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  • Articles  (897)
  • History, 20th Century  (466)
  • Cell Line  (429)
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  • Articles  (897)
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  • 1
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joseph, Mathai -- Robinson, Andrew -- England -- Nature. 2014 Apr 3;508(7494):36-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24707526" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/economics/organization & administration ; Federal Government ; History, 20th Century ; History, 21st Century ; India ; Informatics ; Research Support as Topic ; Science/economics/history/*legislation & jurisprudence/*organization & ; administration
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-11-20
    Description: Emerging evidence suggests that the ribosome has a regulatory function in directing how the genome is translated in time and space. However, how this regulation is encoded in the messenger RNA sequence remains largely unknown. Here we uncover unique RNA regulons embedded in homeobox (Hox) 5' untranslated regions (UTRs) that confer ribosome-mediated control of gene expression. These structured RNA elements, resembling viral internal ribosome entry sites (IRESs), are found in subsets of Hox mRNAs. They facilitate ribosome recruitment and require the ribosomal protein RPL38 for their activity. Despite numerous layers of Hox gene regulation, these IRES elements are essential for converting Hox transcripts into proteins to pattern the mammalian body plan. This specialized mode of IRES-dependent translation is enabled by an additional regulatory element that we term the translation inhibitory element (TIE), which blocks cap-dependent translation of transcripts. Together, these data uncover a new paradigm for ribosome-mediated control of gene expression and organismal development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353651/" 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/PMC4353651/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xue, Shifeng -- Tian, Siqi -- Fujii, Kotaro -- Kladwang, Wipapat -- Das, Rhiju -- Barna, Maria -- 7DP2OD00850902/OD/NIH HHS/ -- DP2 OD008509/OD/NIH HHS/ -- R01 GM102519/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 1;517(7532):33-8. doi: 10.1038/nature14010. Epub 2014 Nov 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA [3] Tetrad Graduate Program, University of California, San Francisco, San Francisco, California 94158, USA. ; Department of Biochemistry, Stanford University, Stanford, California 94305, USA. ; 1] Department of Developmental Biology, Stanford University, Stanford, California 94305, USA [2] Department of Genetics, Stanford University, Stanford, California 94305, USA. ; 1] Department of Biochemistry, Stanford University, Stanford, California 94305, USA [2] Department of Physics, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409156" target="_blank"〉PubMed〈/a〉
    Keywords: 5' Untranslated Regions/*genetics ; Animals ; Bone and Bones/embryology/metabolism ; Cell Line ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Regulation/*genetics ; Genes, Homeobox/*genetics ; Mice ; Molecular Sequence Data ; Protein Biosynthesis/genetics ; RNA Caps/metabolism ; Regulatory Sequences, Ribonucleic Acid/*genetics ; Ribosomal Proteins/metabolism ; Ribosomes/chemistry/*metabolism ; Substrate Specificity ; Zebrafish/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-12-18
    Description: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as alpha2a- and beta1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucrot, Emmanuel -- Ferreira, Antonio P A -- Almeida-Souza, Leonardo -- Debard, Sylvain -- Vallis, Yvonne -- Howard, Gillian -- Bertot, Laetitia -- Sauvonnet, Nathalie -- McMahon, Harvey T -- U105178805/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Superieure de Cachan, 94235 Cachan, France. ; Institut Pasteur, Unite de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517094" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Cell Line ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Ligands ; Phosphatidylinositol Phosphates/metabolism ; Pseudopodia/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Interleukin-2/metabolism ; Signal Transduction ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-05-17
