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  • 1
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    FTO genotype is associated with phenotypic variability of body mass index (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-09-18
    Beschreibung: There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using approximately 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of approximately 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564953/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564953/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Jian -- Loos, Ruth J F -- Powell, Joseph E -- Medland, Sarah E -- Speliotes, Elizabeth K -- Chasman, Daniel I -- Rose, Lynda M -- Thorleifsson, Gudmar -- Steinthorsdottir, Valgerdur -- Magi, Reedik -- Waite, Lindsay -- Smith, Albert Vernon -- Yerges-Armstrong, Laura M -- Monda, Keri L -- Hadley, David -- Mahajan, Anubha -- Li, Guo -- Kapur, Karen -- Vitart, Veronique -- Huffman, Jennifer E -- Wang, Sophie R -- Palmer, Cameron -- Esko, Tonu -- Fischer, Krista -- Zhao, Jing Hua -- Demirkan, Ayse -- Isaacs, Aaron -- Feitosa, Mary F -- Luan, Jian'an -- Heard-Costa, Nancy L -- White, Charles -- Jackson, Anne U -- Preuss, Michael -- Ziegler, Andreas -- Eriksson, Joel -- Kutalik, Zoltan -- Frau, Francesca -- Nolte, Ilja M -- Van Vliet-Ostaptchouk, Jana V -- Hottenga, Jouke-Jan -- Jacobs, Kevin B -- Verweij, Niek -- Goel, Anuj -- Medina-Gomez, Carolina -- Estrada, Karol -- Bragg-Gresham, Jennifer Lynn -- Sanna, Serena -- Sidore, Carlo -- Tyrer, Jonathan -- Teumer, Alexander -- Prokopenko, Inga -- Mangino, Massimo -- Lindgren, Cecilia M -- Assimes, Themistocles L -- Shuldiner, Alan R -- Hui, Jennie -- Beilby, John P -- McArdle, Wendy L -- Hall, Per -- Haritunians, Talin -- Zgaga, Lina -- Kolcic, Ivana -- Polasek, Ozren -- Zemunik, Tatijana -- Oostra, Ben A -- Junttila, M Juhani -- Gronberg, Henrik -- Schreiber, Stefan -- Peters, Annette -- Hicks, Andrew A -- Stephens, Jonathan -- Foad, Nicola S -- Laitinen, Jaana -- Pouta, Anneli -- Kaakinen, Marika -- Willemsen, Gonneke -- Vink, Jacqueline M -- Wild, Sarah H -- Navis, Gerjan -- Asselbergs, Folkert W -- Homuth, Georg -- John, Ulrich -- Iribarren, Carlos -- Harris, Tamara -- Launer, Lenore -- Gudnason, Vilmundur -- O'Connell, Jeffrey R -- Boerwinkle, Eric -- Cadby, Gemma -- Palmer, Lyle J -- James, Alan L -- Musk, Arthur W -- Ingelsson, Erik -- Psaty, Bruce M -- Beckmann, Jacques S -- Waeber, Gerard -- Vollenweider, Peter -- Hayward, Caroline -- Wright, Alan F -- Rudan, Igor -- Groop, Leif C -- Metspalu, Andres -- Khaw, Kay Tee -- van Duijn, Cornelia M -- Borecki, Ingrid B -- Province, Michael A -- Wareham, Nicholas J -- Tardif, Jean-Claude -- Huikuri, Heikki V -- Cupples, L Adrienne -- Atwood, Larry D -- Fox, Caroline S -- Boehnke, Michael -- Collins, Francis S -- Mohlke, Karen L -- Erdmann, Jeanette -- Schunkert, Heribert -- Hengstenberg, Christian -- Stark, Klaus -- Lorentzon, Mattias -- Ohlsson, Claes -- Cusi, Daniele -- Staessen, Jan A -- Van der Klauw, Melanie M -- Pramstaller, Peter P -- Kathiresan, Sekar -- Jolley, Jennifer D -- Ripatti, Samuli -- Jarvelin, Marjo-Riitta -- de Geus, Eco J C -- Boomsma, Dorret I -- Penninx, Brenda -- Wilson, James F -- Campbell, Harry -- Chanock, Stephen J -- van der Harst, Pim -- Hamsten, Anders -- Watkins, Hugh -- Hofman, Albert -- Witteman, Jacqueline C -- Zillikens, M Carola -- Uitterlinden, Andre G -- Rivadeneira, Fernando -- Kiemeney, Lambertus A -- Vermeulen, Sita H -- Abecasis, Goncalo R -- Schlessinger, David -- Schipf, Sabine -- Stumvoll, Michael -- Tonjes, Anke -- Spector, Tim D -- North, Kari E -- Lettre, Guillaume -- McCarthy, Mark I -- Berndt, Sonja I -- Heath, Andrew C -- Madden, Pamela A F -- Nyholt, Dale R -- Montgomery, Grant W -- Martin, Nicholas G -- McKnight, Barbara -- Strachan, David P -- Hill, William G -- Snieder, Harold -- Ridker, Paul M -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- Frayling, Timothy M -- Hirschhorn, Joel N -- Goddard, Michael E -- Visscher, Peter M -- 090532/Wellcome Trust/United Kingdom -- 14136/Cancer Research UK/United Kingdom -- AA014041/AA/NIAAA NIH HHS/ -- AA07535/AA/NIAAA NIH HHS/ -- AA10248/AA/NIAAA NIH HHS/ -- AA13320/AA/NIAAA NIH HHS/ -- AA13321/AA/NIAAA NIH HHS/ -- AA13326/AA/NIAAA NIH HHS/ -- CZB/4/710/Chief Scientist Office/United Kingdom -- DA12854/DA/NIDA NIH HHS/ -- F32 AR059469/AR/NIAMS NIH HHS/ -- F32 DK079466/DK/NIDDK NIH HHS/ -- G0601261/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- GM057091/GM/NIGMS NIH HHS/ -- HHSN268201100005C/HL/NHLBI NIH HHS/ -- HHSN268201100006C/HL/NHLBI NIH HHS/ -- HHSN268201100007C/HL/NHLBI NIH HHS/ -- HHSN268201100008C/HL/NHLBI NIH HHS/ -- HHSN268201100009C/HL/NHLBI NIH HHS/ -- HHSN268201100010C/HL/NHLBI NIH HHS/ -- HHSN268201100011C/HL/NHLBI NIH HHS/ -- HHSN268201100012C/HL/NHLBI NIH HHS/ -- K05 AA017688/AA/NIAAA NIH HHS/ -- K23 DK080145/DK/NIDDK NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- N01 AG012100/AG/NIA NIH HHS/ -- N01 HC015103/HC/NHLBI NIH HHS/ -- N01 HC025195/HC/NHLBI NIH HHS/ -- N01 HC035129/HC/NHLBI NIH HHS/ -- N01 HC045133/HC/NHLBI NIH HHS/ -- N01 HC055222/HC/NHLBI NIH HHS/ -- N01 HC075150/HC/NHLBI NIH HHS/ -- N01 HC085079/HC/NHLBI NIH HHS/ -- N01 HG065403/HG/NHGRI NIH HHS/ -- N01HC85086/HL/NHLBI NIH HHS/ -- N02 HL64278/HL/NHLBI NIH HHS/ -- P30 DK063491/DK/NIDDK NIH HHS/ -- P30 DK072488/DK/NIDDK NIH HHS/ -- R01 AA007535/AA/NIAAA NIH HHS/ -- R01 AA013320/AA/NIAAA NIH HHS/ -- R01 AA013321/AA/NIAAA NIH HHS/ -- R01 AA013326/AA/NIAAA NIH HHS/ -- R01 AA014041/AA/NIAAA NIH HHS/ -- R01 AG015928/AG/NIA NIH HHS/ -- R01 AG020098/AG/NIA NIH HHS/ -- R01 AG023629/AG/NIA NIH HHS/ -- R01 AG027058/AG/NIA NIH HHS/ -- R01 DA012854/DA/NIDA NIH HHS/ -- R01 DK062370/DK/NIDDK NIH HHS/ -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK073490/DK/NIDDK NIH HHS/ -- R01 DK075681/DK/NIDDK NIH HHS/ -- R01 DK075787/DK/NIDDK NIH HHS/ -- R01 HG002651/HG/NHGRI NIH HHS/ -- R01 HL043851/HL/NHLBI NIH HHS/ -- R01 HL059367/HL/NHLBI NIH HHS/ -- R01 HL075366/HL/NHLBI NIH HHS/ -- R01 HL080295/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL087641/HL/NHLBI NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087652/HL/NHLBI NIH HHS/ -- R01 HL087676/HL/NHLBI NIH HHS/ -- R01 HL087679/HL/NHLBI NIH HHS/ -- R01 HL105756/HL/NHLBI NIH HHS/ -- R01 LM010098/LM/NLM NIH HHS/ -- R01 MH063706/MH/NIMH NIH HHS/ -- RL1 MH083268/MH/NIMH NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 HG004402/HG/NHGRI NIH HHS/ -- U01 HL054527/HL/NHLBI NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL084729/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1 RR033176/RR/NCRR NIH HHS/ -- Z01 HG000024-14/Intramural NIH HHS/ -- England -- Nature. 2012 Oct 11;490(7419):267-72. doi: 10.1038/nature11401. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982992" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Body Height/genetics ; *Body Mass Index ; Co-Repressor Proteins ; Female ; *Genetic Variation ; Genome-Wide Association Study ; Humans ; Male ; Nerve Tissue Proteins/genetics ; *Phenotype ; Polymorphism, Single Nucleotide ; Proteins/*genetics ; Repressor Proteins/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
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    Seventy-five genetic loci influencing the human red blood cell (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-12-12
