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  • Humans  (3)
  • Aquatic Organisms/*physiology  (1)
  • American Association for the Advancement of Science (AAAS)  (4)
  • 1
    Publication Date: 2001-11-27
    Description: With the draft sequence of the human genome available, there is a need to better define gene function in the context of systems biology. We studied 239 cardiovascular and renal phenotypes in 113 male rats derived from an F2 intercross and mapped 81 of these traits onto the genome. Aggregates of traits were identified on chromosomes 1, 2, 7, and 18. Systems biology was assessed by examining patterns of correlations ("physiological profiles") that can be used for gene hunting, mechanism-based physiological studies, and, with comparative genomics, translating these data to the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stoll, M -- Cowley, A W Jr -- Tonellato, P J -- Greene, A S -- Kaldunski, M L -- Roman, R J -- Dumas, P -- Schork, N J -- Wang, Z -- Jacob, H J -- 1P50-HL-54998/HL/NHLBI NIH HHS/ -- R01 HL064541/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1723-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Bioinformatics Research Center, and, Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226-0509, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721057" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Pressure/drug effects/genetics ; *Cardiovascular Physiological Phenomena/drug effects ; Chromosome Mapping/*methods ; Chromosomes/genetics ; Crosses, Genetic ; Female ; Genomics/*methods ; Humans ; Kidney/physiology ; Lod Score ; Male ; Nitric Oxide Synthase/genetics ; Norepinephrine/pharmacology ; Phenotype ; Quantitative Trait, Heritable ; Rats ; Vasodilation/genetics
    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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  • 2
    Publication Date: 2013-02-09
    Description: Mutations in IDH1 and IDH2, the genes coding for isocitrate dehydrogenases 1 and 2, are common in several human cancers, including leukemias, and result in overproduction of the (R)-enantiomer of 2-hydroxyglutarate [(R)-2HG]. Elucidation of the role of IDH mutations and (R)-2HG in leukemogenesis has been hampered by a lack of appropriate cell-based models. Here, we show that a canonical IDH1 mutant, IDH1 R132H, promotes cytokine independence and blocks differentiation in hematopoietic cells. These effects can be recapitulated by (R)-2HG, but not (S)-2HG, despite the fact that (S)-2HG more potently inhibits enzymes, such as the 5'-methylcytosine hydroxylase TET2, that have previously been linked to the pathogenesis of IDH mutant tumors. We provide evidence that this paradox relates to the ability of (S)-2HG, but not (R)-2HG, to inhibit the EglN prolyl hydroxylases. Additionally, we show that transformation by (R)-2HG is reversible.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836459/" 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/PMC3836459/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Losman, Julie-Aurore -- Looper, Ryan E -- Koivunen, Peppi -- Lee, Sungwoo -- Schneider, Rebekka K -- McMahon, Christine -- Cowley, Glenn S -- Root, David E -- Ebert, Benjamin L -- Kaelin, William G Jr -- P30 DK049216/DK/NIDDK NIH HHS/ -- R01 CA068490/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Mar 29;339(6127):1621-5. doi: 10.1126/science.1231677. Epub 2013 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393090" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*metabolism ; Glutarates/*metabolism ; *Hematopoiesis ; Humans ; Isocitrate Dehydrogenase/genetics/*metabolism ; Leukemia/*enzymology/genetics ; Models, Biological ; Procollagen-Proline Dioxygenase/*antagonists & inhibitors
    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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  • 3
    Publication Date: 2015-06-13
    Description: The distribution and interactions of aquatic organisms across space and time structure our marine, freshwater, and estuarine ecosystems. Over the past decade, technological advances in telemetry have transformed our ability to observe aquatic animal behavior and movement. These advances are now providing unprecedented ecological insights by connecting animal movements with measures of their physiology and environment. These developments are revolutionizing the scope and scale of questions that can be asked about the causes and consequences of movement and are redefining how we view and manage individuals, populations, and entire ecosystems. The next advance in aquatic telemetry will be the development of a global collaborative effort to facilitate infrastructure and data sharing and management over scales not previously possible.