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  • Female  (91)
  • Amino Acid Sequence
  • Life Sciences (General)
  • Meteorology and Climatology
  • 2005-2009  (160)
  • 2000-2004
  • 1950-1954
  • 2009  (160)
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  • 2005-2009  (160)
  • 2000-2004
  • 1950-1954
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  • 1
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    The genome sequence of taurine cattle: a window to ruminant biology and evolution (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-25
    Description: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200/" 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/PMC2943200/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bovine Genome Sequencing and Analysis Consortium -- Elsik, Christine G -- Tellam, Ross L -- Worley, Kim C -- Gibbs, Richard A -- Muzny, Donna M -- Weinstock, George M -- Adelson, David L -- Eichler, Evan E -- Elnitski, Laura -- Guigo, Roderic -- Hamernik, Debora L -- Kappes, Steve M -- Lewin, Harris A -- Lynn, David J -- Nicholas, Frank W -- Reymond, Alexandre -- Rijnkels, Monique -- Skow, Loren C -- Zdobnov, Evgeny M -- Schook, Lawrence -- Womack, James -- Alioto, Tyler -- Antonarakis, Stylianos E -- Astashyn, Alex -- Chapple, Charles E -- Chen, Hsiu-Chuan -- Chrast, Jacqueline -- Camara, Francisco -- Ermolaeva, Olga -- Henrichsen, Charlotte N -- Hlavina, Wratko -- Kapustin, Yuri -- Kiryutin, Boris -- Kitts, Paul -- Kokocinski, Felix -- Landrum, Melissa -- Maglott, Donna -- Pruitt, Kim -- Sapojnikov, Victor -- Searle, Stephen M -- Solovyev, Victor -- Souvorov, Alexandre -- Ucla, Catherine -- Wyss, Carine -- Anzola, Juan M -- Gerlach, Daniel -- Elhaik, Eran -- Graur, Dan -- Reese, Justin T -- Edgar, Robert C -- McEwan, John C -- Payne, Gemma M -- Raison, Joy M -- Junier, Thomas -- Kriventseva, Evgenia V -- Eyras, Eduardo -- Plass, Mireya -- Donthu, Ravikiran -- Larkin, Denis M -- Reecy, James -- Yang, Mary Q -- Chen, Lin -- Cheng, Ze -- Chitko-McKown, Carol G -- Liu, George E -- Matukumalli, Lakshmi K -- Song, Jiuzhou -- Zhu, Bin -- Bradley, Daniel G -- Brinkman, Fiona S L -- Lau, Lilian P L -- Whiteside, Matthew D -- Walker, Angela -- Wheeler, Thomas T -- Casey, Theresa -- German, J Bruce -- Lemay, Danielle G -- Maqbool, Nauman J -- Molenaar, Adrian J -- Seo, Seongwon -- Stothard, Paul -- Baldwin, Cynthia L -- Baxter, Rebecca -- Brinkmeyer-Langford, Candice L -- Brown, Wendy C -- Childers, Christopher P -- Connelley, Timothy -- Ellis, Shirley A -- Fritz, Krista -- Glass, Elizabeth J -- Herzig, Carolyn T A -- Iivanainen, Antti -- Lahmers, Kevin K -- Bennett, Anna K -- Dickens, C Michael -- Gilbert, James G R -- Hagen, Darren E -- Salih, Hanni -- Aerts, Jan -- Caetano, Alexandre R -- Dalrymple, Brian -- Garcia, Jose Fernando -- Gill, Clare A -- Hiendleder, Stefan G -- Memili, Erdogan -- Spurlock, Diane -- Williams, John L -- Alexander, Lee -- Brownstein, Michael J -- Guan, Leluo -- Holt, Robert A -- Jones, Steven J M -- Marra, Marco A -- Moore, Richard -- Moore, Stephen S -- Roberts, Andy -- Taniguchi, Masaaki -- Waterman, Richard C -- Chacko, Joseph -- Chandrabose, Mimi M -- Cree, Andy -- Dao, Marvin Diep -- Dinh, Huyen H -- Gabisi, Ramatu Ayiesha -- Hines, Sandra -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Kovar, Christie L -- Lewis, Lora R -- Liu, Yih-Shin -- Lopez, John -- Morgan, Margaret B -- Nguyen, Ngoc Bich -- Okwuonu, Geoffrey O -- Ruiz, San Juana -- Santibanez, Jireh -- Wright, Rita A -- Buhay, Christian -- Ding, Yan -- Dugan-Rocha, Shannon -- Herdandez, Judith -- Holder, Michael -- Sabo, Aniko -- Egan, Amy -- Goodell, Jason -- Wilczek-Boney, Katarzyna -- Fowler, Gerald R -- Hitchens, Matthew Edward -- Lozado, Ryan J -- Moen, Charles -- Steffen, David -- Warren, James T -- Zhang, Jingkun -- Chiu, Readman -- Schein, Jacqueline E -- Durbin, K James -- Havlak, Paul -- Jiang, Huaiyang -- Liu, Yue -- Qin, Xiang -- Ren, Yanru -- Shen, Yufeng -- Song, Henry -- Bell, Stephanie Nicole -- Davis, Clay -- Johnson, Angela Jolivet -- Lee, Sandra -- Nazareth, Lynne V -- Patel, Bella Mayurkumar -- Pu, Ling-Ling -- Vattathil, Selina -- Williams, Rex Lee Jr -- Curry, Stacey -- Hamilton, Cerissa -- Sodergren, Erica -- Wheeler, David A -- Barris, Wes -- Bennett, Gary L -- Eggen, Andre -- Green, Ronnie D -- Harhay, Gregory P -- Hobbs, Matthew -- Jann, Oliver -- Keele, John W -- Kent, Matthew P -- Lien, Sigbjorn -- McKay, Stephanie D -- McWilliam, Sean -- Ratnakumar, Abhirami -- Schnabel, Robert D -- Smith, Timothy -- Snelling, Warren M -- Sonstegard, Tad S -- Stone, Roger T -- Sugimoto, Yoshikazu -- Takasuga, Akiko -- Taylor, Jeremy F -- Van Tassell, Curtis P -- Macneil, Michael D -- Abatepaulo, Antonio R R -- Abbey, Colette A -- Ahola, Virpi -- Almeida, Iassudara G -- Amadio, Ariel F -- Anatriello, Elen -- Bahadue, Suria M -- Biase, Fernando H -- Boldt, Clayton R -- Carroll, Jeffery A -- Carvalho, Wanessa A -- Cervelatti, Eliane P -- Chacko, Elsa -- Chapin, Jennifer E -- Cheng, Ye -- Choi, Jungwoo -- Colley, Adam J -- de Campos, Tatiana A -- De Donato, Marcos -- Santos, Isabel K F de Miranda -- de Oliveira, Carlo J F -- Deobald, Heather -- Devinoy, Eve -- Donohue, Kaitlin E -- Dovc, Peter -- Eberlein, Annett -- Fitzsimmons, Carolyn J -- Franzin, Alessandra M -- Garcia, Gustavo R -- Genini, Sem -- Gladney, Cody J -- Grant, Jason R -- Greaser, Marion L -- Green, Jonathan A -- Hadsell, Darryl L -- Hakimov, Hatam A -- Halgren, Rob -- Harrow, Jennifer L -- Hart, Elizabeth A -- Hastings, Nicola -- Hernandez, Marta -- Hu, Zhi-Liang -- Ingham, Aaron -- Iso-Touru, Terhi -- Jamis, Catherine -- Jensen, Kirsty -- Kapetis, Dimos -- Kerr, Tovah -- Khalil, Sari S -- Khatib, Hasan -- Kolbehdari, Davood -- Kumar, Charu G -- Kumar, Dinesh -- Leach, Richard -- Lee, Justin C-M -- Li, Changxi -- Logan, Krystin M -- Malinverni, Roberto -- Marques, Elisa -- Martin, William F -- Martins, Natalia F -- Maruyama, Sandra R -- Mazza, Raffaele -- McLean, Kim L -- Medrano, Juan F -- Moreno, Barbara T -- More, Daniela D -- Muntean, Carl T -- Nandakumar, Hari P -- Nogueira, Marcelo F G -- Olsaker, Ingrid -- Pant, Sameer D -- Panzitta, Francesca -- Pastor, Rosemeire C P -- Poli, Mario A -- Poslusny, Nathan -- Rachagani, Satyanarayana -- Ranganathan, Shoba -- Razpet, Andrej -- Riggs, Penny K -- Rincon, Gonzalo -- Rodriguez-Osorio, Nelida -- Rodriguez-Zas, Sandra L -- Romero, Natasha E -- Rosenwald, Anne -- Sando, Lillian -- Schmutz, Sheila M -- Shen, Libing -- Sherman, Laura -- Southey, Bruce R -- Lutzow, Ylva Strandberg -- Sweedler, Jonathan V -- Tammen, Imke -- Telugu, Bhanu Prakash V L -- Urbanski, Jennifer M -- Utsunomiya, Yuri T -- Verschoor, Chris P -- Waardenberg, Ashley J -- Wang, Zhiquan -- Ward, Robert -- Weikard, Rosemarie -- Welsh, Thomas H Jr -- White, Stephen N -- Wilming, Laurens G -- Wunderlich, Kris R -- Yang, Jianqi -- Zhao, Feng-Qi -- 062023/Wellcome Trust/United Kingdom -- 077198/Wellcome Trust/United Kingdom -- BBS/B/13438/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/13446/Biotechnology and Biological Sciences Research Council/United Kingdom -- P30 DA018310/DA/NIDA NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273-04/HG/NHGRI NIH HHS/ -- U54 HG003273-04S1/HG/NHGRI NIH HHS/ -- U54 HG003273-05/HG/NHGRI NIH HHS/ -- U54 HG003273-05S1/HG/NHGRI NIH HHS/ -- U54 HG003273-05S2/HG/NHGRI NIH HHS/ -- U54 HG003273-06/HG/NHGRI NIH HHS/ -- U54 HG003273-06S1/HG/NHGRI NIH HHS/ -- U54 HG003273-06S2/HG/NHGRI NIH HHS/ -- U54 HG003273-07/HG/NHGRI NIH HHS/ -- U54 HG003273-08/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):522-8. doi: 10.1126/science.1169588.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390049" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Animals ; Animals, Domestic ; *Biological Evolution ; Cattle ; Evolution, Molecular ; Female ; Genetic Variation ; *Genome ; Humans ; Male ; MicroRNAs/genetics ; Molecular Sequence Data ; Proteins/genetics ; Sequence Analysis, DNA ; Species Specificity ; Synteny
