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  • Reproducibility of Results  (55)
  • Nature Publishing Group (NPG)  (55)
  • Elsevier
  • MDPI Publishing
  • 2010-2014  (55)
  • 2012  (55)
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  • 2010-2014  (55)
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  • 1
    Publication Date: 2012-10-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Snowdon, Rod -- Friedt, Wolfgang -- England -- Nature. 2012 Oct 4;490(7418):37. doi: 10.1038/490037d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23038458" target="_blank"〉PubMed〈/a〉
    Keywords: Biofuels/economics/statistics & numerical data/*supply & distribution ; Brassica rapa/chemistry/growth & development ; Europe ; *European Union ; Plant Oils/economics/*supply & distribution ; Reproducibility of Results ; Seeds/chemistry/growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    Nature Publishing Group (NPG)
    Publication Date: 2012-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2012 Apr 25;484(7395):428. doi: 10.1038/484428a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22538578" target="_blank"〉PubMed〈/a〉
    Keywords: Data Interpretation, Statistical ; Genomic Imprinting/*genetics ; *High-Throughput Nucleotide Sequencing/methods ; Models, Genetic ; Polymorphism, Single Nucleotide/genetics ; RNA/*genetics ; RNA Editing/genetics ; Reproducibility of Results ; *Sequence Analysis, RNA/methods
    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: 2012-03-20
    Description: Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385933/" 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/PMC3385933/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Zhao -- Cheng, Katherine -- Walton, Zandra -- Wang, Yuchuan -- Ebi, Hiromichi -- Shimamura, Takeshi -- Liu, Yan -- Tupper, Tanya -- Ouyang, Jing -- Li, Jie -- Gao, Peng -- Woo, Michele S -- Xu, Chunxiao -- Yanagita, Masahiko -- Altabef, Abigail -- Wang, Shumei -- Lee, Charles -- Nakada, Yuji -- Pena, Christopher G -- Sun, Yanping -- Franchetti, Yoko -- Yao, Catherine -- Saur, Amy -- Cameron, Michael D -- Nishino, Mizuki -- Hayes, D Neil -- Wilkerson, Matthew D -- Roberts, Patrick J -- Lee, Carrie B -- Bardeesy, Nabeel -- Butaney, Mohit -- Chirieac, Lucian R -- Costa, Daniel B -- Jackman, David -- Sharpless, Norman E -- Castrillon, Diego H -- Demetri, George D -- Janne, Pasi A -- Pandolfi, Pier Paolo -- Cantley, Lewis C -- Kung, Andrew L -- Engelman, Jeffrey A -- Wong, Kwok-Kin -- 1U01CA141576/CA/NCI NIH HHS/ -- CA122794/CA/NCI NIH HHS/ -- CA137008/CA/NCI NIH HHS/ -- CA137008-01/CA/NCI NIH HHS/ -- CA137181/CA/NCI NIH HHS/ -- CA140594/CA/NCI NIH HHS/ -- CA147940/CA/NCI NIH HHS/ -- K23 CA157631/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- P50 CA090578/CA/NCI NIH HHS/ -- P50 CA090578-06/CA/NCI NIH HHS/ -- P50CA090578/CA/NCI NIH HHS/ -- R01 CA122794/CA/NCI NIH HHS/ -- R01 CA122794-01/CA/NCI NIH HHS/ -- R01 CA137008/CA/NCI NIH HHS/ -- R01 CA137008-01/CA/NCI NIH HHS/ -- R01 CA137181/CA/NCI NIH HHS/ -- R01 CA137181-01A2/CA/NCI NIH HHS/ -- R01 CA140594/CA/NCI NIH HHS/ -- R01 CA140594-01/CA/NCI NIH HHS/ -- R01 CA163896/CA/NCI NIH HHS/ -- RC2 CA147940/CA/NCI NIH HHS/ -- RC2 CA147940-01/CA/NCI NIH HHS/ -- U01 CA141576/CA/NCI NIH HHS/ -- U01 CA141576-01/CA/NCI NIH HHS/ -- England -- Nature. 2012 Mar 18;483(7391):613-7. doi: 10.1038/nature10937.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22425996" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Combined Chemotherapy Protocols ; Benzimidazoles/*pharmacology/therapeutic use ; Biomarkers, Tumor/genetics/metabolism ; *Clinical Trials, Phase II as Topic ; *Disease Models, Animal ; Drug Evaluation, Preclinical ; Fluorodeoxyglucose F18 ; Genes, p53/genetics ; Humans ; Lung Neoplasms/*drug therapy/enzymology/*genetics/metabolism ; MAP Kinase Signaling System/drug effects ; Mice ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors ; Mutation/genetics ; Pharmacogenetics/*methods ; Positron-Emission Tomography ; Protein-Serine-Threonine Kinases/deficiency/genetics ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Taxoids/*therapeutic use ; Tomography, X-Ray Computed ; Treatment Outcome ; ras Proteins/genetics/metabolism
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  • 4
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    Nature Publishing Group (NPG)
    Publication Date: 2012-09-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Sep 20;489(7416):335-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23002452" target="_blank"〉PubMed〈/a〉
    Keywords: Disasters/economics/prevention & control/*statistics & numerical data ; Global Warming/economics/legislation & jurisprudence/prevention & ; control/*statistics & numerical data ; Liability, Legal ; *Models, Theoretical ; Policy Making ; Probability ; Reproducibility of Results
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-04-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baumgartner, Holger -- England -- Nature. 2012 Apr 4;484(7392):37. doi: 10.1038/484037d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22481345" target="_blank"〉PubMed〈/a〉
    Keywords: *Ethics, Research ; Humans ; *Periodicals as Topic ; Publishing/*standards ; Reproducibility of Results ; Retraction of Publication as Topic ; Scientific Misconduct
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2012-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sarewitz, Daniel -- England -- Nature. 2012 May 9;485(7397):149. doi: 10.1038/485149a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Consortium for Science, Policy and Outcomes, Arizona State University, USA. dsarewitz@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575922" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bias (Epidemiology) ; Biomedical Research/standards ; Humans ; Mice ; Models, Animal ; *Public Opinion ; Reproducibility of Results ; Research/*standards ; *Research Design ; *Trust
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2012-09-18
    Description: Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" 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/PMC3556990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Litvak, Vladimir -- Ratushny, Alexander V -- Lampano, Aaron E -- Schmitz, Frank -- Huang, Albert C -- Raman, Ayush -- Rust, Alistair G -- Bergthaler, Andreas -- Aitchison, John D -- Aderem, Alan -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272200800058C/AI/NIAID NIH HHS/ -- HSN272200800058C/PHS HHS/ -- R01 AI025032/AI/NIAID NIH HHS/ -- R01 AI032972/AI/NIAID NIH HHS/ -- R01AI025032/AI/NIAID NIH HHS/ -- R01AI032972/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 GM103511/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- U54GM103511/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Forkhead Transcription Factors/deficiency/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation/*immunology ; Inflammation/genetics/*immunology/*pathology ; Interferon Regulatory Factor-7/deficiency/genetics/*metabolism ; Interferon Type I/immunology ; Lung/immunology/pathology/virology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Reproducibility of Results ; Vesiculovirus/*immunology
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  • 8
    Publication Date: 2012-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolker, Jessica -- England -- Nature. 2012 Nov 1;491(7422):31-3. doi: 10.1038/491031a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of New Hampshire, Durham 03824, New Hampshire, USA. jessica.bolker@unh.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128209" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Laboratory ; Arabidopsis ; Caenorhabditis elegans ; Disease Models, Animal ; Drosophila melanogaster/genetics/growth & development/physiology ; Environment ; Genotype ; Mice ; *Models, Animal ; *Models, Biological ; Phenotype ; Rats ; Reproducibility of Results ; Research Design/*standards ; Species Specificity
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2012-02-24
    Description: Scientific communication relies on evidence that cannot be entirely included in publications, but the rise of computational science has added a new layer of inaccessibility. Although it is now accepted that data should be made available on request, the current regulations regarding the availability of software are inconsistent. We argue that, with some exceptions, anything less than the release of source programs is intolerable for results that depend on computation. The vagaries of hardware, software and natural language will always ensure that exact reproducibility remains uncertain, but withholding code increases the chances that efforts to reproduce results will fail.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ince, Darrel C -- Hatton, Leslie -- Graham-Cumming, John -- England -- Nature. 2012 Feb 22;482(7386):485-8. doi: 10.1038/nature10836.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computing Open University, Walton Hall, Milton Keynes MK7 6AA, UK. d.c.ince@open.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22358837" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Editorial Policies ; *Information Dissemination ; Intellectual Property ; Periodicals as Topic/standards ; Publishing/*standards ; Reproducibility of Results ; Research/*standards ; Research Design ; *Software