    Description: A switchlike response in nuclear factor-kappaB (NF-kappaB) activity implies the existence of a threshold in the NF-kappaB signaling module. We show that the CARD-containing MAGUK protein 1 (CARMA1, also called CARD11)-TAK1 (MAP3K7)-inhibitor of NF-kappaB (IkappaB) kinase-beta (IKKbeta) module is a switch mechanism for NF-kappaB activation in B cell receptor (BCR) signaling. Experimental and mathematical modeling analyses showed that IKK activity is regulated by positive feedback from IKKbeta to TAK1, generating a steep dose response to BCR stimulation. Mutation of the scaffolding protein CARMA1 at serine-578, an IKKbeta target, abrogated not only late TAK1 activity, but also the switchlike activation of NF-kappaB in single cells, suggesting that phosphorylation of this residue accounts for the feedback.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shinohara, Hisaaki -- Behar, Marcelo -- Inoue, Kentaro -- Hiroshima, Michio -- Yasuda, Tomoharu -- Nagashima, Takeshi -- Kimura, Shuhei -- Sanjo, Hideki -- Maeda, Shiori -- Yumoto, Noriko -- Ki, Sewon -- Akira, Shizuo -- Sako, Yasushi -- Hoffmann, Alexander -- Kurosaki, Tomohiro -- Okada-Hatakeyama, Mariko -- 5R01CA141722/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 May 16;344(6185):760-4. doi: 10.1126/science.1250020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ; Laboratory for Cell Signaling Dynamics, RIKEN Quantitative Biology Center (QBiC), 6-2-3, Furuedai, Suita, Osaka 565-0874, Japan. Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ; Graduate School of Engineering, Tottori University 4-101, Koyama-minami, Tottori 680-8552, Japan. ; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ; Cellular Informatics Laboratory, RIKEN, 2-1 Hirosawa, Wako 351-0198, Japan. ; Signaling Systems Laboratory, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences (QC Bio) and Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90025, USA. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Laboratory for Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp. ; Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. ahoffmann@ucla.edu kurosaki@rcai.riken.jp marikoh@rcai.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24833394" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism ; CARD Signaling Adaptor Proteins/genetics/*metabolism ; Cell Line ; Chickens ; Feedback, Physiological ; Guanylate Cyclase/genetics/*metabolism ; I-kappa B Kinase/*metabolism ; MAP Kinase Kinase Kinases/genetics/*metabolism ; Mice ; Mice, Knockout ; Mutation ; NF-kappa B/*agonists ; Phosphorylation ; Receptors, Antigen, B-Cell/genetics/*metabolism ; Serine/genetics/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popkin, Gabriel -- New York, N.Y. -- Science. 2014 Sep 26;345(6204):1552-4. doi: 10.1126/science.345.6204.1552.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25258061" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; Ecology/*history ; History, 20th Century ; History, 21st Century ; *Lakes ; Limnology/*history ; Music ; Netherlands ; Personal Autonomy
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharjee, Yudhijit -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1306-9. doi: 10.1126/science.343.6177.1306.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653017" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Evolution ; DNA, Intergenic/genetics ; Databases, Nucleic Acid ; *Genome, Human ; *Genomics ; History, 20th Century ; History, 21st Century ; Humans ; Molecular Sequence Annotation ; Mutation ; National Human Genome Research Institute (U.S.) ; Transcription Factors/metabolism ; Transcription, Genetic ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-05-24
    Description: Decisions take time if information gradually accumulates to a response threshold, but the neural mechanisms of integration and thresholding are unknown. We characterized a decision process in Drosophila that bears the behavioral signature of evidence accumulation. As stimulus contrast in trained odor discriminations decreased, reaction times increased and perceptual accuracy declined, in quantitative agreement with a drift-diffusion model. FoxP mutants took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult, low-contrast tasks. RNA interference with FoxP expression in alphabeta core Kenyon cells, or the overexpression of a potassium conductance in these neurons, recapitulated the FoxP mutant phenotype. A mushroom body subdomain whose development or function require the transcription factor FoxP thus supports the progression of a decision toward commitment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206523/" 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/PMC4206523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DasGupta, Shamik -- Ferreira, Clara Howcroft -- Miesenbock, Gero -- 090309/Wellcome Trust/United Kingdom -- G0700888/Medical Research Council/United Kingdom -- G0701225/Medical Research Council/United Kingdom -- R01 DA030601/DA/NIDA NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 May 23;344(6186):901-4. doi: 10.1126/science.1252114.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR, UK. ; Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford, OX1 3SR, UK. gero.miesenboeck@cncb.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855268" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Cell Line ; *Decision Making ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster/genetics/*physiology ; Forkhead Transcription Factors/genetics/*physiology ; Mushroom Bodies/growth & development/metabolism ; Mutation ; Neurons/physiology ; Odors ; *Psychomotor Performance ; RNA Interference ; Reaction Time/genetics/*physiology ; Smell