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-04-25
    Description: The imprints of domestication and breed development on the genomes of livestock likely differ from those of companion animals. A deep draft sequence assembly of shotgun reads from a single Hereford female and comparative sequences sampled from six additional breeds were used to develop probes to interrogate 37,470 single-nucleotide polymorphisms (SNPs) in 497 cattle from 19 geographically and biologically diverse breeds. These data show that cattle have undergone a rapid recent decrease in effective population size from a very large ancestral population, possibly due to bottlenecks associated with domestication, selection, and breed formation. Domestication and artificial selection appear to have left detectable signatures of selection within the cattle genome, yet the current levels of diversity within breeds are at least as great as exists within humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735092/" 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/PMC2735092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bovine HapMap Consortium -- Gibbs, Richard A -- Taylor, Jeremy F -- Van Tassell, Curtis P -- Barendse, William -- Eversole, Kellye A -- Gill, Clare A -- Green, Ronnie D -- Hamernik, Debora L -- Kappes, Steven M -- Lien, Sigbjorn -- Matukumalli, Lakshmi K -- McEwan, John C -- Nazareth, Lynne V -- Schnabel, Robert D -- Weinstock, George M -- Wheeler, David A -- Ajmone-Marsan, Paolo -- Boettcher, Paul J -- Caetano, Alexandre R -- Garcia, Jose Fernando -- Hanotte, Olivier -- Mariani, Paola -- Skow, Loren C -- Sonstegard, Tad S -- Williams, John L -- Diallo, Boubacar -- Hailemariam, Lemecha -- Martinez, Mario L -- Morris, Chris A -- Silva, Luiz O C -- Spelman, Richard J -- Mulatu, Woudyalew -- Zhao, Keyan -- Abbey, Colette A -- Agaba, Morris -- Araujo, Flabio R -- Bunch, Rowan J -- Burton, James -- Gorni, Chiara -- Olivier, Hanotte -- Harrison, Blair E -- Luff, Bill -- Machado, Marco A -- Mwakaya, Joel -- Plastow, Graham -- Sim, Warren -- Smith, Timothy -- Thomas, Merle B -- Valentini, Alessio -- Williams, Paul -- Womack, James -- Woolliams, John A -- Liu, Yue -- Qin, Xiang -- Worley, Kim C -- Gao, Chuan -- Jiang, Huaiyang -- Moore, Stephen S -- Ren, Yanru -- Song, Xing-Zhi -- Bustamante, Carlos D -- Hernandez, Ryan D -- Muzny, Donna M -- Patil, Shobha -- San Lucas, Anthony -- Fu, Qing -- Kent, Matthew P -- Vega, Richard -- Matukumalli, Aruna -- McWilliam, Sean -- Sclep, Gert -- Bryc, Katarzyna -- Choi, Jungwoo -- Gao, Hong -- Grefenstette, John J -- Murdoch, Brenda -- Stella, Alessandra -- Villa-Angulo, Rafael -- Wright, Mark -- Aerts, Jan -- Jann, Oliver -- Negrini, Riccardo -- Goddard, Mike E -- Hayes, Ben J -- Bradley, Daniel G -- Barbosa da Silva, Marcos -- Lau, Lilian P L -- Liu, George E -- Lynn, David J -- Panzitta, Francesca -- Dodds, Ken G -- R01 GM083606/GM/NIGMS NIH HHS/ -- R01 GM083606-02/GM/NIGMS NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2009 Apr 24;324(5926):528-32. doi: 10.1126/science.1167936.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19390050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breeding ; Cattle/*genetics ; Female ; Gene Frequency ; *Genetic Variation ; *Genome ; Male ; Molecular Sequence Data ; Mutation ; *Polymorphism, Single Nucleotide ; Population Density
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Ribosomal protein S6 kinase 1 signaling regulates mammalian life span (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-10-03