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  • 10
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    Nature Publishing Group (NPG)
    Publication Date: 2012-12-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bourzac, Katherine -- England -- Nature. 2012 Dec 6;492(7427):S18-20. doi: 10.1038/492S18a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23222670" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Aging/*drug effects/genetics/*physiology ; Animal Diseases/epidemiology/genetics/prevention & control ; Animals ; Biomedical Research ; *Caloric Restriction ; Cardiovascular Diseases/prevention & control ; Female ; Gene Expression Profiling ; Geriatrics/methods ; Humans ; Longevity/*drug effects/genetics/*physiology ; Macaca mulatta/physiology ; Male ; Mice ; Models, Animal ; Neoplasms/prevention & control ; Oligonucleotide Array Sequence Analysis ; Reproducibility of Results ; Sirolimus/adverse effects/analogs & derivatives/immunology/*pharmacology ; Sirtuins/deficiency/genetics/metabolism ; Somatomedins/genetics/metabolism ; Stilbenes/pharmacology ; TOR Serine-Threonine Kinases/metabolism
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  • 11
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    Nature Publishing Group (NPG)
    Publication Date: 2012-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tollefson, Jeff -- England -- Nature. 2012 May 9;485(7397):164-6. doi: 10.1038/485164a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575940" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; Aerosols/*analysis ; Air Pollution/statistics & numerical data ; Arctic Regions ; Atlantic Ocean ; Atmosphere/analysis/chemistry ; Color ; Geography ; Global Warming/*statistics & numerical data ; Human Activities ; Ice Cover ; Meteorological Concepts ; *Meteorology ; Models, Theoretical ; Reproducibility of Results ; Seawater ; Sunlight ; Temperature ; Uncertainty
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 12
    Publication Date: 2012-12-14
    Description: The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653568/" 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/PMC3653568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Besnard, Jeremy -- Ruda, Gian Filippo -- Setola, Vincent -- Abecassis, Keren -- Rodriguiz, Ramona M -- Huang, Xi-Ping -- Norval, Suzanne -- Sassano, Maria F -- Shin, Antony I -- Webster, Lauren A -- Simeons, Frederick R C -- Stojanovski, Laste -- Prat, Annik -- Seidah, Nabil G -- Constam, Daniel B -- Bickerton, G Richard -- Read, Kevin D -- Wetsel, William C -- Gilbert, Ian H -- Roth, Bryan L -- Hopkins, Andrew L -- 083481/Wellcome Trust/United Kingdom -- BB/FOF/PF/15/09/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/J010510/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MH082441/MH/NIMH NIH HHS/ -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- WT 083481/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Dec 13;492(7428):215-20. doi: 10.1038/nature11691.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Automation ; Drug Delivery Systems ; *Drug Design ; Female ; *Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Models, Theoretical ; Pharmacological Phenomena ; Reproducibility of Results
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  • 13
    Publication Date: 2012-10-02
    Description: The genome-wide identification of pairs of interacting proteins is an important step in the elucidation of cell regulatory mechanisms. Much of our present knowledge derives from high-throughput techniques such as the yeast two-hybrid assay and affinity purification, as well as from manual curation of experiments on individual systems. A variety of computational approaches based, for example, on sequence homology, gene co-expression and phylogenetic profiles, have also been developed for the genome-wide inference of protein-protein interactions (PPIs). Yet comparative studies suggest that the development of accurate and complete repertoires of PPIs is still in its early stages. Here we show that three-dimensional structural information can be used to predict PPIs with an accuracy and coverage that are superior to predictions based on non-structural evidence. Moreover, an algorithm, termed PrePPI, which combines structural information with other functional clues, is comparable in accuracy to high-throughput experiments, yielding over 30,000 high-confidence interactions for yeast and over 300,000 for human. Experimental tests of a number of predictions demonstrate the ability of the PrePPI algorithm to identify unexpected PPIs of considerable biological interest. The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482288/" 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/PMC3482288/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Qiangfeng Cliff -- Petrey, Donald -- Deng, Lei -- Qiang, Li -- Shi, Yu -- Thu, Chan Aye -- Bisikirska, Brygida -- Lefebvre, Celine -- Accili, Domenico -- Hunter, Tony -- Maniatis, Tom -- Califano, Andrea -- Honig, Barry -- CA082683/CA/NCI NIH HHS/ -- CA121852/CA/NCI NIH HHS/ -- DK057539/DK/NIDDK NIH HHS/ -- GM030518/GM/NIGMS NIH HHS/ -- GM094597/GM/NIGMS NIH HHS/ -- R01 CA082683/CA/NCI NIH HHS/ -- R01 DK057539/DK/NIDDK NIH HHS/ -- R01 GM030518/GM/NIGMS NIH HHS/ -- R01 NS043915/NS/NINDS NIH HHS/ -- R01NS043915/NS/NINDS NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 GM094597/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Oct 25;490(7421):556-60. doi: 10.1038/nature11503. Epub 2012 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023127" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Animals ; Bayes Theorem ; Brain/metabolism ; Cadherins/metabolism ; High-Throughput Screening Assays ; Humans ; Matrix Attachment Region Binding Proteins/metabolism ; Mice ; Models, Molecular ; PPAR gamma/metabolism ; Phylogeny ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping/*methods ; *Protein Interaction Maps ; Protein Kinases/chemistry/metabolism ; Proteins/*chemistry/*metabolism ; Proteome/chemistry/metabolism ; Proteomics/*methods ; ROC Curve ; Reproducibility of Results ; Saccharomyces cerevisiae/chemistry/metabolism ; Suppressor of Cytokine Signaling Proteins/metabolism ; Transcription Factors/metabolism
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  • 14
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    Nature Publishing Group (NPG)
    Publication Date: 2012-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Mar 28;483(7391):509. doi: 10.1038/483509a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460859" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Science Disciplines/standards ; Humans ; Periodicals as Topic/standards ; Quality Control ; Reproducibility of Results ; Research/*standards ; Research Design/standards/*statistics & numerical data ; Research Personnel/*standards ; Treatment Failure
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  • 15
    Publication Date: 2012-04-13
    Description: Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863681/" 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/PMC3863681/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shah, Sohrab P -- Roth, Andrew -- Goya, Rodrigo -- Oloumi, Arusha -- Ha, Gavin -- Zhao, Yongjun -- Turashvili, Gulisa -- Ding, Jiarui -- Tse, Kane -- Haffari, Gholamreza -- Bashashati, Ali -- Prentice, Leah M -- Khattra, Jaswinder -- Burleigh, Angela -- Yap, Damian -- Bernard, Virginie -- McPherson, Andrew -- Shumansky, Karey -- Crisan, Anamaria -- Giuliany, Ryan -- Heravi-Moussavi, Alireza -- Rosner, Jamie -- Lai, Daniel -- Birol, Inanc -- Varhol, Richard -- Tam, Angela -- Dhalla, Noreen -- Zeng, Thomas -- Ma, Kevin -- Chan, Simon K -- Griffith, Malachi -- Moradian, Annie -- Cheng, S-W Grace -- Morin, Gregg B -- Watson, Peter -- Gelmon, Karen -- Chia, Stephen -- Chin, Suet-Feung -- Curtis, Christina -- Rueda, Oscar M -- Pharoah, Paul D -- Damaraju, Sambasivarao -- Mackey, John -- Hoon, Kelly -- Harkins, Timothy -- Tadigotla, Vasisht -- Sigaroudinia, Mahvash -- Gascard, Philippe -- Tlsty, Thea -- Costello, Joseph F -- Meyer, Irmtraud M -- Eaves, Connie J -- Wasserman, Wyeth W -- Jones, Steven -- Huntsman, David -- Hirst, Martin -- Caldas, Carlos -- Marra, Marco A -- Aparicio, Samuel -- 5U01ES017154-02/ES/NIEHS NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- R01GM084875/GM/NIGMS NIH HHS/ -- Cancer Research UK/United Kingdom -- England -- Nature. 2012 Apr 4;486(7403):395-9. doi: 10.1038/nature10933.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. sshah@bccrc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22495314" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Breast Neoplasms/diagnosis/*genetics/*pathology ; Clone Cells/metabolism/pathology ; DNA Copy Number Variations/genetics ; DNA Mutational Analysis ; Disease Progression ; *Evolution, Molecular ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; INDEL Mutation/genetics ; Mutation/*genetics ; Point Mutation/genetics ; Precision Medicine ; Reproducibility of Results ; Sequence Analysis, RNA
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  • 16
    Publication Date: 2012-02-10