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hussey, Nigel E -- Kessel, Steven T -- Aarestrup, Kim -- Cooke, Steven J -- Cowley, Paul D -- Fisk, Aaron T -- Harcourt, Robert G -- Holland, Kim N -- Iverson, Sara J -- Kocik, John F -- Mills Flemming, Joanna E -- Whoriskey, Fred G -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1255642. doi: 10.1126/science.1255642. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Great Lakes Institute for Environmental Research, University of Windsor, 401 Sunset Avenue, Windsor, Ontario N9B 3P4, Canada. ; National Institute of Aquatic Resources, Technical University of Denmark, Vejlsoevej 39, DK-8600 Silkeborg, Denmark. ; Fish Ecology and Conservation Physiology Laboratory, Department of Biology and Institute of Environmental Science, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. ; South African Institute for Aquatic Biodiversity, Private Bag 1015, Grahamstown 6140, South Africa. ; Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia. ; Hawaii Institute of Marine Biology, University of Hawaii at Manoa, Kane'ohe, HI 96744, USA. ; Ocean Tracking Network, Department of Biology, Dalhousie University, 1355 Oxford Road, Halifax, Nova Scotia B3H 4R2, Canada. sara.iverson@dal.ca. ; Northeast Fisheries Science Center, National Oceanic and Atmospheric Administration Fisheries, 17 Godfrey Drive, Orono, ME 04473, USA. ; Department of Mathematics and Statistics, Dalhousie University, 6316 Coburg Road, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada. ; Ocean Tracking Network, Department of Biology, Dalhousie University, 1355 Oxford Road, Halifax, Nova Scotia B3H 4R2, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068859" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Distribution ; Animals ; Aquatic Organisms/*physiology ; Endangered Species ; Environmental Monitoring/*methods ; Movement ; Telemetry/*methods/*trends
    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
    Publication Date: 2016-02-26
    Description: The discovery of cancer dependencies has the potential to inform therapeutic strategies and to identify putative drug targets. Integrating data from comprehensive genomic profiling of cancer cell lines and from functional characterization of cancer cell dependencies, we discovered that loss of the enzyme methylthioadenosine phosphorylase (MTAP) confers a selective dependence on protein arginine methyltransferase 5 (PRMT5) and its binding partner WDR77. MTAP is frequently lost due to its proximity to the commonly deleted tumor suppressor gene, CDKN2A. We observed increased intracellular concentrations of methylthioadenosine (MTA, the metabolite cleaved by MTAP) in cells harboring MTAP deletions. Furthermore, MTA specifically inhibited PRMT5 enzymatic activity. Administration of either MTA or a small-molecule PRMT5 inhibitor showed a modest preferential impairment of cell viability for MTAP-null cancer cell lines compared with isogenic MTAP-expressing counterparts. Together, our findings reveal PRMT5 as a potential vulnerability across multiple cancer lineages augmented by a common "passenger" genomic alteration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kryukov, Gregory V -- Wilson, Frederick H -- Ruth, Jason R -- Paulk, Joshiawa -- Tsherniak, Aviad -- Marlow, Sara E -- Vazquez, Francisca -- Weir, Barbara A -- Fitzgerald, Mark E -- Tanaka, Minoru -- Bielski, Craig M -- Scott, Justin M -- Dennis, Courtney -- Cowley, Glenn S -- Boehm, Jesse S -- Root, David E -- Golub, Todd R -- Clish, Clary B -- Bradner, James E -- Hahn, William C -- Garraway, Levi A -- KL2 TR001100/TR/NCATS NIH HHS/ -- U01 CA176058/CA/NCI NIH HHS/ -- U54 CA112962/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1214-8. doi: 10.1126/science.aad5214. Epub 2016 Feb 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. levi_garraway@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912360" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line, Tumor ; Deoxyadenosines/metabolism/pharmacology ; Enzyme Inhibitors/pharmacology ; Gene Deletion ; Humans ; Isoquinolines/pharmacology ; Neoplasms/*drug therapy/enzymology ; Protein-Arginine N-Methyltransferases/antagonists & ; inhibitors/genetics/*metabolism ; Purine-Nucleoside Phosphorylase/genetics/*metabolism ; Pyrimidines/pharmacology ; Thionucleosides/metabolism/pharmacology ; Transcription Factors
    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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