    Description: Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Selman, Colin -- Tullet, Jennifer M A -- Wieser, Daniela -- Irvine, Elaine -- Lingard, Steven J -- Choudhury, Agharul I -- Claret, Marc -- Al-Qassab, Hind -- Carmignac, Danielle -- Ramadani, Faruk -- Woods, Angela -- Robinson, Iain C A -- Schuster, Eugene -- Batterham, Rachel L -- Kozma, Sara C -- Thomas, George -- Carling, David -- Okkenhaug, Klaus -- Thornton, Janet M -- Partridge, Linda -- Gems, David -- Withers, Dominic J -- BBS/E/B/0000C236/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/E/B/0000M979/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0800339/Medical Research Council/United Kingdom -- G108/551/Medical Research Council/United Kingdom -- MC_U117531708/Medical Research Council/United Kingdom -- MC_U120027537/Medical Research Council/United Kingdom -- MC_U120097114/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2009 Oct 2;326(5949):140-4. doi: 10.1126/science.1177221.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19797661" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; Adipose Tissue, White/metabolism ; Aging/*physiology ; Animals ; Bone Density ; Caloric Restriction ; Female ; Gene Deletion ; Gene Expression ; Gene Expression Regulation ; Insulin/metabolism ; Liver/metabolism ; Longevity/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; Muscle, Skeletal/metabolism ; Protein Kinases/metabolism ; Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism ; *Signal Transduction ; T-Lymphocyte Subsets/immunology ; TOR Serine-Threonine Kinases ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Genetic variation in IL28B and spontaneous clearance of hepatitis C virus (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-09-18
    Description: Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance. Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172006/" 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/PMC3172006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, David L -- Thio, Chloe L -- Martin, Maureen P -- Qi, Ying -- Ge, Dongliang -- O'Huigin, Colm -- Kidd, Judith -- Kidd, Kenneth -- Khakoo, Salim I -- Alexander, Graeme -- Goedert, James J -- Kirk, Gregory D -- Donfield, Sharyne M -- Rosen, Hugo R -- Tobler, Leslie H -- Busch, Michael P -- McHutchison, John G -- Goldstein, David B -- Carrington, Mary -- HHSN261200800001E/CO/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 DA004334/DA/NIDA NIH HHS/ -- R01DA004334/DA/NIDA NIH HHS/ -- R01DA013324/DA/NIDA NIH HHS/ -- R01DK60590/DK/NIDDK NIH HHS/ -- R01HD41224/HD/NICHD NIH HHS/ -- R01HL076902/HL/NHLBI NIH HHS/ -- R56 DA004334/DA/NIDA NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2009 Oct 8;461(7265):798-801. doi: 10.1038/nature08463.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University, Division of Infectious Diseases, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759533" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Africa/ethnology ; Europe/ethnology ; Female ; Gene Frequency ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Genotype ; Hepacivirus/drug effects/*immunology/physiology ; Hepatitis C/drug therapy/*genetics/*immunology/virology ; Humans ; Interleukins/*genetics/*immunology ; Male ; Polymorphism, Single Nucleotide/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    Complex landscapes of somatic rearrangement in human breast cancer genomes (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-25
