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  • Articles  (52)
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Journal
  • 1
    Publication Date: 2011-10-12
    Description: To catalog protein-altering mutations that may drive the development of prostate cancers and their progression to metastatic disease systematically, we performed whole-exome sequencing of 23 prostate cancers derived from 16 different lethal metastatic tumors and three high-grade primary carcinomas. All tumors were propagated in mice as xenografts, designated the LuCaP series, to model phenotypic variation, such as responses to cancer-directed therapeutics. Although corresponding normal tissue was not available for most tumors, we were able to take advantage of increasingly deep catalogs of human genetic variation to remove most germline variants. On average, each tumor genome contained ∼200 novel nonsynonymous variants, of which the vast majority was specific to individual carcinomas. A subset of genes was recurrently altered across tumors derived from different individuals, including TP53, DLK2, GPC6, and SDF4. Unexpectedly, three prostate cancer genomes exhibited substantially higher mutation frequencies, with 2,000–4,000 novel coding variants per exome. A comparison of castration-resistant and castration-sensitive pairs of tumor lines derived from the same prostate cancer highlights mutations in the Wnt pathway as potentially contributing to the development of castration resistance. Collectively, our results indicate that point mutations arising in coding regions of advanced prostate cancers are common but, with notable exceptions, very few genes are mutated in a substantial fraction of tumors. We also report a previously undescribed subtype of prostate cancers exhibiting “hypermutated” genomes, with potential implications for resistance to cancer therapeutics. Our results also suggest that increasingly deep catalogs of human germline variation may challenge the necessity of sequencing matched tumor-normal pairs.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2013-07-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCouch, Susan -- Baute, Gregory J -- Bradeen, James -- Bramel, Paula -- Bretting, Peter K -- Buckler, Edward -- Burke, John M -- Charest, David -- Cloutier, Sylvie -- Cole, Glenn -- Dempewolf, Hannes -- Dingkuhn, Michael -- Feuillet, Catherine -- Gepts, Paul -- Grattapaglia, Dario -- Guarino, Luigi -- Jackson, Scott -- Knapp, Sandra -- Langridge, Peter -- Lawton-Rauh, Amy -- Lijua, Qui -- Lusty, Charlotte -- Michael, Todd -- Myles, Sean -- Naito, Ken -- Nelson, Randall L -- Pontarollo, Reno -- Richards, Christopher M -- Rieseberg, Loren -- Ross-Ibarra, Jeffrey -- Rounsley, Steve -- Hamilton, Ruaraidh Sackville -- Schurr, Ulrich -- Stein, Nils -- Tomooka, Norihiko -- van der Knaap, Esther -- van Tassel, David -- Toll, Jane -- Valls, Jose -- Varshney, Rajeev K -- Ward, Judson -- Waugh, Robbie -- Wenzl, Peter -- Zamir, Daniel -- England -- Nature. 2013 Jul 4;499(7456):23-4. doi: 10.1038/499023a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cornell University, Ithaca, New York, USA. mccouch@cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823779" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/genetics ; Agriculture/economics/*methods/*trends ; Biodiversity ; Biological Specimen Banks ; Breeding ; Crops, Agricultural/genetics ; Food Supply/*statistics & numerical data ; Genes, Plant ; Humans ; Phenotype ; Seeds/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-05-09
    Description: Dietary deficiencies of zinc and iron are a substantial global public health problem. An estimated two billion people suffer these deficiencies, causing a loss of 63 million life-years annually. Most of these people depend on C3 grains and legumes as their primary dietary source of zinc and iron. Here we report that C3 grains and legumes have lower concentrations of zinc and iron when grown under field conditions at the elevated atmospheric CO2 concentration predicted for the middle of this century. C3 crops other than legumes also have lower concentrations of protein, whereas C4 crops seem to be less affected. Differences between cultivars of a single crop suggest that breeding for decreased sensitivity to atmospheric CO2 concentration could partly address these new challenges to global health.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myers, Samuel S -- Zanobetti, Antonella -- Kloog, Itai -- Huybers, Peter -- Leakey, Andrew D B -- Bloom, Arnold J -- Carlisle, Eli -- Dietterich, Lee H -- Fitzgerald, Glenn -- Hasegawa, Toshihiro -- Holbrook, N Michele -- Nelson, Randall L -- Ottman, Michael J -- Raboy, Victor -- Sakai, Hidemitsu -- Sartor, Karla A -- Schwartz, Joel -- Seneweera, Saman -- Tausz, Michael -- Usui, Yasuhiro -- 8UL1TR000170-0/TR/NCATS NIH HHS/ -- P30 ES000002/ES/NIEHS NIH HHS/ -- UL1 TR000170/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Jun 5;510(7503):139-42. doi: 10.1038/nature13179. Epub 2014 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, 02215, USA [2] Harvard University Center for the Environment, Cambridge, Massachusetts 02138, USA. ; Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, 02215, USA. ; The Department of Geography and Environmental Development, Ben-Gurion University of the Negev, PO Box 653, Beer Sheva, Israel. ; Department of Earth and Planetary Science, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Plant Biology and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Department of Plant Sciences, University of California at Davis, Davis, California 95616, USA. ; University of Pennsylvania, Department of Biology, Philadelphia, Pennsylvania 19104, USA. ; Department of Environment and Primary Industries, Horsham, Victoria 3001, Australia. ; National Institute for Agro-Environmental Sciences, Tsukuba, Ibaraki, 305-8604, Japan. ; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; United States Department of Agriculture Agricultural Research Service, Soybean/Maize Germplasm, Pathology, and Genetics Research Unit, Department of Crop Sciences, University of Illinois, Urbana, Illinois 61801, USA. ; School of Plant Sciences, University of Arizona, Tucson, Arizona 85721, USA. ; United States Department of Agriculture Agricultural Research Service, Aberdeen, Idaho 83210, USA. ; The Nature Conservancy, Santa Fe, New Mexico 87544, USA. ; Department of Agriculture and Food Systems, Melbourne School of Land and Environment, The University of Melbourne, Creswick, Victoria 3363, Australia. ; Department of Forest and Ecosystem Science, Melbourne School of Land and Environment, The University of Melbourne, Creswick, Victoria 3363, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805231" target="_blank"〉PubMed〈/a〉