    Description: Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin-beta2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-beta2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874809/" 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/PMC3874809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsushita, Hirokazu -- Vesely, Matthew D -- Koboldt, Daniel C -- Rickert, Charles G -- Uppaluri, Ravindra -- Magrini, Vincent J -- Arthur, Cora D -- White, J Michael -- Chen, Yee-Shiuan -- Shea, Lauren K -- Hundal, Jasreet -- Wendl, Michael C -- Demeter, Ryan -- Wylie, Todd -- Allison, James P -- Smyth, Mark J -- Old, Lloyd J -- Mardis, Elaine R -- Schreiber, Robert D -- R01 CA043059/CA/NCI NIH HHS/ -- U01 CA141541/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Feb 8;482(7385):400-4. doi: 10.1038/nature10755.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22318521" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Carrier Proteins/genetics/immunology ; DNA-Binding Proteins/deficiency/genetics ; Exome/*genetics/*immunology ; Histocompatibility Antigens Class I/immunology ; Humans ; Immunologic Surveillance/*immunology ; Male ; Methylcholanthrene ; Mice ; Microfilament Proteins/genetics/immunology ; Models, Immunological ; Neoplasms/chemically induced/*genetics/*immunology/pathology ; Reproducibility of Results ; Sarcoma/chemically induced/genetics/immunology/pathology ; T-Lymphocytes/*immunology
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  • 17
    Publication Date: 2012-05-19
    Description: The opioid receptor family comprises three members, the micro-, delta- and kappa-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The delta-opioid receptor (delta-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the micro-OR and kappa-OR have recently been solved. Here we report the crystal structure of the mouse delta-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the micro-OR and kappa-OR, the delta-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the delta-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523198/" 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/PMC3523198/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Granier, Sebastien -- Manglik, Aashish -- Kruse, Andrew C -- Kobilka, Tong Sun -- Thian, Foon Sun -- Weis, William I -- Kobilka, Brian K -- DA031418/DA/NIDA NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- R01 GM083118/GM/NIGMS NIH HHS/ -- R01 NS028471/NS/NINDS NIH HHS/ -- R21 DA031418/DA/NIDA NIH HHS/ -- England -- Nature. 2012 May 16;485(7398):400-4. doi: 10.1038/nature11111.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA. granier@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22596164" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Naltrexone/*analogs & derivatives/chemistry/metabolism/pharmacology ; Protein Structure, Tertiary ; Receptors, Opioid, delta/antagonists & inhibitors/*chemistry/metabolism ; Reproducibility of Results ; Structure-Activity Relationship ; Substrate Specificity
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  • 18
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    Nature Publishing Group (NPG)
    Publication Date: 2012-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maxmen, Amy -- England -- Nature. 2012 Sep 20;489(7416):349-50. doi: 10.1038/489349a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22996526" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Kidney/pathology/virology ; Kidney Diseases/*etiology/pathology/prevention & control/*virology ; Models, Biological ; RNA, Viral/urine ; Reproducibility of Results ; United States/epidemiology ; West Nile Fever/*complications/epidemiology/therapy ; West Nile virus/genetics/isolation & purification/*pathogenicity
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  • 19
    Publication Date: 2012-07-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, James A -- Eijkholt, Marleen -- Illes, Judy -- England -- Nature. 2012 Jul 25;487(7408):432. doi: 10.1038/487432a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22836987" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*ethics/methods/*standards ; *Ethics, Research ; Guidelines as Topic ; Publishing/*standards/trends ; Reproducibility of Results
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  • 20
    Publication Date: 2012-09-22
    Description: Cooperation is central to human social behaviour. However, choosing to cooperate requires individuals to incur a personal cost to benefit others. Here we explore the cognitive basis of cooperative decision-making in humans using a dual-process framework. We ask whether people are predisposed towards selfishness, behaving cooperatively only through active self-control; or whether they are intuitively cooperative, with reflection and prospective reasoning favouring 'rational' self-interest. To investigate this issue, we perform ten studies using economic games. We find that across a range of experimental designs, subjects who reach their decisions more quickly are more cooperative. Furthermore, forcing subjects to decide quickly increases contributions, whereas instructing them to reflect and forcing them to decide slowly decreases contributions. Finally, an induction that primes subjects to trust their intuitions increases contributions compared with an induction that promotes greater reflection. To explain these results, we propose that cooperation is intuitive because cooperative heuristics are developed in daily life where cooperation is typically advantageous. We then validate predictions generated by this proposed mechanism. Our results provide convergent evidence that intuition supports cooperation in social dilemmas, and that reflection can undermine these cooperative impulses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rand, David G -- Greene, Joshua D -- Nowak, Martin A -- England -- Nature. 2012 Sep 20;489(7416):427-30. doi: 10.1038/nature11467.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA. drand@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22996558" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Cooperative Behavior ; Cost-Benefit Analysis ; *Decision Making ; *Ego ; Female ; *Game Theory ; *Gift Giving ; Humans ; *Impulsive Behavior ; *Intuition ; Male ; *Models, Psychological ; Reproducibility of Results ; Time Factors ; Young Adult
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  • 21
    Publication Date: 2012-05-25
    Description: Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wolkovich, E M -- Cook, B I -- Allen, J M -- Crimmins, T M -- Betancourt, J L -- Travers, S E -- Pau, S -- Regetz, J -- Davies, T J -- Kraft, N J B -- Ault, T R -- Bolmgren, K -- Mazer, S J -- McCabe, G J -- McGill, B J -- Parmesan, C -- Salamin, N -- Schwartz, M D -- Cleland, E E -- England -- Nature. 2012 May 2;485(7399):494-7. doi: 10.1038/nature11014.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive 0116, La Jolla, California 92093, USA. wolkovich@biodiversity.ubc.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22622576" target="_blank"〉PubMed〈/a〉
    Keywords: Artifacts ; Ecosystem ; Flowers/growth & development/physiology ; *Global Warming ; *Models, Biological ; *Periodicity ; Plant Development ; Plant Leaves/growth & development/physiology ; *Plant Physiological Phenomena ; Plants/classification ; Reproducibility of Results ; Soil/chemistry ; Temperature ; Time Factors ; *Uncertainty
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  • 22
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    Nature Publishing Group (NPG)
    Publication Date: 2012-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Monya -- England -- Nature. 2012 Aug 2;488(7409):13-4. doi: 10.1038/488013a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859177" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Neoplasms/drug therapy/pathology ; Cell Tracking/*methods ; Glioblastoma/drug therapy/pathology ; Intestinal Neoplasms/drug therapy/pathology ; Mice ; Neoplastic Stem Cells/*cytology/drug effects/*pathology ; Reproducibility of Results ; Skin Neoplasms/drug therapy/pathology
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  • 23
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    Nature Publishing Group (NPG)
    Publication Date: 2012-05-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yong, Ed -- England -- Nature. 2012 May 16;485(7398):298-300. doi: 10.1038/485298a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22596136" target="_blank"〉PubMed〈/a〉
    Keywords: Bias (Epidemiology) ; Humans ; Psychology/*standards ; Publishing/standards ; Reproducibility of Results ; Scientific Misconduct/statistics & numerical data
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  • 24
    Publication Date: 2012-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2012 Mar 28;483(7391):519. doi: 10.1038/483519a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460874" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/pharmacology/therapeutic use ; Benzamides/*pharmacology/therapeutic use ; Breast Neoplasms/drug therapy ; Clinical Trials as Topic/*statistics & numerical data ; Drug Discovery/standards/*statistics & numerical data ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Hereditary Breast and Ovarian Cancer Syndrome/drug therapy/genetics ; Humans ; Ovarian Neoplasms/drug therapy ; Phthalazines/pharmacology/therapeutic use ; Piperazines/pharmacology/therapeutic use ; *Poly(ADP-ribose) Polymerase Inhibitors ; Reproducibility of Results ; Research Design/*statistics & numerical data ; Treatment Failure