    Beschreibung: Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P 〈 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623669/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623669/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van der Harst, Pim -- Zhang, Weihua -- Mateo Leach, Irene -- Rendon, Augusto -- Verweij, Niek -- Sehmi, Joban -- Paul, Dirk S -- Elling, Ulrich -- Allayee, Hooman -- Li, Xinzhong -- Radhakrishnan, Aparna -- Tan, Sian-Tsung -- Voss, Katrin -- Weichenberger, Christian X -- Albers, Cornelis A -- Al-Hussani, Abtehale -- Asselbergs, Folkert W -- Ciullo, Marina -- Danjou, Fabrice -- Dina, Christian -- Esko, Tonu -- Evans, David M -- Franke, Lude -- Gogele, Martin -- Hartiala, Jaana -- Hersch, Micha -- Holm, Hilma -- Hottenga, Jouke-Jan -- Kanoni, Stavroula -- Kleber, Marcus E -- Lagou, Vasiliki -- Langenberg, Claudia -- Lopez, Lorna M -- Lyytikainen, Leo-Pekka -- Melander, Olle -- Murgia, Federico -- Nolte, Ilja M -- O'Reilly, Paul F -- Padmanabhan, Sandosh -- Parsa, Afshin -- Pirastu, Nicola -- Porcu, Eleonora -- Portas, Laura -- Prokopenko, Inga -- Ried, Janina S -- Shin, So-Youn -- Tang, Clara S -- Teumer, Alexander -- Traglia, Michela -- Ulivi, Sheila -- Westra, Harm-Jan -- Yang, Jian -- Zhao, Jing Hua -- Anni, Franco -- Abdellaoui, Abdel -- Attwood, Antony -- Balkau, Beverley -- Bandinelli, Stefania -- Bastardot, Francois -- Benyamin, Beben -- Boehm, Bernhard O -- Cookson, William O -- Das, Debashish -- de Bakker, Paul I W -- de Boer, Rudolf A -- de Geus, Eco J C -- de Moor, Marleen H -- Dimitriou, Maria -- Domingues, Francisco S -- Doring, Angela -- Engstrom, Gunnar -- Eyjolfsson, Gudmundur Ingi -- Ferrucci, Luigi -- Fischer, Krista -- Galanello, Renzo -- Garner, Stephen F -- Genser, Bernd -- Gibson, Quince D -- Girotto, Giorgia -- Gudbjartsson, Daniel Fannar -- Harris, Sarah E -- Hartikainen, Anna-Liisa -- Hastie, Claire E -- Hedblad, Bo -- Illig, Thomas -- Jolley, Jennifer -- Kahonen, Mika -- Kema, Ido P -- Kemp, John P -- Liang, Liming -- Lloyd-Jones, Heather -- Loos, Ruth J F -- Meacham, Stuart -- Medland, Sarah E -- Meisinger, Christa -- Memari, Yasin -- Mihailov, Evelin -- Miller, Kathy -- Moffatt, Miriam F -- Nauck, Matthias -- Novatchkova, Maria -- Nutile, Teresa -- Olafsson, Isleifur -- Onundarson, Pall T -- Parracciani, Debora -- Penninx, Brenda W -- Perseu, Lucia -- Piga, Antonio -- Pistis, Giorgio -- Pouta, Anneli -- Puc, Ursula -- Raitakari, Olli -- Ring, Susan M -- Robino, Antonietta -- Ruggiero, Daniela -- Ruokonen, Aimo -- Saint-Pierre, Aude -- Sala, Cinzia -- Salumets, Andres -- Sambrook, Jennifer -- Schepers, Hein -- Schmidt, Carsten Oliver -- Sillje, Herman H W -- Sladek, Rob -- Smit, Johannes H -- Starr, John M -- Stephens, Jonathan -- Sulem, Patrick -- Tanaka, Toshiko -- Thorsteinsdottir, Unnur -- Tragante, Vinicius -- van Gilst, Wiek H -- van Pelt, L Joost -- van Veldhuisen, Dirk J -- Volker, Uwe -- Whitfield, John B -- Willemsen, Gonneke -- Winkelmann, Bernhard R -- Wirnsberger, Gerald -- Algra, Ale -- Cucca, Francesco -- d'Adamo, Adamo Pio -- Danesh, John -- Deary, Ian J -- Dominiczak, Anna F -- Elliott, Paul -- Fortina, Paolo -- Froguel, Philippe -- Gasparini, Paolo -- Greinacher, Andreas -- Hazen, Stanley L -- Jarvelin, Marjo-Riitta -- Khaw, Kay Tee -- Lehtimaki, Terho -- Maerz, Winfried -- Martin, Nicholas G -- Metspalu, Andres -- Mitchell, Braxton D -- Montgomery, Grant W -- Moore, Carmel -- Navis, Gerjan -- Pirastu, Mario -- Pramstaller, Peter P -- Ramirez-Solis, Ramiro -- Schadt, Eric -- Scott, James -- Shuldiner, Alan R -- Smith, George Davey -- Smith, J Gustav -- Snieder, Harold -- Sorice, Rossella -- Spector, Tim D -- Stefansson, Kari -- Stumvoll, Michael -- Tang, W H Wilson -- Toniolo, Daniela -- Tonjes, Anke -- Visscher, Peter M -- Vollenweider, Peter -- Wareham, Nicholas J -- Wolffenbuttel, Bruce H R -- Boomsma, Dorret I -- Beckmann, Jacques S -- Dedoussis, George V -- Deloukas, Panos -- Ferreira, Manuel A -- Sanna, Serena -- Uda, Manuela -- Hicks, Andrew A -- Penninger, Josef Martin -- Gieger, Christian -- Kooner, Jaspal S -- Ouwehand, Willem H -- Soranzo, Nicole -- Chambers, John C -- 092731/Wellcome Trust/United Kingdom -- 097117/Wellcome Trust/United Kingdom -- 14136/Cancer Research UK/United Kingdom -- CZB/4/505/Chief Scientist Office/United Kingdom -- ETM/55/Chief Scientist Office/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G1002084/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- HHSN268201100005C/HL/NHLBI NIH HHS/ -- HHSN268201100006C/HL/NHLBI NIH HHS/ -- HHSN268201100007C/HL/NHLBI