    Description: Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398135/" 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/PMC3398135/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, Philip J -- McBride, David J -- Lin, Meng-Lay -- Varela, Ignacio -- Pleasance, Erin D -- Simpson, Jared T -- Stebbings, Lucy A -- Leroy, Catherine -- Edkins, Sarah -- Mudie, Laura J -- Greenman, Chris D -- Jia, Mingming -- Latimer, Calli -- Teague, Jon W -- Lau, King Wai -- Burton, John -- Quail, Michael A -- Swerdlow, Harold -- Churcher, Carol -- Natrajan, Rachael -- Sieuwerts, Anieta M -- Martens, John W M -- Silver, Daniel P -- Langerod, Anita -- Russnes, Hege E G -- Foekens, John A -- Reis-Filho, Jorge S -- van 't Veer, Laura -- Richardson, Andrea L -- Borresen-Dale, Anne-Lise -- Campbell, Peter J -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- CA089393/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 24;462(7276):1005-10. doi: 10.1038/nature08645.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033038" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/*genetics ; Cell Line, Tumor ; Cells, Cultured ; *Chromosome Aberrations ; DNA Breaks ; Female ; Gene Rearrangement/*genetics ; Genome, Human/*genetics ; Genomic Library ; Humans ; Sequence Analysis, DNA
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Solution nuclear magnetic resonance structure of membrane-integral diacylglycerol kinase (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-06-27
    Description: Escherichia coli diacylglycerol kinase (DAGK) represents a family of integral membrane enzymes that is unrelated to all other phosphotransferases. We have determined the three-dimensional structure of the DAGK homotrimer with the use of solution nuclear magnetic resonance. The third transmembrane helix from each subunit is domain-swapped with the first and second transmembrane segments from an adjacent subunit. Each of DAGK's three active sites resembles a portico. The cornice of the portico appears to be the determinant of DAGK's lipid substrate specificity and overhangs the site of phosphoryl transfer near the water-membrane interface. Mutations to cysteine that caused severe misfolding were located in or near the active site, indicating a high degree of overlap between sites responsible for folding and for catalysis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764269/" 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/PMC2764269/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Horn, Wade D -- Kim, Hak-Jun -- Ellis, Charles D -- Hadziselimovic, Arina -- Sulistijo, Endah S -- Karra, Murthy D -- Tian, Changlin -- Sonnichsen, Frank D -- Sanders, Charles R -- R01 GM047485/GM/NIGMS NIH HHS/ -- R01 GM047485-17/GM/NIGMS NIH HHS/ -- R01 GM47485/GM/NIGMS NIH HHS/ -- T32 NS007491/NS/NINDS NIH HHS/ -- T32 NS007491-09/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jun 26;324(5935):1726-9. doi: 10.1126/science.1171716.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19556511" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Biocatalysis ; Catalytic Domain ; Cell Membrane/enzymology ; Diacylglycerol Kinase/*chemistry/metabolism ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 7
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    Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120 (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-08
    Description: The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862588/" 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/PMC2862588/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Lei -- Kwon, Young Do -- Zhou, Tongqing -- Wu, Xueling -- O'Dell, Sijy -- Cavacini, Lisa -- Hessell, Ann J -- Pancera, Marie -- Tang, Min -- Xu, Ling -- Yang, Zhi-Yong -- Zhang, Mei-Yun -- Arthos, James -- Burton, Dennis R -- Dimitrov, Dimiter S -- Nabel, Gary J -- Posner, Marshall R -- Sodroski, Joseph -- Wyatt, Richard -- Mascola, John R -- Kwong, Peter D -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2009 Nov 20;326(5956):1123-7. doi: 10.1126/science.1175868.