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  • 25
    Publication Date: 2012-12-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heuer, Rolf-Dieter -- Rosenzweig, Cynthia -- Steltzner, Adam -- Blanpain, Cedric -- Iorns, Elizabeth -- Wang, Jun -- Handelsman, Jo -- Gowers, Tim -- De Bernardinis, Bernardo -- Fouchier, Ron -- England -- Nature. 2012 Dec 20;492(7429):335-43. doi: 10.1038/492335a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23257862" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Bioterrorism/prevention & control ; Climate Change ; Disaster Planning/history ; Earthquakes/statistics & numerical data ; Forecasting ; Genomics ; History, 20th Century ; History, 21st Century ; Humans ; Influenza A Virus, H5N1 Subtype/genetics/pathogenicity ; Influenza, Human/transmission/virology ; Mars ; Neoplastic Stem Cells/cytology ; New York City ; Physics/history ; Publishing/economics ; Reproducibility of Results ; *Research/economics/standards/statistics & numerical data ; Security Measures ; Sexism/psychology/statistics & numerical data ; Space Flight/history/instrumentation
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  • 26
    Publication Date: 2012-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Begley, C Glenn -- Ellis, Lee M -- England -- Nature. 2012 Mar 28;483(7391):531-3. doi: 10.1038/483531a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hematology and Oncology Research, Amgen, Thousand Oaks, California 91359, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22460880" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*standards ; Cell Line, Tumor ; Clinical Trials as Topic/statistics & numerical data ; Drug Evaluation, Preclinical/*standards ; Humans ; Mice ; Neoplasms/*drug therapy/genetics ; Reproducibility of Results ; Research Design/statistics & numerical data ; Survival Analysis ; Translational Medical Research/standards/*statistics & numerical data/trends ; Treatment Failure
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2012-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berglund, Jennifer -- England -- Nature. 2012 Apr 12;484(7393):S11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22509512" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal, Humanized/adverse effects ; Apitherapy ; Complementary Therapies/adverse effects/contraindications/economics/*utilization ; Controlled Clinical Trials as Topic ; Great Britain ; Humans ; Hygiene Hypothesis ; Multiple Sclerosis/immunology/*therapy ; Natalizumab ; Reproducibility of Results ; Therapy with Helminths/adverse effects/utilization ; Uncertainty ; Vitamin D/therapeutic use
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2012-07-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macarthur, Daniel -- England -- Nature. 2012 Jul 25;487(7408):427-8. doi: 10.1038/487427a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. macarthur@atgu.mgh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22836983" target="_blank"〉PubMed〈/a〉
    Keywords: Aged, 80 and over ; *Artifacts ; False Positive Reactions ; Genomics/*standards ; Humans ; Longevity/genetics ; Quality Control ; Reproducibility of Results ; *Research Design
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  • 29
    Publication Date: 2012-06-23
    Description: Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1 nM to 30 muM. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383642/" 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/PMC3383642/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lounkine, Eugen -- Keiser, Michael J -- Whitebread, Steven -- Mikhailov, Dmitri -- Hamon, Jacques -- Jenkins, Jeremy L -- Lavan, Paul -- Weber, Eckhard -- Doak, Allison K -- Cote, Serge -- Shoichet, Brian K -- Urban, Laszlo -- AG002132/AG/NIA NIH HHS/ -- GM71896/GM/NIGMS NIH HHS/ -- GM93456/GM/NIGMS NIH HHS/ -- P01 AG002132/AG/NIA NIH HHS/ -- R01 GM071896/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Jun 10;486(7403):361-7. doi: 10.1038/nature11159.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722194" target="_blank"〉PubMed〈/a〉
    Keywords: Blood Platelets/drug effects ; Chlorotrianisene/adverse effects/chemistry/pharmacology ; Cyclooxygenase 1/metabolism ; Cyclooxygenase Inhibitors/adverse effects/pharmacology ; Databases, Factual ; Drug Evaluation, Preclinical/*methods ; *Drug-Related Side Effects and Adverse Reactions ; Estrogens, Non-Steroidal/adverse effects/pharmacology ; Forecasting ; Humans ; Models, Biological ; Molecular Targeted Therapy/adverse effects ; Platelet Aggregation/drug effects ; Reproducibility of Results ; Substrate Specificity ; Toxicity Tests/*methods
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  • 30
    Publication Date: 2012-07-13
    Description: Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only approximately 100 picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 megabases. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397394/" 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/PMC3397394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peters, Brock A -- Kermani, Bahram G -- Sparks, Andrew B -- Alferov, Oleg -- Hong, Peter -- Alexeev, Andrei -- Jiang, Yuan -- Dahl, Fredrik -- Tang, Y Tom -- Haas, Juergen -- Robasky, Kimberly -- Zaranek, Alexander Wait -- Lee, Je-Hyuk -- Ball, Madeleine Price -- Peterson, Joseph E -- Perazich, Helena -- Yeung, George -- Liu, Jia -- Chen, Linsu -- Kennemer, Michael I -- Pothuraju, Kaliprasad -- Konvicka, Karel -- Tsoupko-Sitnikov, Mike -- Pant, Krishna P -- Ebert, Jessica C -- Nilsen, Geoffrey B -- Baccash, Jonathan -- Halpern, Aaron L -- Church, George M -- Drmanac, Radoje -- P50 HG005550/HG/NHGRI NIH HHS/ -- P50HG005550/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Jul 11;487(7406):190-5. doi: 10.1038/nature11236.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA. bpeters@completegenomics.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22785314" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line ; Female ; Gene Silencing ; Genetic Variation ; *Genome, Human ; Genomics/*methods ; Haplotypes ; Humans ; Mutation ; Reproducibility of Results ; Sequence Analysis, DNA/economics/*methods/standards
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  • 31
    Publication Date: 2012-11-07
    Description: Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491803/" 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/PMC3491803/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jostins, Luke -- Ripke, Stephan -- Weersma, Rinse K -- Duerr, Richard H -- McGovern, Dermot P -- Hui, Ken Y -- Lee, James C -- Schumm, L Philip -- Sharma, Yashoda -- Anderson, Carl A -- Essers, Jonah -- Mitrovic, Mitja -- Ning, Kaida -- Cleynen, Isabelle -- Theatre, Emilie -- Spain, Sarah L -- Raychaudhuri, Soumya -- Goyette, Philippe -- Wei, Zhi -- Abraham, Clara -- Achkar, Jean-Paul -- Ahmad, Tariq -- Amininejad, Leila -- Ananthakrishnan, Ashwin N -- Andersen, Vibeke -- Andrews, Jane M -- Baidoo, Leonard -- Balschun, Tobias -- Bampton, Peter A -- Bitton, Alain -- Boucher, Gabrielle -- Brand, Stephan -- Buning, Carsten -- Cohain, Ariella -- Cichon, Sven -- D'Amato, Mauro -- De Jong, Dirk -- Devaney, Kathy L -- Dubinsky, Marla -- Edwards, Cathryn -- Ellinghaus, David -- Ferguson, Lynnette R -- Franchimont, Denis -- Fransen, Karin -- Gearry, Richard -- Georges, Michel -- Gieger, Christian -- Glas, Jurgen -- Haritunians, Talin -- Hart, Ailsa -- Hawkey, Chris -- Hedl, Matija -- Hu, Xinli -- Karlsen, Tom H -- Kupcinskas, Limas -- Kugathasan, Subra -- Latiano, Anna -- Laukens, Debby -- Lawrance, Ian C -- Lees, Charlie W -- Louis, Edouard -- Mahy, Gillian -- Mansfield, John -- Morgan, Angharad R -- Mowat, Craig -- Newman, William -- Palmieri, Orazio -- Ponsioen, Cyriel Y -- Potocnik, Uros -- Prescott, Natalie J -- Regueiro, Miguel -- Rotter, Jerome I -- Russell, Richard K -- Sanderson, Jeremy D -- Sans, Miquel -- Satsangi, Jack -- Schreiber, Stefan -- Simms, Lisa A -- Sventoraityte, Jurgita -- Targan, Stephan R -- Taylor, Kent D -- Tremelling, Mark -- Verspaget, Hein W -- De Vos, Martine -- Wijmenga, Cisca -- Wilson, David C -- Winkelmann, Juliane -- Xavier, Ramnik J -- Zeissig, Sebastian -- Zhang, Bin -- Zhang, Clarence K -- Zhao, Hongyu -- International IBD Genetics Consortium (IIBDGC) -- Silverberg, Mark S -- Annese, Vito -- Hakonarson, Hakon -- Brant, Steven R -- Radford-Smith, Graham -- Mathew, Christopher G -- Rioux, John D -- Schadt, Eric E -- Daly, Mark J -- Franke, Andre -- Parkes, Miles -- Vermeire, Severine -- Barrett, Jeffrey C -- Cho, Judy H -- 068545/Z/02/Wellcome Trust/United Kingdom -- 083948/Z/07/Z/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 089120/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- AI062773/AI/NIAID NIH HHS/ -- CA141743/CA/NCI NIH HHS/ -- CZB/4/540/Chief Scientist Office/United Kingdom -- DK043351/DK/NIDDK NIH HHS/ -- DK062413/DK/NIDDK NIH HHS/ -- DK062420/DK/NIDDK NIH HHS/ -- DK062422/DK/NIDDK NIH HHS/ -- DK062423/DK/NIDDK NIH HHS/ -- DK062429/DK/NIDDK NIH HHS/ -- DK062429-S1/DK/NIDDK NIH HHS/ -- DK062431/DK/NIDDK NIH HHS/ -- DK062432/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK076984/DK/NIDDK NIH HHS/ -- DK084554/DK/NIDDK NIH HHS/ -- DK83756/DK/NIDDK NIH HHS/ -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/British Heart Foundation/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0800675/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G1002033/Medical Research Council/United Kingdom -- K23 DK097142/DK/NIDDK NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- P01 DK046763/DK/NIDDK NIH HHS/ -- P01DK046763/DK/NIDDK NIH HHS/ -- P30 DK043351/DK/NIDDK NIH HHS/ -- R01 CA141743/CA/NCI NIH HHS/ -- R01 DK055731/DK/NIDDK NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 DK062420/DK/NIDDK NIH HHS/ -- U01 DK062422/DK/NIDDK NIH HHS/ -- U01 DK062429/DK/NIDDK NIH HHS/ -- U01 DK062431/DK/NIDDK NIH HHS/ -- U01 DK062432/DK/NIDDK NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1 TR000124-01/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128233" target="_blank"〉PubMed〈/a〉