NIH HHS/ -- HHSN268201100008C/HL/NHLBI NIH HHS/ -- HHSN268201100009C/HL/NHLBI NIH HHS/ -- HHSN268201100010C/HL/NHLBI NIH HHS/ -- HHSN268201100011C/HL/NHLBI NIH HHS/ -- HHSN268201100012C/HL/NHLBI NIH HHS/ -- HHSN271201100005C/DA/NIDA NIH HHS/ -- K12 RR023250/RR/NCRR NIH HHS/ -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- N01AG12109/AG/NIA NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- P20 HL113452/HL/NHLBI NIH HHS/ -- P30 DK072488/DK/NIDDK NIH HHS/ -- R01 AG018728/AG/NIA NIH HHS/ -- R01 CA165001/CA/NCI NIH HHS/ -- R01 GM053275/GM/NIGMS NIH HHS/ -- R01 HD042157/HD/NICHD NIH HHS/ -- R01 HL059367/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL087641/HL/NHLBI NIH HHS/ -- R01 HL087679/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 HL103866/HL/NHLBI NIH HHS/ -- R01 HL103931/HL/NHLBI NIH HHS/ -- R01 LM010098/LM/NLM NIH HHS/ -- R01 MH081802/MH/NIMH NIH HHS/ -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RL1 MH083268/MH/NIMH NIH HHS/ -- U01 GM074518/GM/NIGMS NIH HHS/ -- U01 HG004402/HG/NHGRI NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U24 MH068457/MH/NIMH NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1 RR025005/RR/NCRR NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- England -- Nature. 2012 Dec 20;492(7429):369-75. doi: 10.1038/nature11677. Epub 2012 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. p.van.der.harst@umcg.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222517" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Cycle/genetics ; Cytokines/metabolism ; Drosophila melanogaster/genetics ; Erythrocytes/cytology/*metabolism ; Female ; Gene Expression Regulation/genetics ; *Genetic Loci ; *Genome-Wide Association Study ; Hematopoiesis/genetics ; Hemoglobins/genetics ; Humans ; Male ; Mice ; Organ Specificity ; *Phenotype ; Polymorphism, Single Nucleotide/genetics ; RNA Interference ; Signal Transduction/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
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    An anatomically comprehensive atlas of the adult human brain transcriptome (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-09-22
    Beschreibung: Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of approximately 900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243026/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hawrylycz, Michael J -- Lein, Ed S -- Guillozet-Bongaarts, Angela L -- Shen, Elaine H -- Ng, Lydia -- Miller, Jeremy A -- van de Lagemaat, Louie N -- Smith, Kimberly A -- Ebbert, Amanda -- Riley, Zackery L -- Abajian, Chris -- Beckmann, Christian F -- Bernard, Amy -- Bertagnolli, Darren -- Boe, Andrew F -- Cartagena, Preston M -- Chakravarty, M Mallar -- Chapin, Mike -- Chong, Jimmy -- Dalley, Rachel A -- Daly, Barry David -- Dang, Chinh -- Datta, Suvro -- Dee, Nick -- Dolbeare, Tim A -- Faber, Vance -- Feng, David -- Fowler, David R -- Goldy, Jeff -- Gregor, Benjamin W -- Haradon, Zeb -- Haynor, David R -- Hohmann, John G -- Horvath, Steve -- Howard, Robert E -- Jeromin, Andreas -- Jochim, Jayson M -- Kinnunen, Marty -- Lau, Christopher -- Lazarz, Evan T -- Lee, Changkyu -- Lemon, Tracy A -- Li, Ling -- Li, Yang -- Morris, John A -- Overly, Caroline C -- Parker, Patrick D -- Parry, Sheana E -- Reding, Melissa -- Royall, Joshua J -- Schulkin, Jay -- Sequeira, Pedro Adolfo -- Slaughterbeck, Clifford R -- Smith, Simon C -- Sodt, Andy J -- Sunkin, Susan M -- Swanson, Beryl E -- Vawter, Marquis P -- Williams, Derric -- Wohnoutka, Paul -- Zielke, H Ronald -- Geschwind, Daniel H -- Hof, Patrick R -- Smith, Stephen M -- Koch, Christof -- Grant, Seth G N -- Jones, Allan R -- 066717/Wellcome Trust/United Kingdom -- 077155/Wellcome Trust/United Kingdom -- 1C76HF15069-01-00/PHS HHS/ -- 1C76HF19619-01-00/PHS HHS/ -- G0700399/Medical Research Council/United Kingdom -- G0802238/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Sep 20;489(7416):391-9. doi: 10.1038/nature11405.