
Abstract: A new primer set was designed to specifically amplify ca. 1,100 bp of aoxB genes encoding the As(III) oxidase catalytic subunit from taxonomically diverse aerobic As(III)-oxidizing bacteria. Comparative analysis of AoxB protein sequences showed variable conservation levels and highlighted the conservation of essential amino acids and structural motifs. AoxB phylogeny of pure strains showed well-discriminated taxonomic groups and was similar to 16S rRNA phylogeny. Alphaproteobacteria -, Betaproteobacteria -, and Gammaproteobacteria -related sequences were retrieved from environmental surveys, demonstrating their prevalence in mesophilic As-contaminated soils. Our study underlines the usefulness of the aoxB gene as a functional marker of aerobic As(III) oxidizers.
Published: 2008

45. Distinct effects of DNA-PKcs and Artemis inactivation on signal joint formation in vivo

Author: Evelyne Jouvin-Marche, Cédric Touvrey, Serge M. Candéias, Chrystelle Couedel, Jean-Pierre de Villartay, Maria Jasin, Pauline Soulas, Rachel Couderc, Patrice N. Marche, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developmental Biology Program, Memorial Sloane Kettering Cancer Center [New York], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-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), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Memorial Sloan Kettering Cancer Center, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Lésions des Acides Nucléiques ( LAN ), Service de Chimie Inorganique et Biologique ( SCIB - UMR E3 ), Institut Nanosciences et Cryogénie ( INAC ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut Nanosciences et Cryogénie ( INAC ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes ( UGA ) -Centre National de la Recherche Scientifique ( CNRS ), Candéias, Serge, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG)
Subjects: Protein kinase complex, MESH : Molecular Sequence Data, MESH : DNA, MESH : Lymphocytes, DNA-Activated Protein Kinase, Mice, SCID, MESH: Base Sequence, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Artemis, Mice, 0302 clinical medicine, MESH: Endonucleases, MESH : Antigens, Nuclear, MESH : Endonucleases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Lymphocytes, MESH: Mice, SCID, MESH : DNA-Activated Protein Kinase, DNA-PKcs, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, biology, V(D)J recombination, MESH: DNA, Nuclear Proteins, Antigens, Nuclear, T cell receptor genes, Junctional diversity, DNA-Binding Proteins, Non-homologous end joining, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : DNA-Binding Proteins, MESH: Enzyme Activation, [SDV.IMM] Life Sciences [q-bio]/Immunology, Molecular Sequence Data, Immunology, MESH : Mice, Inbred C57BL, 03 medical and health sciences, MESH: Mice, Inbred C57BL, signal joints, MESH : Mice, Animals, Protein kinase A, MESH: Antigens, Nuclear, MESH: Mice, Ku Autoantigen, Molecular Biology, 030304 developmental biology, Nuclease, MESH: Molecular Sequence Data, Base Sequence, MESH : Nuclear Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Endonucleases, Molecular biology, MESH : Mice, SCID, Enzyme Activation, Mice, Inbred C57BL, MESH: DNA-Activated Protein Kinase, biology.protein, MESH: Lymphocytes, MESH : Base Sequence, MESH : Animals, Homologous recombination, MESH : Enzyme Activation, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins, 030217 neurology & neurosurgery
Abstract: International audience; The assembly of functional immune receptor genes via V(D)J recombination in developing lymphocytes generates DNA double-stranded breaks intermediates that are repaired by non-homologous end joining (NHEJ). This repair pathway requires the sequential recruitment and activation onto coding and signal DNA ends of several proteins, including the DNA-dependent protein kinase and the nuclease Artemis. Artemis activity, triggered by the DNA-dependent protein kinase, is necessary to process the genes hairpin-sealed coding ends but appears dispensable for the ligation of the reciprocal phosphorylated, blunt-ended signal ends into a signal joint. The DNA-dependent protein kinase is however present on signal ends and could potentially recruit and activate Artemis during signal joint formation. To determine whether Artemis plays a role during the resolution of signal ends during V(D)J recombination, we analyzed the structure of signal joints generated in developing thymocytes during the rearrangement of T cell receptor genes in wild type mice and mice mutated for NHEJ factors. These joints exhibit junctional diversity resulting from N nucleotide polymerization by the terminal nucleotidyl transferase and nucleotide loss from one or both of the signal ends before they are ligated. Our results show that Artemis participates in the repair of signal ends in vivo. Furthermore, our results also show that while the DNA-dependent protein kinase complex protects signal ends from processing, including deletions, Artemis seems on the opposite to promote their accessibility to modifying enzymes. In addition, these data suggest that Artemis might be the nuclease responsible for nucleotide loss from signal ends during the repair process.
Published: 2008