    Keywords: Colitis, Ulcerative/genetics/immunology/microbiology/physiopathology ; Crohn Disease/genetics/immunology/microbiology/physiopathology ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; *Genome-Wide Association Study ; Haplotypes/genetics ; *Host-Pathogen Interactions/genetics/immunology ; Humans ; Inflammatory Bowel Diseases/*genetics/immunology/*microbiology/physiopathology ; Mycobacterium/*immunology/pathogenicity ; Mycobacterium Infections/genetics/microbiology ; Mycobacterium tuberculosis/immunology/pathogenicity ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
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  • 32
    Publication Date: 2012-06-23
    Description: Tumour suppressor genes encode a broad class of molecules whose mutational attenuation contributes to malignant progression. In the canonical situation, the tumour suppressor is completely inactivated through a two-hit process involving a point mutation in one allele and chromosomal deletion of the other. Here, to identify tumour suppressor genes in lymphoma, we screen a short hairpin RNA library targeting genes deleted in human lymphomas. We functionally identify those genes whose suppression promotes tumorigenesis in a mouse lymphoma model. Of the nine tumour suppressors we identified, eight correspond to genes occurring in three physically linked 'clusters', suggesting that the common occurrence of large chromosomal deletions in human tumours reflects selective pressure to attenuate multiple genes. Among the new tumour suppressors are adenosylmethionine decarboxylase 1 (AMD1) and eukaryotic translation initiation factor 5A (eIF5A), two genes associated with hypusine, a unique amino acid produced as a product of polyamine metabolism through a highly conserved pathway. Through a secondary screen surveying the impact of all polyamine enzymes on tumorigenesis, we establish the polyamine-hypusine axis as a new tumour suppressor network regulating apoptosis. Unexpectedly, heterozygous deletions encompassing AMD1 and eIF5A often occur together in human lymphomas and co-suppression of both genes promotes lymphomagenesis in mice. Thus, some tumour suppressor functions can be disabled through a two-step process targeting different genes acting in the same pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530829/" 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/PMC3530829/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scuoppo, Claudio -- Miething, Cornelius -- Lindqvist, Lisa -- Reyes, Jose -- Ruse, Cristian -- Appelmann, Iris -- Yoon, Seungtai -- Krasnitz, Alexander -- Teruya-Feldstein, Julie -- Pappin, Darryl -- Pelletier, Jerry -- Lowe, Scott W -- CA087497/CA/NCI NIH HHS/ -- CA148532/CA/NCI NIH HHS/ -- MOP-106530/Canadian Institutes of Health Research/Canada -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA087497/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jul 12;487(7406):244-8. doi: 10.1038/nature11126.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722845" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Gene Deletion ; Gene Regulatory Networks ; Genetic Testing ; Humans ; Lymphoma, B-Cell/*genetics/physiopathology ; Lysine/*analogs & derivatives/chemistry ; Mice ; Mice, Inbred C57BL ; Polyamines/*chemistry ; RNA, Small Interfering/genetics/metabolism ; Reproducibility of Results ; Tumor Suppressor Proteins/*genetics
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  • 33
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    Nature Publishing Group (NPG)
    Publication Date: 2012-11-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deen, Ben -- Pelphrey, Kevin -- England -- Nature. 2012 Nov 1;491(7422):S20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, Cambridge, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23136657" target="_blank"〉PubMed〈/a〉
    Keywords: *Artifacts ; Autistic Disorder/*diagnosis/*physiopathology ; Bias (Epidemiology) ; *Brain Mapping/methods/standards ; Child ; *Head/physiology ; Humans ; Magnetic Resonance Imaging/methods/standards ; *Models, Neurological ; *Movement ; Reproducibility of Results ; Software
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  • 34
    Publication Date: 2012-08-04
    Description: The warmest global climates of the past 65 million years occurred during the early Eocene epoch (about 55 to 48 million years ago), when the Equator-to-pole temperature gradients were much smaller than today and atmospheric carbon dioxide levels were in excess of one thousand parts per million by volume. Recently the early Eocene has received considerable interest because it may provide insight into the response of Earth's climate and biosphere to the high atmospheric carbon dioxide levels that are expected in the near future as a consequence of unabated anthropogenic carbon emissions. Climatic conditions of the early Eocene 'greenhouse world', however, are poorly constrained in critical regions, particularly Antarctica. Here we present a well-dated record of early Eocene climate on Antarctica from an ocean sediment core recovered off the Wilkes Land coast of East Antarctica. The information from biotic climate proxies (pollen and spores) and independent organic geochemical climate proxies (indices based on branched tetraether lipids) yields quantitative, seasonal temperature reconstructions for the early Eocene greenhouse world on Antarctica. We show that the climate in lowland settings along the Wilkes Land coast (at a palaeolatitude of about 70 degrees south) supported the growth of highly diverse, near-tropical forests characterized by mesothermal to megathermal floral elements including palms and Bombacoideae. Notably, winters were extremely mild (warmer than 10 degrees C) and essentially frost-free despite polar darkness, which provides a critical new constraint for the validation of climate models and for understanding the response of high-latitude terrestrial ecosystems to increased carbon dioxide forcing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pross, Jorg -- Contreras, Lineth -- Bijl, Peter K -- Greenwood, David R -- Bohaty, Steven M -- Schouten, Stefan -- Bendle, James A -- Rohl, Ursula -- Tauxe, Lisa -- Raine, J Ian -- Huck, Claire E -- van de Flierdt, Tina -- Jamieson, Stewart S R -- Stickley, Catherine E -- van de Schootbrugge, Bas -- Escutia, Carlota -- Brinkhuis, Henk -- Integrated Ocean Drilling Program Expedition 318 Scientists -- England -- Nature. 2012 Aug 2;488(7409):73-7. doi: 10.1038/nature11300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Paleoenvironmental Dynamics Group, Institute of Geosciences, Goethe University Frankfurt, Altenhoferallee 1, 60438 Frankfurt, Germany. joerg.pross@em.uni-frankfurt.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22859204" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antarctic Regions ; Atmosphere/chemistry ; Carbon Dioxide/analysis ; Cell Respiration ; Ecosystem ; Geologic Sediments/chemistry ; Greenhouse Effect/*history ; History, Ancient ; Human Activities ; Lipids/analysis ; Models, Theoretical ; Photosynthesis ; Pollen ; Reproducibility of Results ; Seasons ; Spores/isolation & purification ; *Temperature ; Trees/growth & development ; *Tropical Climate
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  • 35
    Publication Date: 2012-04-17
    Description: Effective targeted cancer therapeutic development depends upon distinguishing disease-associated 'driver' mutations, which have causative roles in malignancy pathogenesis, from 'passenger' mutations, which are dispensable for cancer initiation and maintenance. Translational studies of clinically active targeted therapeutics can definitively discriminate driver from passenger lesions and provide valuable insights into human cancer biology. Activating internal tandem duplication (ITD) mutations in FLT3 (FLT3-ITD) are detected in approximately 20% of acute myeloid leukaemia (AML) patients and are associated with a poor prognosis. Abundant scientific and clinical evidence, including the lack of convincing clinical activity of early FLT3 inhibitors, suggests that FLT3-ITD probably represents a passenger lesion. Here we report point mutations at three residues within the kinase domain of FLT3-ITD that confer substantial in vitro resistance to AC220 (quizartinib), an active investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant substitutions at two of these amino acid positions was observed in eight of eight FLT3-ITD-positive AML patients with acquired resistance to AC220. Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390926/" 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/PMC3390926/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Catherine C -- Wang, Qi -- Chin, Chen-Shan -- Salerno, Sara -- Damon, Lauren E -- Levis, Mark J -- Perl, Alexander E -- Travers, Kevin J -- Wang, Susana -- Hunt, Jeremy P -- Zarrinkar, Patrick P -- Schadt, Eric E -- Kasarskis, Andrew -- Kuriyan, John -- Shah, Neil P -- P50 CA100632/CA/NCI NIH HHS/ -- P50 CA100632-06/CA/NCI NIH HHS/ -- R01 CA12886/CA/NCI NIH HHS/ -- R01 CA128864/CA/NCI NIH HHS/ -- R01 CA166616/CA/NCI NIH HHS/ -- England -- Nature. 2012 Apr 15;485(7397):260-3. doi: 10.1038/nature11016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology, University of California, San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22504184" target="_blank"〉PubMed〈/a〉
