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  • Articles  (1,470)
  • Latest Papers from Table of Contents or Articles in Press  (1,470)
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  • Articles  (1,470)
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  • Latest Papers from Table of Contents or Articles in Press  (1,470)
  • Articles: DFG German National Licenses
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  • 1
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    Novel mutant-selective EGFR kinase inhibitors against EGFR T790M (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-25
    Description: The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clinically more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacological screens against clinically important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879581/" 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/PMC2879581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Wenjun -- Ercan, Dalia -- Chen, Liang -- Yun, Cai-Hong -- Li, Danan -- Capelletti, Marzia -- Cortot, Alexis B -- Chirieac, Lucian -- Iacob, Roxana E -- Padera, Robert -- Engen, John R -- Wong, Kwok-Kin -- Eck, Michael J -- Gray, Nathanael S -- Janne, Pasi A -- P50CA090578/CA/NCI NIH HHS/ -- R01 CA122794/CA/NCI NIH HHS/ -- R01 CA130876/CA/NCI NIH HHS/ -- R01 CA130876-02/CA/NCI NIH HHS/ -- R01 CA135257/CA/NCI NIH HHS/ -- R01AG2400401/AG/NIA NIH HHS/ -- R01CA080942/CA/NCI NIH HHS/ -- R01CA11446/CA/NCI NIH HHS/ -- R01CA116020/CA/NCI NIH HHS/ -- R01CA130876-02/CA/NCI NIH HHS/ -- R01CA135257/CA/NCI NIH HHS/ -- R01GM070590/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 24;462(7276):1070-4. doi: 10.1038/nature08622.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033049" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/chemistry/*pharmacology/toxicity ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Evaluation, Preclinical ; Drug Resistance, Neoplasm/genetics ; Lung/drug effects ; Mice ; Models, Chemical ; Models, Molecular ; Mutation/*genetics ; NIH 3T3 Cells ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/chemistry/*pharmacology/toxicity ; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/*genetics
    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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  • 2
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    Structural biology: Translocation chamber's secrets (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-25
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873764/" 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/PMC3873764/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christie, Peter J -- R01 GM048746/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 24;462(7276):992-4. doi: 10.1038/462992b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033031" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/chemistry/*metabolism ; Conjugation, Genetic/*physiology ; DNA, Bacterial/*metabolism ; Escherichia coli Proteins/*chemistry/*metabolism ; Models, Molecular ; Protein Structure, Quaternary
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-25
    Description: Sequencing of bacterial and archaeal genomes has revolutionized our understanding of the many roles played by microorganisms. There are now nearly 1,000 completed bacterial and archaeal genomes available, most of which were chosen for sequencing on the basis of their physiology. As a result, the perspective provided by the currently available genomes is limited by a highly biased phylogenetic distribution. To explore the value added by choosing microbial genomes for sequencing on the basis of their evolutionary relationships, we have sequenced and analysed the genomes of 56 culturable species of Bacteria and Archaea selected to maximize phylogenetic coverage. Analysis of these genomes demonstrated pronounced benefits (compared to an equivalent set of genomes randomly selected from the existing database) in diverse areas including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. Our results strongly support the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' in order to derive maximum knowledge from existing microbial genome data as well as from genome sequences to come.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073058/" 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/PMC3073058/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Dongying -- Hugenholtz, Philip -- Mavromatis, Konstantinos -- Pukall, Rudiger -- Dalin, Eileen -- Ivanova, Natalia N -- Kunin, Victor -- Goodwin, Lynne -- Wu, Martin -- Tindall, Brian J -- Hooper, Sean D -- Pati, Amrita -- Lykidis, Athanasios -- Spring, Stefan -- Anderson, Iain J -- D'haeseleer, Patrik -- Zemla, Adam -- Singer, Mitchell -- Lapidus, Alla -- Nolan, Matt -- Copeland, Alex -- Han, Cliff -- Chen, Feng -- Cheng, Jan-Fang -- Lucas, Susan -- Kerfeld, Cheryl -- Lang, Elke -- Gronow, Sabine -- Chain, Patrick -- Bruce, David -- Rubin, Edward M -- Kyrpides, Nikos C -- Klenk, Hans-Peter -- Eisen, Jonathan A -- R01 GM054592-09/GM/NIGMS NIH HHS/ -- R01 GM067012-04/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 24;462(7276):1056-60. doi: 10.1038/nature08656.