46. MicroRNA166 controls root and nodule development in Medicago truncatula

Author: Carole Laffont, Martin Crespi, Andreas Niebel, Julie Plet, Philippe Laporte, Jean-Philippe Combier, Mariana Jovanovic, Florian Frugier, Adnane Boualem, Institut des sciences du végétal (ISV), Centre National de la Recherche Scientifique (CNRS), Nouveaux Outils pour La Coopération et l'Education (NOCE), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Laboratoire des interactions plantes micro-organismes (LIPM), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut des sciences du végétal ( ISV ), Centre National de la Recherche Scientifique ( CNRS ), Nouveaux Outils pour La Coopération et l'Education ( NOCE ), Laboratoire d'Informatique Fondamentale de Lille ( LIFL ), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique ( CNRS ) -Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique ( CNRS ), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Laboratoire des interactions plantes micro-organismes ( LIPMO ), and Institut National de la Recherche Agronomique ( INRA ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0106 biological sciences, MESH : Plant Roots, MESH : Brain Chemistry, MESH: Plant Roots, clustered miRNA, Plant Science, MESH: Amino Acid Sequence, MESH: Base Sequence, 01 natural sciences, MESH : Cattle, MESH: Cattle Diseases, MESH: Animals, In Situ Hybridization, 0303 health sciences, MESH : Amino Acid Sequence, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : In Situ Hybridization, Medicago truncatula, Cell biology, MESH : Proton-Translocating ATPases, MESH : DNA Primers, MESH: Proteolipids, MESH: DNA Primers, MESH: Mitochondria, Organogenesis, MESH: Microscopy, Electron, MESH : Electrophoresis, Polyacrylamide Gel, 03 medical and health sciences, MESH: In Situ Hybridization, microRNA, Botany, Genetics, MESH: Blotting, Northern, MESH: Mass Spectrometry, MESH : Cattle Diseases, MESH: Molecular Sequence Data, MESH : Medicago truncatula, Lateral root, HD ZIP III transcription factors, MESH : Pigments, Biological, MESH: Neuronal Ceroid-Lipofuscinoses, MESH : Brain, MESH : Amino Acids, MESH : Gene Expression Regulation, Plant, MESH: MicroRNAs, MESH: Female, MESH: Liver, [ SDV.BV ] Life Sciences [q-bio]/Vegetal Biology, MESH : Molecular Sequence Data, MESH: Amino Acids, Plant Roots, lateral root, MESH: Proton-Translocating ATPases, Gene Expression Regulation, Plant, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Female, MESH: Brain Chemistry, MESH : Pancreas, MESH: Medicago truncatula, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH : Blotting, Northern, MESH: Pancreas, MESH: Lipoproteins, MESH : Kidney, MESH: Cattle, MESH : Mitochondria, Rhizobium, MESH: Pigments, Biological, Transgene, MESH : Lipoproteins, MESH: Brain, MESH : Mass Spectrometry, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MESH: Gene Expression Regulation, Plant, Transcription factor, Gene, 030304 developmental biology, DNA Primers, Base Sequence, polycistronic miRNA, MESH : Liver, MESH : Lipids, Cell Biology, MESH: Kidney, Meristem, biology.organism_classification, Blotting, Northern, symbiotic nodulation, MESH: Lipids, MESH : Microscopy, Electron, MESH : MicroRNAs, MicroRNAs, MESH : Proteolipids, MESH : Base Sequence, MESH : Animals, MESH : Neuronal Ceroid-Lipofuscinoses, 010606 plant biology & botany, MESH: Electrophoresis, Polyacrylamide Gel
Abstract: International audience; Legume root architecture is characterized by the development of two de novo meristems, leading to the formation of lateral roots or symbiotic nitrogen-fixing nodules. Organogenesis involves networks of transcription factors, the encoding mRNAs of which are frequently targets of microRNA (miRNA) regulation. Most plant miRNAs, in contrast with animal miRNAs, are encoded as single entities in an miRNA precursor. In the model legume Medicago truncatula, we have identified the MtMIR166a precursor containing tandem copies of MIR166 in a single transcriptional unit. These miRNAs post-transcriptionally regulate a new family of transcription factors associated with nodule development, the class-III homeodomain-leucine zipper (HD-ZIP III) genes. In situ expression analysis revealed that these target genes are spatially co-expressed with MIR166 in vascular bundles, and in apical regions of roots and nodules. Overexpression of the tandem miRNA precursor correlated with MIR166 accumulation and the downregulation of several class-III HD-ZIP genes, indicating its functionality. MIR166 overexpression reduced the number of symbiotic nodules and lateral roots, and induced ectopic development of vascular bundles in these transgenic roots. Hence, plant polycistronic miRNA precursors, although rare, can be processed, and MIR166-mediated post-transcriptional regulation is a new regulatory pathway involved in the regulation of legume root architecture.
Published: 2008