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Allen Institute for Brain Science, Seattle, Washington 98103, USA. mikeh@alleninstitute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22996553" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult ; *Anatomy, Artistic ; Animals ; *Atlases as Topic ; Brain/*anatomy & histology/cytology/*metabolism ; Calbindins ; Databases, Genetic ; Dopamine/metabolism ; *Gene Expression Profiling ; Health ; Hippocampus/cytology/metabolism ; Humans ; In Situ Hybridization ; Internet ; Macaca mulatta/anatomy & histology/genetics ; Male ; Mice ; Neocortex/anatomy & histology/cytology/metabolism ; Oligonucleotide Array Sequence Analysis ; Post-Synaptic Density/genetics ; RNA, Messenger/analysis/genetics ; S100 Calcium Binding Protein G/genetics ; Species Specificity ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Compensatory dendritic cell development mediated by BATF-IRF interactions (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-09-21
    Beschreibung: The AP1 transcription factor Batf3 is required for homeostatic development of CD8alpha(+) classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8alpha(+) dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-gamma. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482832/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482832/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tussiwand, Roxane -- Lee, Wan-Ling -- Murphy, Theresa L -- Mashayekhi, Mona -- KC, Wumesh -- Albring, Jorn C -- Satpathy, Ansuman T -- Rotondo, Jeffrey A -- Edelson, Brian T -- Kretzer, Nicole M -- Wu, Xiaodi -- Weiss, Leslie A -- Glasmacher, Elke -- Li, Peng -- Liao, Wei -- Behnke, Michael -- Lam, Samuel S K -- Aurthur, Cora T -- Leonard, Warren J -- Singh, Harinder -- Stallings, Christina L -- Sibley, L David -- Schreiber, Robert D -- Murphy, Kenneth M -- AI076427-02/AI/NIAID NIH HHS/ -- P30 CA91842/CA/NCI NIH HHS/ -- R01 AI036629/AI/NIAID NIH HHS/ -- R01 AI076427/AI/NIAID NIH HHS/ -- R01 CA043059/CA/NCI NIH HHS/ -- T32 AI007163/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 25;490(7421):502-7. doi: 10.1038/nature11531. Epub 2012 Sep 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22992524" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antigen Presentation ; Antigens, CD/metabolism ; Antigens, CD8/immunology/metabolism ; Basic-Leucine Zipper Transcription ; Factors/chemistry/deficiency/genetics/*metabolism ; CD4-Positive T-Lymphocytes/cytology/immunology ; CTLA-4 Antigen/metabolism ; Cell Differentiation ; Cell Line, Tumor ; Cell Lineage ; Dendritic Cells/*cytology/immunology/*metabolism ; Female ; Fibrosarcoma/immunology/metabolism/pathology ; Gene Expression Regulation ; Integrin alpha Chains/metabolism ; Interferon Regulatory Factors/deficiency/genetics/*metabolism ; Interleukin-10/metabolism ; Interleukin-12/immunology/metabolism ; Leucine Zippers ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Oncogene Protein p65(gag-jun)/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/deficiency/genetics ; T-Lymphocytes, Helper-Inducer/cytology/immunology/metabolism ; Toxoplasma/immunology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
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  • 5
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    Automated design of ligands to polypharmacological profiles (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-12-14