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965434" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antibodies, Neutralizing/chemistry/*immunology/metabolism ; Antigens, CD4/chemistry/*metabolism ; Binding Sites ; Binding Sites, Antibody ; Crystallography, X-Ray ; Epitopes ; HIV Antibodies/*chemistry/*immunology/metabolism ; HIV Envelope Protein gp120/*chemistry/*immunology/metabolism ; Hiv-1 ; Humans ; Hydrophobic and Hydrophilic Interactions ; *Immune Evasion ; Models, Molecular ; Molecular Sequence Data ; Peptide Fragments/chemistry/immunology/metabolism ; Protein Conformation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    The sequence and de novo assembly of the giant panda genome (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-17
    Description: Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951497/" 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/PMC3951497/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ruiqiang -- Fan, Wei -- Tian, Geng -- Zhu, Hongmei -- He, Lin -- Cai, Jing -- Huang, Quanfei -- Cai, Qingle -- Li, Bo -- Bai, Yinqi -- Zhang, Zhihe -- Zhang, Yaping -- Wang, Wen -- Li, Jun -- Wei, Fuwen -- Li, Heng -- Jian, Min -- Li, Jianwen -- Zhang, Zhaolei -- Nielsen, Rasmus -- Li, Dawei -- Gu, Wanjun -- Yang, Zhentao -- Xuan, Zhaoling -- Ryder, Oliver A -- Leung, Frederick Chi-Ching -- Zhou, Yan -- Cao, Jianjun -- Sun, Xiao -- Fu, Yonggui -- Fang, Xiaodong -- Guo, Xiaosen -- Wang, Bo -- Hou, Rong -- Shen, Fujun -- Mu, Bo -- Ni, Peixiang -- Lin, Runmao -- Qian, Wubin -- Wang, Guodong -- Yu, Chang -- Nie, Wenhui -- Wang, Jinhuan -- Wu, Zhigang -- Liang, Huiqing -- Min, Jiumeng -- Wu, Qi -- Cheng, Shifeng -- Ruan, Jue -- Wang, Mingwei -- Shi, Zhongbin -- Wen, Ming -- Liu, Binghang -- Ren, Xiaoli -- Zheng, Huisong -- Dong, Dong -- Cook, Kathleen -- Shan, Gao -- Zhang, Hao -- Kosiol, Carolin -- Xie, Xueying -- Lu, Zuhong -- Zheng, Hancheng -- Li, Yingrui -- Steiner, Cynthia C -- Lam, Tommy Tsan-Yuk -- Lin, Siyuan -- Zhang, Qinghui -- Li, Guoqing -- Tian, Jing -- Gong, Timing -- Liu, Hongde -- Zhang, Dejin -- Fang, Lin -- Ye, Chen -- Zhang, Juanbin -- Hu, Wenbo -- Xu, Anlong -- Ren, Yuanyuan -- Zhang, Guojie -- Bruford, Michael W -- Li, Qibin -- Ma, Lijia -- Guo, Yiran -- An, Na -- Hu, Yujie -- Zheng, Yang -- Shi, Yongyong -- Li, Zhiqiang -- Liu, Qing -- Chen, Yanling -- Zhao, Jing -- Qu, Ning -- Zhao, Shancen -- Tian, Feng -- Wang, Xiaoling -- Wang, Haiyin -- Xu, Lizhi -- Liu, Xiao -- Vinar, Tomas -- Wang, Yajun -- Lam, Tak-Wah -- Yiu, Siu-Ming -- Liu, Shiping -- Zhang, Hemin -- Li, Desheng -- Huang, Yan -- Wang, Xia -- Yang, Guohua -- Jiang, Zhi -- Wang, Junyi -- Qin, Nan -- Li, Li -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Wong, Gane Ka-Shu -- Olson, Maynard -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):311-7. doi: 10.1038/nature08696. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010809" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; China ; Conserved Sequence/genetics ; Contig Mapping ; Diet/veterinary ; Dogs ; Evolution, Molecular ; Female ; Fertility/genetics/physiology ; Genome/*genetics ; *Genomics ; Heterozygote ; Humans ; Multigene Family/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Synteny/genetics ; Ursidae/classification/*genetics/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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    Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-12-17