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DOE Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033048" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry ; Amino Acid Sequence ; Archaea/*classification/*genetics ; Bacteria/*classification/*genetics ; Bacterial Proteins/chemistry ; Biodiversity ; Databases, Genetic ; Genes, rRNA/genetics ; Genome, Archaeal/*genetics ; Genome, Bacterial/*genetics ; Models, Molecular ; Molecular Sequence Data ; *Phylogeny ; Protein Structure, Tertiary ; Sequence Alignment
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-12-22
    Description: Broken chromosomes arising from DNA double-strand breaks result from endogenous events such as the production of reactive oxygen species during cellular metabolism, as well as from exogenous sources such as ionizing radiation. Left unrepaired or incorrectly repaired they can lead to genomic changes that may result in cell death or cancer. DNA-dependent protein kinase (DNA-PK), a holoenzyme that comprises the DNA-PK catalytic subunit (DNA-PKcs) and the heterodimer Ku70/Ku80, has a major role in non-homologous end joining-the main pathway in mammals used to repair double-strand breaks. DNA-PKcs is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids and belonging to the phosphatidylinositol-3-OH kinase (PI(3)K)-related protein family. DNA-PKcs is involved in the sensing and transmission of DNA damage signals to proteins such as p53, setting off events that lead to cell cycle arrest. It phosphorylates a wide range of substrates in vitro, including Ku70/Ku80, which is translocated along DNA. Here we present the crystal structure of human DNA-PKcs at 6.6 A resolution, in which the overall fold is clearly visible, to our knowledge, for the first time. The many alpha-helical HEAT repeats (helix-turn-helix motifs) facilitate bending and allow the polypeptide chain to fold into a hollow circular structure. The carboxy-terminal kinase domain is located on top of this structure, and a small HEAT repeat domain that probably binds DNA is inside. The structure provides a flexible cradle to promote DNA double-strand-break repair.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811870/" 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/PMC2811870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sibanda, Bancinyane L -- Chirgadze, Dimitri Y -- Blundell, Tom L -- 079281/Wellcome Trust/United Kingdom -- A3846/Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jan 7;463(7277):118-21. doi: 10.1038/nature08648. Epub 2009 Dec 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, Old Addenbrooke's site, 80 Tennis Court Road, Cambridge CB2 1GA, UK. lynn@cryst.bioc.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20023628" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Nuclear/chemistry ; Catalytic Domain ; Crystallography, X-Ray ; DNA/metabolism ; DNA Breaks, Double-Stranded ; DNA-Activated Protein Kinase/*chemistry/metabolism ; DNA-Binding Proteins/chemistry ; HeLa Cells ; *Helix-Turn-Helix Motifs ; Humans ; Models, Molecular ; Nuclear Proteins/*chemistry/metabolism ; Protein Folding ; Protein Structure, Secondary
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
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    The subtle transmission of race bias via televised nonverbal behavior (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: Compared with more explicit racial slurs and statements, biased facial expressions and body language may resist conscious identification and thus produce a hidden social influence. In four studies, we show that race biases can be subtly transmitted via televised nonverbal behavior. Characters on 11 popular television shows exhibited more negative nonverbal behavior toward black than toward status-matched white characters. Critically, exposure to prowhite (versus problack) nonverbal bias increased viewers' bias even though patterns of nonverbal behavior could not be consciously reported. These findings suggest that hidden patterns of televised nonverbal behavior influence bias among viewers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764987/" 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/PMC3764987/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weisbuch, Max -- Pauker, Kristin -- Ambady, Nalini -- F32 MH078350/MH/NIMH NIH HHS/ -- F32MH078350/MH/NIMH NIH HHS/ -- R01 MH070833/MH/NIMH NIH HHS/ -- R01 MH070833-02/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1711-4. doi: 10.1126/science.1178358.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Tufts University, 490 Boston Avenue, Medford, MA 02155, USA. max.weisbuch@tufts.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019288" target="_blank"〉PubMed〈/a〉