    Beschreibung: The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653568/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Besnard, Jeremy -- Ruda, Gian Filippo -- Setola, Vincent -- Abecassis, Keren -- Rodriguiz, Ramona M -- Huang, Xi-Ping -- Norval, Suzanne -- Sassano, Maria F -- Shin, Antony I -- Webster, Lauren A -- Simeons, Frederick R C -- Stojanovski, Laste -- Prat, Annik -- Seidah, Nabil G -- Constam, Daniel B -- Bickerton, G Richard -- Read, Kevin D -- Wetsel, William C -- Gilbert, Ian H -- Roth, Bryan L -- Hopkins, Andrew L -- 083481/Wellcome Trust/United Kingdom -- BB/FOF/PF/15/09/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J010510/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MH082441/MH/NIMH NIH HHS/ -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- WT 083481/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):215-20. doi: 10.1038/nature11691.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235874" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Automation ; Drug Delivery Systems ; *Drug Design ; Female ; *Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Pharmacological Phenomena ; Reproducibility of Results
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
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  • 6
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    An index to assess the health and benefits of the global ocean (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-08-17
    Beschreibung: The ocean plays a critical role in supporting human well-being, from providing food, livelihoods and recreational opportunities to regulating the global climate. Sustainable management aimed at maintaining the flow of a broad range of benefits from the ocean requires a comprehensive and quantitative method to measure and monitor the health of coupled human-ocean systems. We created an index comprising ten diverse public goals for a healthy coupled human-ocean system and calculated the index for every coastal country. Globally, the overall index score was 60 out of 100 (range 36-86), with developed countries generally performing better than developing countries, but with notable exceptions. Only 5% of countries scored higher than 70, whereas 32% scored lower than 50. The index provides a powerful tool to raise public awareness, direct resource management, improve policy and prioritize scientific research.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halpern, Benjamin S -- Longo, Catherine -- Hardy, Darren -- McLeod, Karen L -- Samhouri, Jameal F -- Katona, Steven K -- Kleisner, Kristin -- Lester, Sarah E -- O'Leary, Jennifer -- Ranelletti, Marla -- Rosenberg, Andrew A -- Scarborough, Courtney -- Selig, Elizabeth R -- Best, Benjamin D -- Brumbaugh, Daniel R -- Chapin, F Stuart -- Crowder, Larry B -- Daly, Kendra L -- Doney, Scott C -- Elfes, Cristiane -- Fogarty, Michael J -- Gaines, Steven D -- Jacobsen, Kelsey I -- Karrer, Leah Bunce -- Leslie, Heather M -- Neeley, Elizabeth -- Pauly, Daniel -- Polasky, Stephen -- Ris, Bud -- St Martin, Kevin -- Stone, Gregory S -- Sumaila, U Rashid -- Zeller, Dirk -- England -- Nature. 2012 Aug 30;488(7413):615-20. doi: 10.1038/nature11397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Ecological Analysis and Synthesis, 735 State St Suite 300, Santa Barbara, California 93101, USA. halpern@nceas.ucsb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22895186" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Conservation of Natural Resources/*statistics & numerical data ; *Ecosystem ; Environmental Monitoring/*methods ; Environmental Policy ; Fisheries ; Geography ; Human Activities/standards/statistics & numerical data ; *Internationality ; Marine Biology/*methods ; Oceanography/*methods ; Oceans and Seas ; Recreation ; *Seawater ; Water Pollution/analysis
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    Androgenetic haploid embryonic stem cells produce live transgenic mice (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-10-02