47. Ancient DNA evidence for the loss of a highly divergent brown bear clade during historical times

Author: Calvignac, Sébastien, Hughes, Sandrine, Tougard, Christelle, Michaux, Jacques, Thevenot, Michel, Philippe, Michel, Hamdine, Watik, Hänni, Catherine, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de Conservation et d'Étude sur les Collections (CCEC), Muséeum d'Histoire Naturelle, Work supported by the CNRS (eclipse program), University Lyon I and the programme ‘Dynamique évolutive des espèces fractionnées, insulaires et invasives' of the EPHE. Contribution ISEM 2006–085., Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Université Paul-Valéry - Montpellier 3 (UM3)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paul-Valéry - Montpellier 3 (UPVM)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut de Génomique Fonctionnelle de Lyon ( IGFL ), École normale supérieure - Lyon ( ENS Lyon ) -Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences de l'Evolution de Montpellier ( ISEM ), Université de Montpellier ( UM ) -Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique ( CNRS ), Centre d’Ecologie Fonctionnelle et Evolutive ( CEFE ), Université Paul-Valéry - Montpellier 3 ( UM3 ) -Centre international d'études supérieures en sciences agronomiques ( Montpellier SupAgro ) -École pratique des hautes études ( EPHE ) -Institut national de la recherche agronomique [Montpellier] ( INRA Montpellier ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD [France-Sud] ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro ), and Centre de Conservation et d'Étude sur les Collections ( CCEC )
Subjects: MESH : Molecular Sequence Data, MESH : Cytochromes b, MESH: Africa, Northern, brown bear, phylogeography, MESH: Base Sequence, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Polymerase Chain Reaction, MESH: Fossils, MESH: Variation (Genetics), MESH: Extinction, Biological, Africa, Northern, MESH : DNA, Mitochondrial, MESH: Animals, MESH: Phylogeny, MESH : Ursidae, MESH : Polymerase Chain Reaction, Phylogeny, [ SDU.STU.PG ] Sciences of the Universe [physics]/Earth Sciences/Paleontology, MESH : Variation (Genetics), Fossils, mtDNA, MESH : Sequence Alignment, Cytochromes b, MESH: Cytochromes b, MESH : Africa, Northern, [ SDV.GEN.GPO ] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], MESH : Extinction, Biological, [SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology, Ursidae, MESH: Ursidae, Molecular Sequence Data, MESH: Sequence Alignment, Extinction, Biological, DNA, Mitochondrial, Animals, ancient DNA, MESH: Molecular Sequence Data, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Base Sequence, Holocene, MESH: DNA, Mitochondrial, MESH : Phylogeny, Genetic Variation, MESH: Polymerase Chain Reaction, North Africa, MESH : Fossils, MESH : Base Sequence, MESH : Animals, Sequence Alignment, human activities, [ SDV.BID.SPT ] Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy
Abstract: 9 pages; International audience; The genetic diversity of present-day brown bears (Ursus arctos) has been extensively studied over the years and appears to be geographically structured into five main clades. The question of the past diversity of the species has been recently addressed by ancient DNA studies that concluded to a relative genetic stability over the last 35,000 years. However, the post-last glacial maximum genetic diversity of the species still remains poorly documented, notably in the Old World. Here, we analyse Atlas brown bears, which became extinct during the Holocene period. A divergent brown bear mitochondrial DNA lineage not present in any of the previously studied modern or ancient bear samples was uncovered, suggesting that the diversity of U. arctos was larger in the past than it is now. Specifically, a significant portion (with respect to sequence divergence) of the intraspecific diversity of the brown bear was lost with the extinction of the Atlas brown bear after the Pleistocene/Holocene transition.
Published: 2008

48. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy

Author: Sylvie Odent, Jamel Chelly, Christophe Philippe, Thierry Bienvenu, Haydeé Rosas-Vargas, L. Lazaro, B. Girard, C. Gitiaux, Nadia Bahi-Buisson, Juliette Nectoux, Philippe Jonveaux, M. A. N'Guyen Morel, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique médicale, hôpital Sud, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Sud, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-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 Paris Descartes - Paris 5 (UPD5), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: MESH : RNA, Messenger, MESH: Sequence Homology, Amino Acid, Mutant, CDKL5, MESH: Brain Diseases, Metabolic, Inborn, MESH: Amino Acid Sequence, MESH : Child, Preschool, MESH: Base Sequence, medicine.disease_cause, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Missense mutation, MESH : Female, MESH: Animals, MESH: DNA Mutational Analysis, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genetics (clinical), Genetics, 0303 health sciences, Mutation, MESH : Cell Nucleus, MESH: X Chromosome Inactivation, MESH : Amino Acid Sequence, MESH : Infant, Phenotype, MESH: Amino Acid Substitution, MESH: Infant, Hypotonia, MESH : Sequence Homology, Amino Acid, 3. Good health, MESH: COS Cells, MESH : Phenotype, MESH : X Chromosome Inactivation, medicine.symptom, MESH : Transfection, MESH : COS Cells, MESH : Protein-Serine-Threonine Kinases, MESH: Cell Nucleus, Encephalopathy, MESH : Brain Diseases, Metabolic, Inborn, MESH : DNA Mutational Analysis, Biology, MESH: Phenotype, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, MESH : Amino Acid Substitution, MESH: Plasmids, MESH : Magnetic Resonance Imaging, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH: Electroencephalography, medicine, Atypical Rett syndrome, MESH : Electroencephalography, 030304 developmental biology, MESH: RNA, Messenger, MESH: Mutation, Missense, MESH: Humans, MESH: Transfection, MESH : Humans, MESH: Child, Preschool, medicine.disease, MESH: Cercopithecus aethiops, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH : Plasmids, MESH : Base Sequence, MESH : Animals, MESH : Cercopithecus aethiops, MESH: Female, 030217 neurology & neurosurgery, MESH : Mutation, Missense, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.
Published: 2008

49. Antagonistic effects of a Mhc class I allele on malaria-infected house sparrows

Author: Gabriele Sorci, Romain Julliard, Pierre Fédérici, Rima Zoorob, Claire Loiseau, Julien Birard, Stéphane Garnier, Parasitologie évolutive (PE), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Génétique moléculaire et intégration des fonctions cellulaires (GMIFC), Centre National de la Recherche Scientifique (CNRS), Conservation des espèces, Restauration et Suivi des Populations (CERSP), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN), Biogéosciences [UMR 6282] [Dijon] (BGS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Financial support provided by the Région Ile de France and by the Agence Nationale de la Recherche., Parasitologie évolutive ( PE ), École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique moléculaire et intégration des fonctions cellulaires ( GMIFC ), Centre National de la Recherche Scientifique ( CNRS ), Conservation des espèces, restauration et suivi des populations ( CERSP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Paris (ENS-PSL), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] (BGS), and Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Plasmodium, MESH : Molecular Sequence Data, MESH : DNA, Genes, MHC Class I, MESH: Amino Acid Sequence, co-evolution, MESH: Base Sequence, MESH : Microsatellite Repeats, 01 natural sciences, susceptibility, MESH: Sparrows, Pleiotropy, [ SDV.EE.IEO ] Life Sciences [q-bio]/Ecology, environment/Symbiosis, MESH: Animals, MESH : Malaria, Avian, Genetics, 0303 health sciences, education.field_of_study, biology, MESH : Amino Acid Sequence, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: DNA, MESH: Genetic Predisposition to Disease, MESH: Genes, MHC Class I, 3. Good health, MESH: Malaria, Avian, [ SDV.BID.EVO ] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: Haemosporida, avian malaria, Sparrows, [ SDV.MP.PAR ] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria, Avian, Molecular Sequence Data, Population, MESH: Genetics, Population, Major histocompatibility complex, 010603 evolutionary biology, MESH : Genes, MHC Class I, resistance, 03 medical and health sciences, Immune system, Avian malaria, MHC class I, medicine, Passer domesticus, Animals, Genetic Predisposition to Disease, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Amino Acid Sequence, Allele, education, Alleles, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, parasite competition, MESH: Molecular Sequence Data, Base Sequence, house sparrow, MESH: Plasmodium, MESH: Alleles, [ SDV.GEN.GA ] Life Sciences [q-bio]/Genetics/Animal genetics, DNA, Haemosporida, medicine.disease, MESH : Genetics, Population, Histocompatibility, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Genetics, Population, MESH : Plasmodium, Immunology, biology.protein, MESH : Base Sequence, MESH : Genetic Predisposition to Disease, Antagonistic pleiotropy, MESH : Sparrows, MESH : Animals, MESH : Haemosporida, MESH: Microsatellite Repeats, MESH : Alleles, Microsatellite Repeats, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: 8 pages; International audience; Genes of the Major Histocompatibility Complex (Mhc) play a fundamental role during the immune response because MHC molecules expressed on cell surface allow the recognition and presentation of antigenic peptides to T-lymphocytes. Although Mhc alleles have been found to correlate with pathogen resistance in several host-parasite systems, several studies have also reported associations between Mhc alleles and an accrued infection risk or an accelerated disease progression. The existence of these susceptibility alleles is puzzling, as the cost generated by the infection should rapidly eliminate them from the population. Here, we show that susceptibility alleles may be maintained in a population of house sparrows (Passer domesticus) if they have antagonistic effects on different malaria parasites. We found that one Mhc class I allele was associated with a 2.5-fold increase in the risk to be infected with a Plasmodium strain, but with a 6.4-fold reduction in the risk to harbour a Haemoproteus strain. We suggest that this antagonistic effect might arise because Mhc genes can alter the competitive interactions between malaria parasites within the host.
Published: 2008