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-08-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goudsmit, Jaap -- New York, N.Y. -- Science. 2014 Aug 22;345(6199):881. doi: 10.1126/science.1259453.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. jaap@jaapgoudsmit.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25146275" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/blood/*history/immunology ; HIV/immunology ; HIV Antibodies/blood/*history ; History, 20th Century ; History, 21st Century ; Humans ; Netherlands
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-03-01
    Description: Epigenetic gene silencing is seen in several repeat-expansion diseases. In fragile X syndrome, the most common genetic form of mental retardation, a CGG trinucleotide-repeat expansion adjacent to the fragile X mental retardation 1 (FMR1) gene promoter results in its epigenetic silencing. Here, we show that FMR1 silencing is mediated by the FMR1 mRNA. The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5' untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA.DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357282/" 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/PMC4357282/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colak, Dilek -- Zaninovic, Nikica -- Cohen, Michael S -- Rosenwaks, Zev -- Yang, Wang-Yong -- Gerhardt, Jeannine -- Disney, Matthew D -- Jaffrey, Samie R -- R01 GM079235/GM/NIGMS NIH HHS/ -- R01 MH80420/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2014 Feb 28;343(6174):1002-5. doi: 10.1126/science.1245831.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24578575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; DNA Methylation ; Embryonic Stem Cells/metabolism ; Fragile X Mental Retardation Protein/*genetics ; Fragile X Syndrome/*genetics ; *Gene Silencing ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neurons/metabolism ; Nuclear Proteins/genetics ; Promoter Regions, Genetic/genetics ; RNA, Messenger/*genetics ; RNA, Small Interfering/genetics ; Trinucleotide Repeats/*genetics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-10-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zoback, Mary Lou -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):283. doi: 10.1126/science.1261788.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mary Lou Zoback is a consulting professor in the Department of Geophysics, Stanford University, Stanford, CA. marylouz@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324360" target="_blank"〉PubMed〈/a〉
    Keywords: California ; Disasters/*history ; Earthquakes/*history/mortality ; Haiti ; History, 20th Century ; Humans ; Rescue Work
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-05-24
    Description: This Review presents basic facts regarding the long-run evolution of income and wealth inequality in Europe and the United States. Income and wealth inequality was very high a century ago, particularly in Europe, but dropped dramatically in the first half of the 20th century. Income inequality has surged back in the United States since the 1970s so that the United States is much more unequal than Europe today. We discuss possible interpretations and lessons for the future.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Piketty, Thomas -- Saez, Emmanuel -- New York, N.Y. -- Science. 2014 May 23;344(6186):838-43. doi: 10.1126/science.1251936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Economics, Paris School of Economics, Paris, France. thomas.piketty@psemail.eu. ; Department of Economics, University of California at Berkeley, Berkeley, CA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24855258" target="_blank"〉PubMed〈/a〉
    Keywords: *Economic Development ; Europe ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Income/history/*statistics & numerical data/*trends ; Socioeconomic Factors/history ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 12
    Publication Date: 2014-06-28