    Beschreibung: Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding, but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss. Recent success in establishing haploid embryonic stem (ES) cells in medaka fish and mice raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Wei -- Shuai, Ling -- Wan, Haifeng -- Dong, Mingzhu -- Wang, Meng -- Sang, Lisi -- Feng, Chunjing -- Luo, Guan-Zheng -- Li, Tianda -- Li, Xin -- Wang, Libin -- Zheng, Qin-Yuan -- Sheng, Chao -- Wu, Hua-Jun -- Liu, Zhonghua -- Liu, Lei -- Wang, Liu -- Wang, Xiu-Jie -- Zhao, Xiao-Yang -- Zhou, Qi -- England -- Nature. 2012 Oct 18;490(7420):407-11. doi: 10.1038/nature11435. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023130" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Androgens/*metabolism ; Animals ; Biomarkers/metabolism ; Blastocyst/cytology ; Cell Line ; Cell Nucleus ; Chimera/embryology/genetics ; Embryonic Stem Cells/cytology/*physiology ; Epigenesis, Genetic ; Female ; *Haploidy ; Male ; Mice ; Mice, Transgenic/embryology/genetics/*growth & development ; Models, Animal ; Models, Genetic ; Oocytes/cytology/growth & development/metabolism ; Pluripotent Stem Cells/cytology/physiology ; Sperm Injections, Intracytoplasmic ; Spermatozoa/metabolism/transplantation
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
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    Activity in motor-sensory projections reveals distributed coding in somatosensation (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-08-28
    Beschreibung: Cortical-feedback projections to primary sensory areas terminate most heavily in layer 1 (L1) of the neocortex, where they make synapses with tuft dendrites of pyramidal neurons. L1 input is thought to provide 'contextual' information, but the signals transmitted by L1 feedback remain uncharacterized. In the rodent somatosensory system, the spatially diffuse feedback projection from vibrissal motor cortex (vM1) to vibrissal somatosensory cortex (vS1, also known as the barrel cortex) may allow whisker touch to be interpreted in the context of whisker position to compute object location. When mice palpate objects with their whiskers to localize object features, whisker touch excites vS1 and later vM1 in a somatotopic manner. Here we use axonal calcium imaging to track activity in vM1--〉vS1 afferents in L1 of the barrel cortex while mice performed whisker-dependent object localization. Spatially intermingled individual axons represent whisker movements, touch and other behavioural features. In a subpopulation of axons, activity depends on object location and persists for seconds after touch. Neurons in the barrel cortex thus have information to integrate movements and touches of multiple whiskers over time, key components of object identification and navigation by active touch.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443316/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443316/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petreanu, Leopoldo -- Gutnisky, Diego A -- Huber, Daniel -- Xu, Ning-long -- O'Connor, Dan H -- Tian, Lin -- Looger, Loren -- Svoboda, Karel -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Sep 13;489(7415):299-303. doi: 10.1038/nature11321.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22922646" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Axons/metabolism ; Calcium Signaling ; Feedback, Physiological ; Male ; Mice ; Mice, Inbred C57BL ; Motor Cortex/cytology/*physiology ; Motor Neurons/metabolism ; Movement/physiology ; *Neural Pathways ; Physical Stimulation ; Somatosensory Cortex/cytology/*physiology ; Touch/*physiology ; Vibrissae/*physiology
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
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  • 9
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    Mammalian heart renewal by pre-existing cardiomyocytes (2012)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2012-12-12