    Keywords: Benzothiazoles/pharmacology/*therapeutic use ; Cell Line, Tumor ; DNA Mutational Analysis ; Drug Resistance, Neoplasm/genetics ; Humans ; Leukemia, Myeloid, Acute/*drug therapy/*genetics/metabolism ; Models, Molecular ; Molecular Structure ; *Molecular Targeted Therapy ; Mutation/*genetics ; Phenylurea Compounds/pharmacology/*therapeutic use ; Protein Binding ; Protein Structure, Tertiary/genetics ; Recurrence ; Reproducibility of Results ; fms-Like Tyrosine Kinase 3/*antagonists & inhibitors/*genetics/metabolism
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  • 36
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    Nature Publishing Group (NPG)
    Publication Date: 2012-09-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2012 Sep 27;489(7417):484. doi: 10.1038/489484a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23018942" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Europe ; Food, Genetically Modified/*adverse effects/toxicity ; Herbicide Resistance/*genetics ; Models, Animal ; Neoplasms/*chemically induced ; Plants, Genetically Modified/*adverse effects/genetics/toxicity ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; *Research Design ; Zea mays/*genetics
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  • 37
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    Nature Publishing Group (NPG)
    Publication Date: 2012-06-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Butler, Declan -- England -- Nature. 2012 Jun 19;486(7403):301-2. doi: 10.1038/486301a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722165" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/economics/*organization & administration ; Biomedical Research/economics/manpower/*organization & administration/standards ; Cameroon ; *HIV Infections/epidemiology ; Humans ; *Leadership ; *Nobel Prize ; Reproducibility of Results
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  • 38
    Publication Date: 2012-06-23
    Description: All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428862/" 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/PMC3428862/" 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 -- Tarpey, Patrick S -- Davies, Helen -- Van Loo, Peter -- Greenman, Chris -- Wedge, David C -- Nik-Zainal, Serena -- Martin, Sancha -- Varela, Ignacio -- Bignell, Graham R -- Yates, Lucy R -- Papaemmanuil, Elli -- Beare, David -- Butler, Adam -- Cheverton, Angela -- Gamble, John -- Hinton, Jonathan -- Jia, Mingming -- Jayakumar, Alagu -- Jones, David -- Latimer, Calli -- Lau, King Wai -- McLaren, Stuart -- McBride, David J -- Menzies, Andrew -- Mudie, Laura -- Raine, Keiran -- Rad, Roland -- Chapman, Michael Spencer -- Teague, Jon -- Easton, Douglas -- Langerod, Anita -- Oslo Breast Cancer Consortium (OSBREAC) -- Lee, Ming Ta Michael -- Shen, Chen-Yang -- Tee, Benita Tan Kiat -- Huimin, Bernice Wong -- Broeks, Annegien -- Vargas, Ana Cristina -- Turashvili, Gulisa -- Martens, John -- Fatima, Aquila -- Miron, Penelope -- Chin, Suet-Feung -- Thomas, Gilles -- Boyault, Sandrine -- Mariani, Odette -- Lakhani, Sunil R -- van de Vijver, Marc -- van 't Veer, Laura -- Foekens, John -- Desmedt, Christine -- Sotiriou, Christos -- Tutt, Andrew -- Caldas, Carlos -- Reis-Filho, Jorge S -- Aparicio, Samuel A J R -- Salomon, Anne Vincent -- Borresen-Dale, Anne-Lise -- Richardson, Andrea L -- Campbell, Peter J -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- 10118/Cancer Research UK/United Kingdom -- CA089393/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- WT088340MA/Wellcome Trust/United Kingdom -- Cancer Research UK/United Kingdom -- Chief Scientist Office/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2012 May 16;486(7403):400-4. doi: 10.1038/nature11017.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722201" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Breast Neoplasms/classification/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; Cytosine/metabolism ; DNA Mutational Analysis ; Female ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mutagenesis/*genetics ; Mutation/*genetics ; Neoplasm Grading ; Oncogenes/*genetics ; Reproducibility of Results ; Signal Transduction/genetics
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  • 39
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    Nature Publishing Group (NPG)
    Publication Date: 2012-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reich, Eugenie Samuel -- England -- Nature. 2012 Sep 13;489(7415):189-90. doi: 10.1038/489189a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22972273" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cognition/physiology ; Haplorhini ; Humans ; Massachusetts ; Psychology/*ethics ; Reproducibility of Results ; Research Design ; Research Personnel/*ethics/standards ; Scientific Misconduct/*legislation & jurisprudence
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  • 40
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    Nature Publishing Group (NPG)
    Publication Date: 2012-04-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, Jocelyn -- England -- Nature. 2012 Apr 12;484(7393):S9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22509510" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal, Humanized/pharmacology ; *Disease Models, Animal ; *Drug Evaluation, Preclinical ; Encephalomyelitis, Autoimmune, Experimental/*drug ; therapy/etiology/immunology/physiopathology ; Genetic Predisposition to Disease ; Humans ; Mice ; Multiple Sclerosis/*drug therapy/genetics/immunology/*physiopathology ; Myelin Sheath/immunology ; Natalizumab ; Rats ; Reproducibility of Results ; Species Specificity ; Zebrafish/growth & development
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2012-12-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Nov 29;491(7426):637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23198300" target="_blank"〉PubMed〈/a〉
    Keywords: *Breast Neoplasms/etiology/immunology/mortality/prevention & control ; Cancer Vaccines/immunology/therapeutic use ; Female ; *Goals ; Humans ; Neoplasm Metastasis/immunology/prevention & control ; Papillomavirus Vaccines/immunology/supply & distribution ; Patient Advocacy/economics/*psychology ; *Public Opinion ; Reproducibility of Results ; Time Factors ; Trust/*psychology
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  • 42
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    Nature Publishing Group (NPG)
    Publication Date: 2012-11-30
    Description: Many palaeoclimate studies have quantified pre-anthropogenic climate change to calculate climate sensitivity (equilibrium temperature change in response to radiative forcing change), but a lack of consistent methodologies produces a wide range of estimates and hinders comparability of results. Here we present a stricter approach, to improve intercomparison of palaeoclimate sensitivity estimates in a manner compatible with equilibrium projections for future climate change. Over the past 65 million years, this reveals a climate sensitivity (in K W(-1) m(2)) of 0.3-1.9 or 0.6-1.3 at 95% or 68% probability, respectively. The latter implies a warming of 2.2-4.8 K per doubling of atmospheric CO(2), which agrees with IPCC estimates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉PALAEOSENS Project Members -- England -- Nature. 2012 Nov 29;491(7426):683-91. doi: 10.1038/nature11574.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23192145" target="_blank"〉PubMed〈/a〉
    Keywords: Calibration ; Carbon Dioxide/analysis ; *Climate ; Environmental Policy ; Feedback ; Global Warming/history/statistics & numerical data ; History, Ancient ; *Models, Theoretical ; Probability ; Reproducibility of Results ; *Temperature ; Time Factors
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  • 43
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    Nature Publishing Group (NPG)
    Publication Date: 2012-08-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lazcano, Antonio -- Hand, Kevin P -- England -- Nature. 2012 Aug 9;488(7410):160-1. doi: 10.1038/488160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22874956" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Evolution ; *Exobiology/trends ; Extraterrestrial Environment/*chemistry ; Mars ; Origin of Life ; Reproducibility of Results ; Solar System/*chemistry ; *Space Flight/trends ; United States ; United States National Aeronautics and Space Administration