    Keywords: Air/analysis ; Atmosphere/chemistry ; Australia ; Breeding ; Carbon Dioxide/analysis/*pharmacology ; Crops, Agricultural/*chemistry/*drug effects/metabolism ; Diet ; Edible Grain/chemistry/drug effects/metabolism ; Fabaceae/chemistry/drug effects/metabolism ; Global Health/trends ; Humans ; Iron/analysis/deficiency/metabolism ; Japan ; *Nutritional Status ; Nutritive Value/*drug effects ; Photosynthesis/drug effects ; Phytic Acid/analysis/metabolism ; Public Health/*trends ; United States ; Zinc/analysis/deficiency/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1989-10-13
    Description: Fumigant applicators who, 6 weeks to 3 months earlier, were exposed to phosphine, a common grain fumigant, or to phosphine and other pesticides had significantly increased stable chromosome rearrangements, primarily translocations in G-banded lymphocytes. Less stable aberrations including chromatid deletions and gaps were significantly increased only during the application season, but not at this later time point. During fumigant application, measured exposure to phosphine exceeds accepted national standards. Because phosphine is also used as a dopant in the microchip industry and is generated in waste treatment, the possibility of more widespread exposure and long-term health sequelae must be considered.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garry, V F -- Griffith, J -- Danzl, T J -- Nelson, R L -- Whorton, E B -- Krueger, L A -- Cervenka, J -- New York, N.Y. -- Science. 1989 Oct 13;246(4927):251-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55414.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2799386" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosome Aberrations ; Chromosome Banding ; Environmental Exposure ; Humans ; Lymphocytes/drug effects/ultrastructure ; Male ; Pesticides/*poisoning ; Phosphines/*poisoning
    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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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 22 (1977), S. 303-313 
    ISSN: 1432-0827
    Keywords: Osteoclasts ; Sedimentation ; Isolation ; Cells ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract A method is presented for separating osteoclasts from the heterogeneous population of bone and marrow cells. Cell suspensions were prepared from femora of young rabbits by mechanical dispersion. The starting cell suspension typically contained only 1.0%±0.5 osteoclasts. Following an initial 45 min of unit gravity sedimentation in a lucite chamber osteoclasts were primarily distributed in fractions 2–5. A second 45-min sedimentation of these pooled fractions yielded cell suspensions containing greater than 30% osteoclasts (as much as a 50-fold increase over starting percentages). Linear scan analysis, however, revealed that osteoclasts accounted for 73.14%±0.58 of the cell colume. Subsequent in vitro experiments demonstrated linear incorporation of3H-leucine into TCA precipitable protein for cells comprising the osteoclast fraction. Concomitant radiautographs revealed radioactive label in isolated osteoclasts.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 × 13 × 13 km. Following the completion of its ...
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 235 (1972), S. 278-280 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] More recently, normal Syrian hamster embryo cells have been used to determine directly the frequency of transformation by chemical carcinogens5,6. This phenomenon is inductive rather than selective, as the increase in frequency of transformation on a per cell basis is proportional to concentration ...
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-4927
    Keywords: starch gel electrophoresis ; L-glutamate dehydrogenase (GLUD)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A method for the starch gel electrophoresis of human L-glutamate dehydrogenase (GLUD) is described, as is the tissue distribution of GLUD detected by this method. Extracts of livers from 200 Whites were analyzed without demonstration of an electrophoretic variant. The molecular size was estimated to be 330,000 and the isoelectric point pH 4.83.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-4927
    Keywords: ammonia metabolism, enzymes of ; L-glutamate dehydrogenase as a linking enzyme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The use of L-glutamate dehydrogenase (GLUD) as a reagent in staining mixtures to detect the isozymes of enzymes which catalyze the production of ammonia has been investigated. Methods have been devised for the electrophoresis and detection, using GLUD, of seven enzymes: cytidine deaminase, adenosine deaminase, adenosine monophosphate deaminase, arginase, argininosuccinase, D-amino acid oxidase, and D-aspartate oxidase. GLUD-linked staining methods appear to be sensitive, specific, and of general application.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 3 (1957), S. 7S 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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