    Keywords: *African Continental Ancestry Group ; Cues ; *European Continental Ancestry Group ; Facial Expression ; Female ; Humans ; Kinesics ; Male ; *Nonverbal Communication ; *Prejudice ; *Television ; United States
    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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  • 6
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    Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: Inward-rectifier potassium (K+) channels conduct K+ ions most efficiently in one direction, into the cell. Kir2 channels control the resting membrane voltage in many electrically excitable cells, and heritable mutations cause periodic paralysis and cardiac arrhythmia. We present the crystal structure of Kir2.2 from chicken, which, excluding the unstructured amino and carboxyl termini, is 90% identical to human Kir2.2. Crystals containing rubidium (Rb+), strontium (Sr2+), and europium (Eu3+) reveal binding sites along the ion conduction pathway that are both conductive and inhibitory. The sites correlate with extensive electrophysiological data and provide a structural basis for understanding rectification. The channel's extracellular surface, with large structured turrets and an unusual selectivity filter entryway, might explain the relative insensitivity of eukaryotic inward rectifiers to toxins. These same surface features also suggest a possible approach to the development of inhibitory agents specific to each member of the inward-rectifier K+ channel family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819303/" 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/PMC2819303/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tao, Xiao -- Avalos, Jose L -- Chen, Jiayun -- MacKinnon, Roderick -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 GM043949/GM/NIGMS NIH HHS/ -- R01 GM043949-10/GM/NIGMS NIH HHS/ -- R01 GM043949-11/GM/NIGMS NIH HHS/ -- R01 GM043949-12/GM/NIGMS NIH HHS/ -- R01 GM043949-13/GM/NIGMS NIH HHS/ -- R01 GM043949-14/GM/NIGMS NIH HHS/ -- R01 GM043949-15/GM/NIGMS NIH HHS/ -- R01 GM043949-16/GM/NIGMS NIH HHS/ -- R01 GM043949-17/GM/NIGMS NIH HHS/ -- R01 GM043949-18/GM/NIGMS NIH HHS/ -- R01 GM043949-19/GM/NIGMS NIH HHS/ -- R01 GM043949-20/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1668-74. doi: 10.1126/science.1180310.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019282" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Binding Sites ; Chickens ; Cloning, Molecular ; Crystallography, X-Ray ; Europium/metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Molecular Sequence Data ; Oocytes ; Patch-Clamp Techniques ; Potassium/metabolism ; Potassium Channel Blockers/pharmacology ; Potassium Channels, Inwardly Rectifying/antagonists & ; inhibitors/*chemistry/metabolism ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Rubidium/metabolism ; Sequence Alignment ; Strontium/metabolism ; Xenopus laevis
    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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  • 7
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    Evolution. Sexual selection and Darwin's mystery of mysteries (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mank, Judith E -- New York, N.Y. -- Science. 2009 Dec 18;326(5960):1639-40. doi: 10.1126/science.1184680.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Oxford, Edward Grey Institute, Oxford OX1 3PS, UK. judith.mank@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019275" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; *Biological Evolution ; Ecosystem ; Female ; Fishes/anatomy & histology/genetics ; Gene Flow ; *Genetic Speciation ; Geography ; Male ; *Mating Preference, Animal ; *Models, Biological ; Selection, Genetic
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Objective confirmation of subjective measures of human well-being: evidence from the U.S.A (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-12-19
    Description: A huge research literature, across the behavioral and social sciences, uses information on individuals' subjective well-being. These are responses to questions--asked by survey interviewers or medical personnel--such as, "How happy do you feel on a scale from 1 to 4?" Yet there is little scientific evidence that such data are meaningful. This study examines a 2005-2008 Behavioral Risk Factor Surveillance System random sample of 1.3 million U.S. citizens. Life satisfaction in each U.S. state is measured. Across America, people's answers trace out the same pattern of quality of life as previously estimated, from solely nonsubjective data, in one branch of economics (so-called "compensating differentials" neoclassical theory, originally from Adam Smith). There is a state-by-state match (r = 0.6, P 〈 0.001) between subjective and objective well-being. This result has some potential to help to unify disciplines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oswald, Andrew J -- Wu, Stephen -- New York, N.Y. -- Science. 