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2012-11-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 Nov 1;491(7422):7-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23136647" target="_blank"〉PubMed〈/a〉
    Keywords: *Induced Pluripotent Stem Cells ; Japan ; Journalism/*standards ; Nobel Prize ; Reproducibility of Results ; Research Personnel/*ethics/standards ; *Scientific Misconduct ; Whistleblowing/psychology
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  • 45
    Publication Date: 2012-07-27
    Description: The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve 'health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laurance, William F -- Useche, D Carolina -- Rendeiro, Julio -- Kalka, Margareta -- Bradshaw, Corey J A -- Sloan, Sean P -- Laurance, Susan G -- Campbell, Mason -- Abernethy, Kate -- Alvarez, Patricia -- Arroyo-Rodriguez, Victor -- Ashton, Peter -- Benitez-Malvido, Julieta -- Blom, Allard -- Bobo, Kadiri S -- Cannon, Charles H -- Cao, Min -- Carroll, Richard -- Chapman, Colin -- Coates, Rosamond -- Cords, Marina -- Danielsen, Finn -- De Dijn, Bart -- Dinerstein, Eric -- Donnelly, Maureen A -- Edwards, David -- Edwards, Felicity -- Farwig, Nina -- Fashing, Peter -- Forget, Pierre-Michel -- Foster, Mercedes -- Gale, George -- Harris, David -- Harrison, Rhett -- Hart, John -- Karpanty, Sarah -- Kress, W John -- Krishnaswamy, Jagdish -- Logsdon, Willis -- Lovett, Jon -- Magnusson, William -- Maisels, Fiona -- Marshall, Andrew R -- McClearn, Deedra -- Mudappa, Divya -- Nielsen, Martin R -- Pearson, Richard -- Pitman, Nigel -- van der Ploeg, Jan -- Plumptre, Andrew -- Poulsen, John -- Quesada, Mauricio -- Rainey, Hugo -- Robinson, Douglas -- Roetgers, Christiane -- Rovero, Francesco -- Scatena, Frederick -- Schulze, Christian -- Sheil, Douglas -- Struhsaker, Thomas -- Terborgh, John -- Thomas, Duncan -- Timm, Robert -- Urbina-Cardona, J Nicolas -- Vasudevan, Karthikeyan -- Wright, S Joseph -- Arias-G, Juan Carlos -- Arroyo, Luzmila -- Ashton, Mark -- Auzel, Philippe -- Babaasa, Dennis -- Babweteera, Fred -- Baker, Patrick -- Banki, Olaf -- Bass, Margot -- Bila-Isia, Inogwabini -- Blake, Stephen -- Brockelman, Warren -- Brokaw, Nicholas -- Bruhl, Carsten A -- Bunyavejchewin, Sarayudh -- Chao, Jung-Tai -- Chave, Jerome -- Chellam, Ravi -- Clark, Connie J -- Clavijo, Jose -- Congdon, Robert -- Corlett, Richard -- Dattaraja, H S -- Dave, Chittaranjan -- Davies, Glyn -- Beisiegel, Beatriz de Mello -- da Silva, Rosa de Nazare Paes -- Di Fiore, Anthony -- Diesmos, Arvin -- Dirzo, Rodolfo -- Doran-Sheehy, Diane -- Eaton, Mitchell -- Emmons, Louise -- Estrada, Alejandro -- Ewango, Corneille -- Fedigan, Linda -- Feer, Francois -- Fruth, Barbara -- Willis, Jacalyn Giacalone -- Goodale, Uromi -- Goodman, Steven -- Guix, Juan C -- Guthiga, Paul -- Haber, William -- Hamer, Keith -- Herbinger, Ilka -- Hill, Jane -- Huang, Zhongliang -- Sun, I Fang -- Ickes, Kalan -- Itoh, Akira -- Ivanauskas, Natalia -- Jackes, Betsy -- Janovec, John -- Janzen, Daniel -- Jiangming, Mo -- Jin, Chen -- Jones, Trevor -- Justiniano, Hermes -- Kalko, Elisabeth -- Kasangaki, Aventino -- Killeen, Timothy -- King, Hen-biau -- Klop, Erik -- Knott, Cheryl -- Kone, Inza -- Kudavidanage, Enoka -- Ribeiro, Jose Lahoz da Silva -- Lattke, John -- Laval, Richard -- Lawton, Robert -- Leal, Miguel -- Leighton, Mark -- Lentino, Miguel -- Leonel, Cristiane -- Lindsell, Jeremy -- Ling-Ling, Lee -- Linsenmair, K Eduard -- Losos, Elizabeth -- Lugo, Ariel -- Lwanga, Jeremiah -- Mack, Andrew L -- Martins, Marlucia -- McGraw, W Scott -- McNab, Roan -- Montag, Luciano -- Thompson, Jo Myers -- Nabe-Nielsen, Jacob -- Nakagawa, Michiko -- Nepal, Sanjay -- Norconk, Marilyn -- Novotny, Vojtech -- O'Donnell, Sean -- Opiang, Muse -- Ouboter, Paul -- Parker, Kenneth -- Parthasarathy, N -- Pisciotta, Katia -- Prawiradilaga, Dewi -- Pringle, Catherine -- Rajathurai, Subaraj -- Reichard, Ulrich -- Reinartz, Gay -- Renton, Katherine -- Reynolds, Glen -- Reynolds, Vernon -- Riley, Erin -- Rodel, Mark-Oliver -- Rothman, Jessica -- Round, Philip -- Sakai, Shoko -- Sanaiotti, Tania -- Savini, Tommaso -- Schaab, Gertrud -- Seidensticker, John -- Siaka, Alhaji -- Silman, Miles R -- Smith, Thomas B -- de Almeida, Samuel Soares -- Sodhi, Navjot -- Stanford, Craig -- Stewart, Kristine -- Stokes, Emma -- Stoner, Kathryn E -- Sukumar, Raman -- Surbeck, Martin -- Tobler, Mathias -- Tscharntke, Teja -- Turkalo, Andrea -- Umapathy, Govindaswamy -- van Weerd, Merlijn -- Rivera, Jorge Vega -- Venkataraman, Meena -- Venn, Linda -- Verea, Carlos -- de Castilho, Carolina Volkmer -- Waltert, Matthias -- Wang, Benjamin -- Watts, David -- Weber, William -- West, Paige -- Whitacre, David -- Whitney, Ken -- Wilkie, David -- Williams, Stephen -- Wright, Debra D -- Wright, Patricia -- Xiankai, Lu -- Yonzon, Pralad -- Zamzani, Franky -- England -- Nature. 2012 Sep 13;489(7415):290-4. doi: 10.1038/nature11318.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Tropical Environmental and Sustainability Science and School of Marine and Tropical Biology, James Cook University, Cairns, Queensland 4878, Australia. bill.laurance@jcu.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22832582" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/statistics & numerical data ; Animals ; *Biodiversity ; Conservation of Natural Resources/*statistics & numerical data ; Data Collection ; Ecology/statistics & numerical data ; Endangered Species/*statistics & numerical data ; Environmental Pollution/adverse effects/statistics & numerical data ; Fires/statistics & numerical data ; Forestry/statistics & numerical data ; Interviews as Topic ; Mining/statistics & numerical data ; Population Growth ; Rain ; Reproducibility of Results ; Research Personnel ; Surveys and Questionnaires ; Temperature ; Trees/*physiology ; *Tropical Climate
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  • 46
    Publication Date: 2012-09-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frische, Sebastian -- England -- Nature. 2012 Sep 27;489(7417):475. doi: 10.1038/489475a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Aarhus, Denmark. sfri@ana.au.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23018928" target="_blank"〉PubMed〈/a〉
    Keywords: Authorship/*standards ; *Databases, Factual ; *Disclosure ; Internet ; Job Application ; Reproducibility of Results ; *Research Personnel
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  • 47
    Publication Date: 2012-04-13
    Description: It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected beta-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350576/" 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/PMC3350576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Roak, Brian J -- Vives, Laura -- Girirajan, Santhosh -- Karakoc, Emre -- Krumm, Niklas -- Coe, Bradley P -- Levy, Roie -- Ko, Arthur -- Lee, Choli -- Smith, Joshua D -- Turner, Emily H -- Stanaway, Ian B -- Vernot, Benjamin -- Malig, Maika -- Baker, Carl -- Reilly, Beau -- Akey, Joshua M -- Borenstein, Elhanan -- Rieder, Mark J -- Nickerson, Deborah A -- Bernier, Raphael -- Shendure, Jay -- Eichler, Evan E -- HD065285/HD/NICHD NIH HHS/ -- HHSN273200800010C/PHS HHS/ -- HL 094976/HL/NHLBI NIH HHS/ -- HL 1029230/HL/NHLBI NIH HHS/ -- HL 102924/HL/NHLBI NIH HHS/ -- HL102926/HL/NHLBI NIH HHS/ -- R01 HD065285/HD/NICHD NIH HHS/ -- R01 HD065285-02/HD/NICHD NIH HHS/ -- R01 HL094976/HL/NHLBI NIH HHS/ -- RC2 HL102923/HL/NHLBI NIH HHS/ -- RC2 HL102926/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Apr 4;485(7397):246-50. doi: 10.1038/nature10989.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22495309" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/*genetics ; DNA-Binding Proteins/genetics ; Exome/*genetics ; Exons/*genetics ; GPI-Linked Proteins/genetics ; Genetic Predisposition to Disease/genetics ; Humans ; Laminin/genetics ; NAV1.1 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins/genetics ; Parents ; Point Mutation/*genetics ; Protein Interaction Maps/*genetics ; Receptors, N-Methyl-D-Aspartate/genetics ; Reproducibility of Results ; Siblings ; Signal Transduction ; Sodium Channels/genetics ; Stochastic Processes ; Transcription Factors/genetics ; Tumor Suppressor Protein p53/metabolism ; beta Catenin/metabolism
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    Publication Date: 2012-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2012 May 9;485(7397):147. doi: 10.1038/485147a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575920" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/epidemiology ; Child ; Child Mortality ; Cost-Benefit Analysis ; *Disclosure ; Female ; Humans ; *International Cooperation ; Investments/trends ; Poverty/economics/*prevention & control ; Reproducibility of Results ; Rural Health/economics/*statistics & numerical data ; Rural Population/statistics & numerical data ; *Statistics as Topic/standards ; Trust
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  • 49
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    Publication Date: 2012-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, Natasha -- England -- Nature. 2012 Sep 6;489(7414):14-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22962698" target="_blank"〉PubMed〈/a〉