    Beschreibung: Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548046/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548046/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Senyo, Samuel E -- Steinhauser, Matthew L -- Pizzimenti, Christie L -- Yang, Vicky K -- Cai, Lei -- Wang, Mei -- Wu, Ting-Di -- Guerquin-Kern, Jean-Luc -- Lechene, Claude P -- Lee, Richard T -- AG032977/AG/NIA NIH HHS/ -- AG034641/AG/NIA NIH HHS/ -- AG040019/AG/NIA NIH HHS/ -- EB001974/EB/NIBIB NIH HHS/ -- F32 HL108570/HL/NHLBI NIH HHS/ -- K08 DK090147/DK/NIDDK NIH HHS/ -- P41 EB001974/EB/NIBIB NIH HHS/ -- R01 AG040019/AG/NIA NIH HHS/ -- R21 AG034641/AG/NIA NIH HHS/ -- England -- Nature. 2013 Jan 17;493(7432):433-6. doi: 10.1038/nature11682. Epub 2012 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222518" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aging/physiology ; Animals ; Cell Cycle ; DNA/biosynthesis ; Female ; *Heart ; Homeostasis ; Isotope Labeling ; Male ; Mammals ; Mass Spectrometry ; Mice ; Myoblasts, Cardiac/cytology ; Myocardial Infarction/genetics/metabolism/pathology ; Myocardium/*cytology/metabolism/pathology ; Myocytes, Cardiac/*cytology/metabolism ; Polyploidy ; *Regeneration
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von Nature Publishing Group (NPG)
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  • 10
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    Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited ISG15 deficiency (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publikationsdatum: 2012-08-04
    Beschreibung: ISG15 is an interferon (IFN)-alpha/beta-inducible, ubiquitin-like intracellular protein. Its conjugation to various proteins (ISGylation) contributes to antiviral immunity in mice. Here, we describe human patients with inherited ISG15 deficiency and mycobacterial, but not viral, diseases. The lack of intracellular ISG15 production and protein ISGylation was not associated with cellular susceptibility to any viruses that we tested, consistent with the lack of viral diseases in these patients. By contrast, the lack of mycobacterium-induced ISG15 secretion by leukocytes-granulocyte, in particular-reduced the production of IFN-gamma by lymphocytes, including natural killer cells, probably accounting for the enhanced susceptibility to mycobacterial disease. This experiment of nature shows that human ISGylation is largely redundant for antiviral immunity, but that ISG15 plays an essential role as an IFN-gamma-inducing secreted molecule for optimal antimycobacterial immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507439/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bogunovic, Dusan -- Byun, Minji -- Durfee, Larissa A -- Abhyankar, Avinash -- Sanal, Ozden -- Mansouri, Davood -- Salem, Sandra -- Radovanovic, Irena -- Grant, Audrey V -- Adimi, Parisa -- Mansouri, Nahal -- Okada, Satoshi -- Bryant, Vanessa L -- Kong, Xiao-Fei -- Kreins, Alexandra -- Velez, Marcela Moncada -- Boisson, Bertrand -- Khalilzadeh, Soheila -- Ozcelik, Ugur -- Darazam, Ilad Alavi -- Schoggins, John W -- Rice, Charles M -- Al-Muhsen, Saleh -- Behr, Marcel -- Vogt, Guillaume -- Puel, Anne -- Bustamante, Jacinta -- Gros, Philippe -- Huibregtse, Jon M -- Abel, Laurent -- Boisson-Dupuis, Stephanie -- Casanova, Jean-Laurent -- 1R37AI095983-01/AI/NIAID NIH HHS/ -- 5R01AI035237-15/AI/NIAID NIH HHS/ -- 8UL1TR000043/TR/NCATS NIH HHS/ -- AI096090/AI/NIAID NIH HHS/ -- CA072943/CA/NCI NIH HHS/ -- R01 AI035237/AI/NIAID NIH HHS/ -- R01 AI091707/AI/NIAID NIH HHS/ -- R01 AI096090/AI/NIAID NIH HHS/ -- R01 CA072943/CA/NCI NIH HHS/ -- R37 AI095983/AI/NIAID NIH HHS/ -- UL1 TR000043/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 28;337(6102):1684-8. Epub 2012 Aug 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859821" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antibodies, Viral/blood ; Cytokines/genetics/*immunology ; Female ; Granulocytes/immunology ; Humans ; Immunity ; Interferon-gamma/*immunology ; Interleukin-12/immunology ; Killer Cells, Natural/immunology ; Male ; Mice ; Mycobacterium Infections/blood/genetics/*immunology ; Pedigree ; T-Lymphocytes/immunology ; Ubiquitins/genetics/*immunology ; Virus Diseases/blood/*immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Publiziert von American Association for the Advancement of Science (AAAS)
    Standort Signatur Erwartet Verfügbarkeit
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