50. Cloning and expression of genes involved in conidiation and surface properties of Penicillium camemberti grown in liquid and solid cultures

Author: Jean-François Cavin, Dominique Garmyn, Khadidja Boualem, Yves Waché, Patrick Gervais, A. Durand, Thomas Karbowiak, Génie des Procédés Microbiologiques et Alimentaires ( GPMA ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Microbioologie, UMR INRA 1283 Ecole Nationale Supérieure de Biologie Appliquée à la. Nutrition et à l'Alimentation, Institut National de la Recherche Agronomique ( INRA ), Laboratoire de Microbiologie, UMR INRA 1082, AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Génie des Procédés Microbiologiques et Alimentaires (GPMA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Microbioologie, and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: MESH: Sequence Analysis, DNA, MESH : Spores, Fungal, MESH : Molecular Sequence Data, Conidiation, MESH: Amino Acid Sequence, MESH: Base Sequence, Gene Expression Regulation, Fungal, Gene expression, MESH : Fungal Proteins, Cloning, Molecular, Fungal protein, MESH : Amino Acid Sequence, MESH : Sequence Alignment, General Medicine, Spores, Fungal, MESH: Mycelium, Cell biology, Weta, Penicillium camemberti, MESH: Fungal Proteins, MESH : Hydrophobicity, Hydrophobic and Hydrophilic Interactions, MESH : Mycelium, MESH: Gene Expression Regulation, Fungal, Hypha, MESH : Cloning, Molecular, Hydrophobin, Molecular Sequence Data, MESH: Sequence Alignment, Biology, Microbiology, Fungal Proteins, MESH: Spores, Fungal, MESH : Gene Expression Regulation, Fungal, MESH: Cloning, Molecular, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Molecular Biology, Gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Penicillium, MESH: Hydrophobicity, MESH: Molecular Sequence Data, Base Sequence, Mycelium, Penicillium, Sequence Analysis, DNA, MESH : Penicillium, biology.organism_classification, Culture Media, MESH: Culture Media, MESH : Base Sequence, MESH : Culture Media, Sequence Alignment, MESH : Sequence Analysis, DNA
Abstract: International audience; Based on bioinformatic data on model fungi, the rodA and wetA genes encoding, respectively, a RodA hydrophobin protein and the WetA protein involved in conidiation mechanisms, were PCR-cloned and characterized for the first time in Penicillium camemberti. These results, completed by a sequence of the brlA gene (available in GenBank), which encodes a major transcriptional regulator also involved in the conidiation mechanism, were used to compare, by qRT-PCR, the expression of the three genes in liquid and solid cultures in a synthetic medium. While expression of the brlA and wetA genes increased dramatically in both culture conditions after 4 days of growth, expression of the rodA gene increased only with conidiation and in the solid culture, and this expression was correlated with production and secretion of a RodA protein outside the hyphae, which became very hydrophobic. In liquid cultures, no production of RodA occurred in mycelia, which remained hydrophilic, and no conidiation was detected despite formation of swellings at the tips of hyphae. The absence of conidiation in liquid culture correlated with the lack of rodA gene expression, which could be regulated by the medium composition independently of brlA and wetA genes expression.
Published: 2008

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