    Description: The majority of excitatory synapses in the mammalian CNS (central nervous system) are formed on dendritic spines, and spine morphology and distribution are critical for synaptic transmission, synaptic integration and plasticity. Here, we show that a secreted semaphorin, Sema3F, is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (Npn-2, also known as Nrp2) and plexin A3 (PlexA3, also known as Plxna3), exhibit increased dentate gyrus (DG) granule cell (GC) and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn-2(-/-) brain slices cortical layer V and DG GCs exhibit increased mEPSC (miniature excitatory postsynaptic current) frequency. In contrast, a distinct Sema3A-Npn-1/PlexA4 signalling cascade controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. These disparate effects of secreted semaphorins are reflected in the restricted dendritic localization of Npn-2 to apical dendrites and of Npn-1 (also known as Nrp1) to all dendrites of cortical pyramidal neurons. Therefore, Sema3F signalling controls spine distribution along select dendritic processes, and distinct secreted semaphorin signalling events orchestrate CNS connectivity through the differential control of spine morphogenesis, synapse formation, and the elaboration of dendritic morphology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842559/" 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/PMC2842559/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tran, Tracy S -- Rubio, Maria E -- Clem, Roger L -- Johnson, Dontais -- Case, Lauren -- Tessier-Lavigne, Marc -- Huganir, Richard L -- Ginty, David D -- Kolodkin, Alex L -- F32 NS051003/NS/NINDS NIH HHS/ -- P50 MH06883/MH/NIMH NIH HHS/ -- R01 DC-006881/DC/NIDCD NIH HHS/ -- R01 MH059199/MH/NIMH NIH HHS/ -- R01 MH059199-07/MH/NIMH NIH HHS/ -- R01 MH059199-08/MH/NIMH NIH HHS/ -- R01 MH059199-09/MH/NIMH NIH HHS/ -- R01 MH059199-10/MH/NIMH NIH HHS/ -- R01 MH59199/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Dec 24;462(7276):1065-9. doi: 10.1038/nature08628. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010807" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/cytology/drug effects/*growth & ; development/*metabolism/ultrastructure ; Female ; Gene Expression Regulation, Developmental ; Male ; Mice ; Mice, Knockout ; Neuropilin-1/metabolism ; Neuropilin-2/metabolism ; Pyramidal Cells/*cytology/drug effects/*growth & development/ultrastructure ; Recombinant Proteins/pharmacology ; Semaphorins/genetics/*metabolism/pharmacology ; Signal Transduction ; Synapses/drug effects/*physiology/ultrastructure
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    XIAP discriminates between type I and type II FAS-induced apoptosis (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-07-25
    Description: FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956120/" 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/PMC2956120/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jost, Philipp J -- Grabow, Stephanie -- Gray, Daniel -- McKenzie, Mark D -- Nachbur, Ueli -- Huang, David C S -- Bouillet, Philippe -- Thomas, Helen E -- Borner, Christoph -- Silke, John -- Strasser, Andreas -- Kaufmann, Thomas -- CA 43540/CA/NCI NIH HHS/ -- CA 80188/CA/NCI NIH HHS/ -- R01 CA043540/CA/NCI NIH HHS/ -- R01 CA043540-09/CA/NCI NIH HHS/ -- R01 CA043540-22/CA/NCI NIH HHS/ -- R01 CA080188-01/CA/NCI NIH HHS/ -- R01 CA080188-08/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1035-9. doi: 10.1038/nature08229. Epub 2009 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626005" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/antagonists & inhibitors/immunology/*metabolism ; *Apoptosis ; BH3 Interacting Domain Death Agonist Protein/deficiency/genetics ; Biomimetic Materials/pharmacology ; Caspase Inhibitors ; Enzyme Activation ; Fas Ligand Protein/metabolism ; Female ; Hepatitis/metabolism/pathology ; Hepatocytes/cytology/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; Thymus Gland/cytology/drug effects ; X-Linked Inhibitor of Apoptosis Protein/antagonists & ; inhibitors/deficiency/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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