    Keywords: Conservation of Natural Resources/*statistics & numerical data ; Forestry/*statistics & numerical data ; India ; Reproducibility of Results ; Satellite Communications ; Trees/*growth & development
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  • 50
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    Nature Publishing Group (NPG)
    Publication Date: 2012-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2012 Apr 11;484(7393):149-50. doi: 10.1038/484149a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22498601" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/therapy ; China ; Controlled Clinical Trials as Topic ; Humans ; Parkinson Disease/therapy ; *Patient Advocacy/legislation & jurisprudence ; Reproducibility of Results ; Stem Cell Transplantation/adverse effects/economics/*ethics/*legislation & ; jurisprudence
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  • 51
    Publication Date: 2012-09-14
    Description: The principle that 'popularity is attractive' underlies preferential attachment, which is a common explanation for the emergence of scaling in growing networks. If new connections are made preferentially to more popular nodes, then the resulting distribution of the number of connections possessed by nodes follows power laws, as observed in many real networks. Preferential attachment has been directly validated for some real networks (including the Internet), and can be a consequence of different underlying processes based on node fitness, ranking, optimization, random walks or duplication. Here we show that popularity is just one dimension of attractiveness; another dimension is similarity. We develop a framework in which new connections optimize certain trade-offs between popularity and similarity, instead of simply preferring popular nodes. The framework has a geometric interpretation in which popularity preference emerges from local optimization. As opposed to preferential attachment, our optimization framework accurately describes the large-scale evolution of technological (the Internet), social (trust relationships between people) and biological (Escherichia coli metabolic) networks, predicting the probability of new links with high precision. The framework that we have developed can thus be used for predicting new links in evolving networks, and provides a different perspective on preferential attachment as an emergent phenomenon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Papadopoulos, Fragkiskos -- Kitsak, Maksim -- Serrano, M Angeles -- Boguna, Marian -- Krioukov, Dmitri -- England -- Nature. 2012 Sep 27;489(7417):537-40. doi: 10.1038/nature11459. Epub 2012 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Computer Engineering and Informatics, Cyprus University of Technology, 33 Saripolou Street, 3036 Limassol, Cyprus. f.papadopoulos@cut.ac.cy〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22972194" target="_blank"〉PubMed〈/a〉
    Keywords: Escherichia coli/metabolism ; Humans ; Internet/*statistics & numerical data ; *Metabolic Networks and Pathways ; Models, Biological ; *Models, Theoretical ; Probability ; Reproducibility of Results ; *Social Networking ; Trust
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 52
    Publication Date: 2012-07-20
    Description: Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pichlmair, Andreas -- Kandasamy, Kumaran -- Alvisi, Gualtiero -- Mulhern, Orla -- Sacco, Roberto -- Habjan, Matthias -- Binder, Marco -- Stefanovic, Adrijana -- Eberle, Carol-Ann -- Goncalves, Adriana -- Burckstummer, Tilmann -- Muller, Andre C -- Fauster, Astrid -- Holze, Cathleen -- Lindsten, Kristina -- Goodbourn, Stephen -- Kochs, Georg -- Weber, Friedemann -- Bartenschlager, Ralf -- Bowie, Andrew G -- Bennett, Keiryn L -- Colinge, Jacques -- Superti-Furga, Giulio -- England -- Nature. 2012 Jul 26;487(7408):486-90. doi: 10.1038/nature11289.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CeMMResearch Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22810585" target="_blank"〉PubMed〈/a〉
    Keywords: Endopeptidases/metabolism ; HEK293 Cells ; Heterogeneous-Nuclear Ribonucleoprotein U/metabolism ; Host-Pathogen Interactions/*immunology/physiology ; Humans ; Immunity, Innate/immunology ; Mass Spectrometry ; Open Reading Frames/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Reproducibility of Results ; Signal Transduction ; Substrate Specificity ; Viral Proteins/genetics/immunology/metabolism ; Viruses/*immunology/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2012-10-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2012 Oct 25;490(7421):466-8. doi: 10.1038/490466a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23099382" target="_blank"〉PubMed〈/a〉
    Keywords: Advertising as Topic/methods ; *Attitude ; *Biology ; Emotions/*physiology ; Empathy ; Fear ; Gene-Environment Interaction ; Genome-Wide Association Study ; Humans ; Oxytocin/analysis ; Personality/*genetics ; *Politics ; Prejudice/psychology ; Reproducibility of Results ; Twin Studies as Topic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 54
    Publication Date: 2012-11-20
    Description: Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation. To explore this issue, here we perform a whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two copy number variants (CNVs) not apparent in the fibroblasts from which the iPSC was derived. Using PCR and digital droplet PCR, we show that at least 50% of those CNVs are present as low-frequency somatic genomic variants in parental fibroblasts (that is, the fibroblasts from which each corresponding human iPSC line is derived), and are manifested in iPSC lines owing to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSCs, because most of the line-manifested CNVs reflect somatic mosaicism in the human skin. Moreover, our findings demonstrate that clonal expansion, and iPSC lines in particular, can be used as a discovery tool to reliably detect low-frequency CNVs in the tissue of origin. Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs in their genomes, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532053/" 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/PMC3532053/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abyzov, Alexej -- Mariani, Jessica -- Palejev, Dean -- Zhang, Ying -- Haney, Michael Seamus -- Tomasini, Livia -- Ferrandino, Anthony F -- Rosenberg Belmaker, Lior A -- Szekely, Anna -- Wilson, Michael -- Kocabas, Arif -- Calixto, Nathaniel E -- Grigorenko, Elena L -- Huttner, Anita -- Chawarska, Katarzyna -- Weissman, Sherman -- Urban, Alexander Eckehart -- Gerstein, Mark -- Vaccarino, Flora M -- MH087879/MH/NIMH NIH HHS/ -- MH089176/MH/NIMH NIH HHS/ -- R01 MH089176/MH/NIMH NIH HHS/ -- R33 MH087879/MH/NIMH NIH HHS/ -- RR19895/RR/NCRR NIH HHS/ -- England -- Nature. 2012 Dec 20;492(7429):438-42. doi: 10.1038/nature11629. Epub 2012 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurodevelopment and Regeneration, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160490" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation ; Cells, Cultured ; Cellular Reprogramming ; Clone Cells ; DNA Copy Number Variations/*genetics ; Fibroblasts/cytology ; Gene Expression Profiling ; Genome, Human/genetics ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Male ; *Mosaicism ; Neurons/cytology ; Polymerase Chain Reaction ; Reproducibility of Results ; Skin/cytology/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 55
    Publication Date: 2012-01-13
    Description: Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267864/" 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/PMC3267864/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Li -- Ley, Timothy J -- Larson, David E -- Miller, Christopher A -- Koboldt, Daniel C -- Welch, John S -- Ritchey, Julie K -- Young, Margaret A -- Lamprecht, Tamara -- McLellan, Michael D -- McMichael, Joshua F -- Wallis, John W -- Lu, Charles -- Shen, Dong -- Harris, Christopher C -- Dooling, David J -- Fulton, Robert S -- Fulton, Lucinda L -- Chen, Ken -- Schmidt, Heather -- Kalicki-Veizer, Joelle -- Magrini, Vincent J -- Cook, Lisa -- McGrath, Sean D -- Vickery, Tammi L -- Wendl, Michael C -- Heath, Sharon -- Watson, Mark A -- Link, Daniel C -- Tomasson, Michael H -- Shannon, William D -- Payton, Jacqueline E -- Kulkarni, Shashikant -- Westervelt, Peter -- Walter, Matthew J -- Graubert, Timothy A -- Mardis, Elaine R -- Wilson, Richard K -- DiPersio, John F -- P01 CA101937/CA/NCI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-10/HG/NHGRI NIH HHS/ -- England -- Nature. 2012 Jan 11;481(7382):506-10. doi: 10.1038/nature10738.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Institute, Washington University, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22237025" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/adverse effects/therapeutic use ; Clonal Evolution/*genetics ; Clone Cells/drug effects/metabolism/pathology ; DNA Damage/drug effects ; DNA Mutational Analysis ; Genes, Neoplasm/genetics ; Genome, Human/drug effects/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute/drug therapy/*genetics/*pathology ; Mutagenesis/drug effects/genetics ; Recurrence ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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