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  • 11
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    Global mapping of the yeast genetic interaction network (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-07
    Description: A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tong, Amy Hin Yan -- Lesage, Guillaume -- Bader, Gary D -- Ding, Huiming -- Xu, Hong -- Xin, Xiaofeng -- Young, James -- Berriz, Gabriel F -- Brost, Renee L -- Chang, Michael -- Chen, YiQun -- Cheng, Xin -- Chua, Gordon -- Friesen, Helena -- Goldberg, Debra S -- Haynes, Jennifer -- Humphries, Christine -- He, Grace -- Hussein, Shamiza -- Ke, Lizhu -- Krogan, Nevan -- Li, Zhijian -- Levinson, Joshua N -- Lu, Hong -- Menard, Patrice -- Munyana, Christella -- Parsons, Ainslie B -- Ryan, Owen -- Tonikian, Raffi -- Roberts, Tania -- Sdicu, Anne-Marie -- Shapiro, Jesse -- Sheikh, Bilal -- Suter, Bernhard -- Wong, Sharyl L -- Zhang, Lan V -- Zhu, Hongwei -- Burd, Christopher G -- Munro, Sean -- Sander, Chris -- Rine, Jasper -- Greenblatt, Jack -- Peter, Matthias -- Bretscher, Anthony -- Bell, Graham -- Roth, Frederick P -- Brown, Grant W -- Andrews, Brenda -- Bussey, Howard -- Boone, Charles -- GM39066/GM/NIGMS NIH HHS/ -- GM61221/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):808-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764870" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Computational Biology ; Cystic Fibrosis/genetics ; Gene Deletion ; Genes, Essential ; *Genes, Fungal ; Genetic Diseases, Inborn/genetics ; Genotype ; Humans ; Molecular Sequence Data ; Multifactorial Inheritance ; Mutation ; Phenotype ; Polymorphism, Genetic ; Retinitis Pigmentosa/genetics ; Saccharomyces cerevisiae/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
    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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  • 12
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    Mitochondrial dysfunction in the elderly: possible role in insulin resistance (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-05-17
    Description: Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue assessed by 1H nuclear magnetic resonance (NMR) spectroscopy, and with a approximately 40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo 13C/31P NMR spectroscopy. These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004429/" 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/PMC3004429/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petersen, Kitt Falk -- Befroy, Douglas -- Dufour, Sylvie -- Dziura, James -- Ariyan, Charlotte -- Rothman, Douglas L -- DiPietro, Loretta -- Cline, Gary W -- Shulman, Gerald I -- K-23 DK-02347/DK/NIDDK NIH HHS/ -- K23 DK002734/DK/NIDDK NIH HHS/ -- K23 DK002734-04/DK/NIDDK NIH HHS/ -- M01 RR-00125/RR/NCRR NIH HHS/ -- P30 DK-45735/DK/NIDDK NIH HHS/ -- P60 AG-10469/AG/NIA NIH HHS/ -- R01 AG-09872/AG/NIA NIH HHS/ -- R01 AG023686/AG/NIA NIH HHS/ -- R01 AG023686-01A1/AG/NIA NIH HHS/ -- R01 DK-49230/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2003 May 16;300(5622):1140-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12750520" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/metabolism ; Blood Glucose/metabolism ; Body Mass Index ; Female ; Humans ; Insulin/metabolism ; *Insulin Resistance ; Liver/metabolism ; Male ; Middle Aged ; Mitochondria/*metabolism ; Mitochondrial Diseases/blood/*complications/metabolism ; Muscle, Skeletal/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Oxidation-Reduction ; Oxygen Consumption ; Phosphorylation ; Triglycerides/*metabolism
    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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  • 13
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    Control of pancreas and liver gene expression by HNF transcription factors (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-02-28
    Description: The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012624/" 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/PMC3012624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Odom, Duncan T -- Zizlsperger, Nora -- Gordon, D Benjamin -- Bell, George W -- Rinaldi, Nicola J -- Murray, Heather L -- Volkert, Tom L -- Schreiber, Jorg -- Rolfe, P Alexander -- Gifford, David K -- Fraenkel, Ernest -- Bell, Graeme I -- Young, Richard A -- N01-DK-9-2310/DK/NIDDK NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-01/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1378-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14988562" target="_blank"〉PubMed〈/a〉
    Keywords: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Carbohydrate Metabolism ; *DNA-Binding Proteins ; Diabetes Mellitus, Type 2/etiology/genetics ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome, Human ; Gluconeogenesis ; Hepatocyte Nuclear Factor 1 ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocyte Nuclear Factor 1-beta ; Hepatocyte Nuclear Factor 4 ; Hepatocyte Nuclear Factor 6 ; Hepatocytes/*metabolism ; Homeodomain Proteins/*metabolism ; Humans ; Islets of Langerhans/*metabolism ; Lipid Metabolism ; *Nuclear Proteins ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/*metabolism ; Precipitin Tests ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; Trans-Activators/*metabolism ; Transcription Factors/*metabolism ; Transcription, Genetic
    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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