    Description: Dynamin superfamily molecular motors use guanosine triphosphate (GTP) as a source of energy for membrane-remodeling events. We found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine triphosphate (ATP)-driven conversion of guanosine diphosphate (GDP), inhibited dynamin-mediated endocytosis. NM23-H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin. In vitro, NM23-H1/H2 were recruited to dynamin-induced tubules, stimulated GTP-loading on dynamin, and triggered fission in the presence of ATP and GDP. NM23-H4, a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 involved in mitochondria inner membrane fusion and increased GTP-loading on OPA1. Like OPA1 loss of function, silencing of NM23-H4 but not NM23-H1/H2 resulted in mitochondrial fragmentation, reflecting fusion defects. Thus, NDPKs interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601533/" 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/PMC4601533/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boissan, Mathieu -- Montagnac, Guillaume -- Shen, Qinfang -- Griparic, Lorena -- Guitton, Jerome -- Romao, Maryse -- Sauvonnet, Nathalie -- Lagache, Thibault -- Lascu, Ioan -- Raposo, Graca -- Desbourdes, Celine -- Schlattner, Uwe -- Lacombe, Marie-Lise -- Polo, Simona -- van der Bliek, Alexander M -- Roux, Aurelien -- Chavrier, Philippe -- 311536/European Research Council/International -- New York, N.Y. -- Science. 2014 Jun 27;344(6191):1510-5. doi: 10.1126/science.1253768.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. Universite Pierre et Marie Curie, University Paris 06, Paris, France. Saint-Antoine Research Center, INSERM UMR-S 938, Paris, France. mathieu.boissan@inserm.fr philippe.chavrier@curie.fr. ; Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. ; Department of Biological Chemistry, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA. ; Hospices Civils de Lyon, Pierre Benite, France. Universite de Lyon, Lyon, France. ; Institut Curie, Research Center, Paris, France. Structure and Membrane Compartments, CNRS UMR 144, Paris, France. ; Institut Pasteur, Unite de Biologie des Interactions Cellulaires, Paris, France. ; Quantitative Image Analysis Unit, Institut Pasteur, Paris, France. ; Institut de Biochimie et Genetique Cellulaires-CNRS, Universite Bordeaux 2, Bordeaux, France. ; Universite Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France. Inserm, U1055, Grenoble, France. ; Universite Pierre et Marie Curie, University Paris 06, Paris, France. Saint-Antoine Research Center, INSERM UMR-S 938, Paris, France. ; IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. Dipartimento di Scienze della Salute, Universita' degli Studi di Milano, Milan, Italy. ; Biochemistry Department, University of Geneva, & Swiss National Center for Competence in Research Program Chemical Biology, Geneva, Switzerland. ; Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. mathieu.boissan@inserm.fr philippe.chavrier@curie.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24970086" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Cell Line ; Cell Membrane/*metabolism ; Coated Pits, Cell-Membrane/metabolism ; Dynamins/*metabolism ; Endocytosis ; GTP Phosphohydrolases/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/*metabolism ; Humans ; Intracellular Membranes/metabolism ; Membrane Fusion ; Mitochondria/metabolism ; NM23 Nucleoside Diphosphate Kinases/genetics/*metabolism ; Nucleoside Diphosphate Kinase D/metabolism
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-07-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2014 Jul 4;345(6192):18-23. doi: 10.1126/science.345.6192.18.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24994630" target="_blank"〉PubMed〈/a〉
    Keywords: Affect/drug effects ; Clinical Trials, Phase III as Topic ; Hallucinogens/history/*therapeutic use ; History, 20th Century ; Humans ; Lysergic Acid Diethylamide/administration & dosage/history ; Psilocybine/history/*therapeutic use
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2014-03-29
    Description: The existence of BRCA1 was proven in 1990 by mapping predisposition to young-onset breast cancer in families to chromosome 17q21. Knowing that such a gene existed and approximately where it lay triggered efforts by public and private groups to clone and sequence it. The press baptized the competition "the race" and reported on it in detail for the next 4 years. BRCA1 was positionally cloned in September 1994. Twenty years later, I reflect on "the race" and its consequences for breast cancer prevention and treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, Mary-Claire -- R01 CA157744/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Mar 28;343(6178):1462-5. doi: 10.1126/science.1251900.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24675952" target="_blank"〉PubMed〈/a〉
    Keywords: BRCA1 Protein/*genetics/history ; Breast Neoplasms/*genetics/history ; Chromosome Mapping ; Chromosomes, Human, Pair 17/*genetics ; Cloning, Molecular ; Female ; Genetic Linkage ; History, 20th Century ; Humans
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  • 15
    Publication Date: 2014-04-18