2010 Jan 29;327(5965):576-9. doi: 10.1126/science.1180606. Epub 2009 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Economics, University of Warwick, Coventry CV4 7AL, UK. andrew.oswald@warwick.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20019249" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Economics ; Female ; *Happiness ; *Health Surveys ; Humans ; *Income ; Male ; Models, Economic ; *Personal Satisfaction ; *Quality of Life ; Regression Analysis ; *Socioeconomic Factors ; Surveys and Questionnaires ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    A comprehensive catalogue of somatic mutations from a human cancer genome (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-12-18
    Description: All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145108/" 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/PMC3145108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pleasance, Erin D -- Cheetham, R Keira -- Stephens, Philip J -- McBride, David J -- Humphray, Sean J -- Greenman, Chris D -- Varela, Ignacio -- Lin, Meng-Lay -- Ordonez, Gonzalo R -- Bignell, Graham R -- Ye, Kai -- Alipaz, Julie -- Bauer, Markus J -- Beare, David -- Butler, Adam -- Carter, Richard J -- Chen, Lina -- Cox, Anthony J -- Edkins, Sarah -- Kokko-Gonzales, Paula I -- Gormley, Niall A -- Grocock, Russell J -- Haudenschild, Christian D -- Hims, Matthew M -- James, Terena -- Jia, Mingming -- Kingsbury, Zoya -- Leroy, Catherine -- Marshall, John -- Menzies, Andrew -- Mudie, Laura J -- Ning, Zemin -- Royce, Tom -- Schulz-Trieglaff, Ole B -- Spiridou, Anastassia -- Stebbings, Lucy A -- Szajkowski, Lukasz -- Teague, Jon -- Williamson, David -- Chin, Lynda -- Ross, Mark T -- Campbell, Peter J -- Bentley, David R -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jan 14;463(7278):191-6. doi: 10.1038/nature08658. Epub 2009 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016485" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Mutational Analysis ; DNA Repair/genetics ; Gene Dosage/genetics ; Genes, Neoplasm/*genetics ; Genome, Human/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Male ; Melanoma/etiology/genetics ; MicroRNAs/genetics ; Mutagenesis, Insertional/genetics ; Mutation/*genetics ; Neoplasms/etiology/*genetics ; Polymorphism, Single Nucleotide/genetics ; Precision Medicine ; Sequence Deletion/genetics ; Ultraviolet Rays
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Parental origin of sequence variants associated with complex diseases (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-12-18
    Description: Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746295/" 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/PMC3746295/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Augustine -- Steinthorsdottir, Valgerdur -- Masson, Gisli -- Thorleifsson, Gudmar -- Sulem, Patrick -- Besenbacher, Soren -- Jonasdottir, Aslaug -- Sigurdsson, Asgeir -- Kristinsson, Kari Th -- Jonasdottir, Adalbjorg -- Frigge, Michael L -- Gylfason, Arnaldur -- Olason, Pall I -- Gudjonsson, Sigurjon A -- Sverrisson, Sverrir -- Stacey, Simon N -- Sigurgeirsson, Bardur -- Benediktsdottir, Kristrun R -- Sigurdsson, Helgi -- Jonsson, Thorvaldur -- Benediktsson, Rafn -- Olafsson, Jon H -- Johannsson, Oskar Th -- Hreidarsson, Astradur B -- Sigurdsson, Gunnar -- DIAGRAM Consortium -- Ferguson-Smith, Anne C -- Gudbjartsson, Daniel F -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- 077016/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- G9723500/Medical Research Council/United Kingdom -- K08 AR055688/AR/NIAMS NIH HHS/ -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106179474/Medical Research Council/United Kingdom -- MC_U127592696/Medical Research Council/United Kingdom -- R01 DK029867/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):868-74. doi: 10.1038/nature08625.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. kong@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016592" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Binding Sites ; Breast Neoplasms/genetics ; Carcinoma, Basal Cell/genetics ; Chromosomes, Human, Pair 11/genetics ; Chromosomes, Human, Pair 7/genetics ; DNA Methylation/genetics ; Diabetes Mellitus, Type 2/genetics ; *Fathers ; Female ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Genomic Imprinting/genetics ; Haplotypes ; Humans ; Iceland ; Male ; *Mothers ; Pedigree ; Polymorphism, Single Nucleotide/*genetics ; Repressor Proteins/metabolism
    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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