    Description: Centrosome amplification has long been recognized as a feature of human tumours; however, its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumours, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumour progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behaviour is similar to that induced by overexpression of the breast cancer oncogene ERBB2 (ref. 4) and indeed enhances invasiveness triggered by ERBB2. Our data indicate that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061398/" 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/PMC4061398/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Godinho, Susana A -- Picone, Remigio -- Burute, Mithila -- Dagher, Regina -- Su, Ying -- Leung, Cheuk T -- Polyak, Kornelia -- Brugge, Joan S -- Thery, Manuel -- Pellman, David -- 310472/European Research Council/International -- GM083299-1/GM/NIGMS NIH HHS/ -- R01 GM083299/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 5;510(7503):167-71. doi: 10.1038/nature13277. Epub 2014 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Pediatric Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK (S.A.G.); Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA (C.T.L.). ; 1] Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute and Pediatric Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Institut de Recherche en Technologie et Science pour le Vivant, UMR5168 CEA/UJF/INRA/CNRS, Grenoble, France [2] Hopital Saint Louis, Institut Universitaire d'Hematologie, U1160 INSERM/AP-HP/Universite Paris Diderot, Paris 75010, France [3] CYTOO SA, Grenoble 38054, France. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK (S.A.G.); Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455, USA (C.T.L.). ; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Institut de Recherche en Technologie et Science pour le Vivant, UMR5168 CEA/UJF/INRA/CNRS, Grenoble, France [2] Hopital Saint Louis, Institut Universitaire d'Hematologie, U1160 INSERM/AP-HP/Universite Paris Diderot, Paris 75010, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739973" target="_blank"〉PubMed〈/a〉
    Keywords: Aneuploidy ; Breast/cytology/pathology ; Breast Neoplasms/genetics/*pathology ; Cell Adhesion ; Cell Line ; Cell Transformation, Neoplastic/genetics/*pathology ; Centrosome/*pathology ; Disease Progression ; Enzyme Activation ; Epithelial Cells/cytology/pathology ; *Genes, erbB-2 ; Humans ; Microtubules/chemistry/metabolism/pathology ; Neoplasm Invasiveness/pathology ; Receptor, ErbB-2/genetics/metabolism ; rac1 GTP-Binding Protein/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 16
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 May 8;509(7499):133.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812679" target="_blank"〉PubMed〈/a〉
    Keywords: Goals ; History, 20th Century ; History, 21st Century ; *Interdisciplinary Studies ; Organisms, Genetically Modified ; Synthetic Biology/history/*manpower/*organization & administration
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  • 17
    Publication Date: 2014-07-22
    Description: Stable maintenance of gene regulatory programs is essential for normal function in multicellular organisms. Epigenetic mechanisms, and DNA methylation in particular, are hypothesized to facilitate such maintenance by creating cellular memory that can be written during embryonic development and then guide cell-type-specific gene expression. Here we develop new methods for quantitative inference of DNA methylation turnover rates, and show that human embryonic stem cells preserve their epigenetic state by balancing antagonistic processes that add and remove methylation marks rather than by copying epigenetic information from mother to daughter cells. In contrast, somatic cells transmit considerable epigenetic information to progenies. Paradoxically, the persistence of the somatic epigenome makes it more vulnerable to noise, since random epimutations can accumulate to massively perturb the epigenomic ground state. The rate of epigenetic perturbation depends on the genomic context, and, in particular, DNA methylation loss is coupled to late DNA replication dynamics. Epigenetic perturbation is not observed in the pluripotent state, because the rapid turnover-based equilibrium continuously reinforces the canonical state. This dynamic epigenetic equilibrium also explains how the epigenome can be reprogrammed quickly and to near perfection after induced pluripotency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shipony, Zohar -- Mukamel, Zohar -- Cohen, Netta Mendelson -- Landan, Gilad -- Chomsky, Elad -- Zeliger, Shlomit Reich -- Fried, Yael Chagit -- Ainbinder, Elena -- Friedman, Nir -- Tanay, Amos -- England -- Nature. 2014 Sep 4;513(7516):115-9. doi: 10.1038/nature13458. Epub 2014 Jul 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Computer Science and Applied Mathematics, and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel [2]. ; Department of Computer Science and Applied Mathematics, and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. ; 1] Department of Computer Science and Applied Mathematics, and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel [2] Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Biological Services, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043040" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cell Line ; Cell Line, Tumor ; Clone Cells/cytology/metabolism ; *DNA Methylation ; Embryonic Stem Cells/cytology/metabolism ; *Epigenesis, Genetic ; Fibroblasts/cytology/*metabolism ; Genome, Human/genetics ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism
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  • 18
    Publication Date: 2014-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kobilka, Brian -- Jamal Azouz, Haya -- England -- Nature. 2014 Oct 16;514(7522):S12-3. doi: 10.1038/514S12a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25317590" target="_blank"〉PubMed〈/a〉
    Keywords: Competitive Behavior ; Crystallization/history ; Crystallography, X-Ray/history ; History, 20th Century ; History, 21st Century ; Humans ; Nobel Prize ; Receptors, Adrenergic, beta-2/chemistry/history ; Receptors, G-Protein-Coupled/*chemistry/history/*metabolism ; Spectrometry, Fluorescence
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  • 19
    Publication Date: 2014-05-13
    Description: The global shortening of messenger RNAs through alternative polyadenylation (APA) that occurs during enhanced cellular proliferation represents an important, yet poorly understood mechanism of regulated gene expression. The 3' untranslated region (UTR) truncation of growth-promoting mRNA transcripts that relieves intrinsic microRNA- and AU-rich-element-mediated repression has been observed to correlate with cellular transformation; however, the importance to tumorigenicity of RNA 3'-end-processing factors that potentially govern APA is unknown. Here we identify CFIm25 as a broad repressor of proximal poly(A) site usage that, when depleted, increases cell proliferation. Applying a regression model on standard RNA-sequencing data for novel APA events, we identified at least 1,450 genes with shortened 3' UTRs after CFIm25 knockdown, representing 11% of significantly expressed mRNAs in human cells. Marked increases in the expression of several known oncogenes, including cyclin D1, are observed as a consequence of CFIm25 depletion. Importantly, we identified a subset of CFIm25-regulated APA genes with shortened 3' UTRs in glioblastoma tumours that have reduced CFIm25 expression. Downregulation of CFIm25 expression in glioblastoma cells enhances their tumorigenic properties and increases tumour size, whereas CFIm25 overexpression reduces these properties and inhibits tumour growth. These findings identify a pivotal role of CFIm25 in governing APA and reveal a previously unknown connection between CFIm25 and glioblastoma tumorigenicity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128630/" 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/PMC4128630/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masamha, Chioniso P -- Xia, Zheng -- Yang, Jingxuan -- Albrecht, Todd R -- Li, Min -- Shyu, Ann-Bin -- Li, Wei -- Wagner, Eric J -- CA166274/CA/NCI NIH HHS/ -- CA167752/CA/NCI NIH HHS/ -- GM046454/GM/NIGMS NIH HHS/ -- R01 GM046454/GM/NIGMS NIH HHS/ -- R01 HG007538/HG/NHGRI NIH HHS/ -- R01HG007538/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):412-6. doi: 10.1038/nature13261. Epub 2014 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA [2]. ; 1] Division of Biostatistics, Dan L Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, 77030 Texas, USA [2]. ; The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. ; Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. ; Division of Biostatistics, Dan L Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, 77030 Texas, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24814343" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Carcinogenesis/*genetics/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Glioblastoma/*physiopathology ; HeLa Cells ; Heterografts ; Humans ; Male ; Mice ; *Polyadenylation ; RNA, Messenger/*metabolism ; Regression Analysis ; mRNA Cleavage and Polyadenylation Factors/*metabolism
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  • 20
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jul 3;511(7507):6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24999505" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; History, 20th Century ; Periodicals as Topic/history ; Science/*history ; *World War I
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  • 21
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walker, John -- England -- Nature. 2014 Jan 2;505(7481):27. doi: 10.1038/505027a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24380948" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry/history ; Genomics/history/methods ; Great Britain ; History, 20th Century ; Humans ; Insulin/chemistry/history ; Nobel Prize ; Sequence Analysis/*history
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  • 22
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- Schiermeier, Quirin -- England -- Nature. 2014 Nov 6;515(7525):22-5. doi: 10.1038/515022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373658" target="_blank"〉PubMed〈/a〉
    Keywords: Berlin ; Communism/history ; Estonia ; European Union/economics ; History, 20th Century ; History, 21st Century ; Humans ; Hungary ; Poland ; Science/*economics/*trends
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  • 23
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-04-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Bernard -- England -- Nature. 2014 Apr 3;508(7494):31-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24707524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Asia ; *Biological Evolution ; *Fossils ; History, 20th Century ; Hominidae/anatomy & histology/*classification ; Kenya ; Paleontology/*history ; Phylogeny ; Tanzania
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  • 24
    Publication Date: 2014-09-12
    Description: To prime reverse transcription, retroviruses require annealing of a transfer RNA molecule to the U5 primer binding site (U5-PBS) region of the viral genome. The residues essential for primer annealing are initially locked in intramolecular interactions; hence, annealing requires the chaperone activity of the retroviral nucleocapsid (NC) protein to facilitate structural rearrangements. Here we show that, unlike classical chaperones, the Moloney murine leukaemia virus NC uses a unique mechanism for remodelling: it specifically targets multiple structured regions in both the U5-PBS and tRNA(Pro) primer that otherwise sequester residues necessary for annealing. This high-specificity and high-affinity binding by NC consequently liberates these sequestered residues--which are exactly complementary--for intermolecular interactions. Furthermore, NC utilizes a step-wise, entropy-driven mechanism to trigger both residue-specific destabilization and residue-specific release. Our structures of NC bound to U5-PBS and tRNA(Pro) reveal the structure-based mechanism for retroviral primer annealing and provide insights as to how ATP-independent chaperones can target specific RNAs amidst the cellular milieu of non-target RNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Sarah B -- Yildiz, F Zehra -- Lo, Jennifer A -- Wang, Bo -- D'Souza, Victoria M -- England -- Nature. 2014 Nov 27;515(7528):591-5. doi: 10.1038/nature13709. Epub 2014 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Biology, Georgetown University, Washington DC 20057, USA. [3]. ; 1] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2]. ; Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209668" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Genome, Viral/genetics ; Humans ; *Models, Molecular ; *Moloney murine leukemia virus/chemistry/genetics ; Nuclear Magnetic Resonance, Biomolecular ; *Nucleocapsid Proteins/chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary ; *RNA, Transfer/chemistry/metabolism ; RNA, Viral/*chemistry/*metabolism ; Reverse Transcription/genetics/*physiology
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  • 25
    Publication Date: 2014-08-01
    Description: In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell-type-specific regulation directed by DNA binding factors. This comparatively static landscape is in marked contrast with the events of fertilization, during which the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, although methylation remains detectable at several notable features. These dynamics have been extensively characterized in the mouse, with only limited observations available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies. Although most features share similar dynamics to those in mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island promoters that extend beyond known imprint control regions. Retrotransposon regulation is also highly diverse, and transitions from maternally to embryonically expressed elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178976/" 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/PMC4178976/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Zachary D -- Chan, Michelle M -- Humm, Kathryn C -- Karnik, Rahul -- Mekhoubad, Shila -- Regev, Aviv -- Eggan, Kevin -- Meissner, Alexander -- 1P50HG006193-01/HG/NHGRI NIH HHS/ -- 5DP1OD003958/OD/NIH HHS/ -- P01 GM099117/GM/NIGMS NIH HHS/ -- P01GM099117/GM/NIGMS NIH HHS/ -- P50 HG006193/HG/NHGRI NIH HHS/ -- U01 ES017155/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 31;511(7511):611-5. doi: 10.1038/nature13581. Epub 2014 Jul 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5]. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3]. ; 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Division of Reproductive Endocrinology &Infertility, Department of Obstetrics &Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA [3] Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts 02215, USA [4] Boston IVF, Waltham, Massachusetts 02451, USA [5] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [6]. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [3] Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079558" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*metabolism ; Cell Line ; CpG Islands/physiology ; DNA/metabolism ; *DNA Methylation ; Embryonic Stem Cells ; Female ; Gene Expression Regulation, Developmental ; Humans ; Male ; Mice ; Mice, Inbred C57BL
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  • 26
    Publication Date: 2014-11-11
    Description: Autophagy is an evolutionarily conserved catabolic process that recycles nutrients upon starvation and maintains cellular energy homeostasis. Its acute regulation by nutrient-sensing signalling pathways is well described, but its longer-term transcriptional regulation is not. The nuclear receptors peroxisome proliferator-activated receptor-alpha (PPARalpha) and farnesoid X receptor (FXR) are activated in the fasted and fed liver, respectively. Here we show that both PPARalpha and FXR regulate hepatic autophagy in mice. Pharmacological activation of PPARalpha reverses the normal suppression of autophagy in the fed state, inducing autophagic lipid degradation, or lipophagy. This response is lost in PPARalpha knockout (Ppara(-/-), also known as Nr1c1(-/-)) mice, which are partially defective in the induction of autophagy by fasting. Pharmacological activation of the bile acid receptor FXR strongly suppresses the induction of autophagy in the fasting state, and this response is absent in FXR knockout (Fxr(-/-), also known as Nr1h4(-/-)) mice, which show a partial defect in suppression of hepatic autophagy in the fed state. PPARalpha and FXR compete for binding to shared sites in autophagic gene promoters, with opposite transcriptional outputs. These results reveal complementary, interlocking mechanisms for regulation of autophagy by nutrient status.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267857/" 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/PMC4267857/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Jae Man -- Wagner, Martin -- Xiao, Rui -- Kim, Kang Ho -- Feng, Dan -- Lazar, Mitchell A -- Moore, David D -- DK43806/DK/NIDDK NIH HHS/ -- P30 DK019525/DK/NIDDK NIH HHS/ -- P30DX56338-05A2/PHS HHS/ -- P39CA125123-04/CA/NCI NIH HHS/ -- R01 DK049780/DK/NIDDK NIH HHS/ -- R01 DK49780/DK/NIDDK NIH HHS/ -- R37 DK043806/DK/NIDDK NIH HHS/ -- S10RR027783-01A1/RR/NCRR NIH HHS/ -- U54HD-07495-39/HD/NICHD NIH HHS/ -- England -- Nature. 2014 Dec 4;516(7529):112-5. doi: 10.1038/nature13961. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. ; Division of Endocrinology, Diabetes, and Metabolism and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19014, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/genetics/*physiology ; Cell Line ; Cells, Cultured ; Fasting/physiology ; Gene Expression Regulation ; Hepatocytes/metabolism ; Liver/cytology/*metabolism/ultrastructure ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins/genetics/metabolism ; PPAR alpha ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2014-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alvarez-Buylla, Arturo -- England -- Nature. 2014 Sep 4;513(7516):34. doi: 10.1038/513034a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, San Francisco, USA. He collaborated with Yoshiki Sasai between 2008 and 2014.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186892" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Embryonic Development ; History, 20th Century ; History, 21st Century ; Humans ; Neural Stem Cells/cytology ; Organoids/cytology ; Regenerative Medicine/*history ; Stem Cell Research/*history
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  • 28
    Publication Date: 2014-11-21
    Description: To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human-mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343047/" 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/PMC4343047/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Yong -- Ma, Zhihai -- Kim, Bong-Hyun -- Wu, Weisheng -- Cayting, Philip -- Boyle, Alan P -- Sundaram, Vasavi -- Xing, Xiaoyun -- Dogan, Nergiz -- Li, Jingjing -- Euskirchen, Ghia -- Lin, Shin -- Lin, Yiing -- Visel, Axel -- Kawli, Trupti -- Yang, Xinqiong -- Patacsil, Dorrelyn -- Keller, Cheryl A -- Giardine, Belinda -- Mouse ENCODE Consortium -- Kundaje, Anshul -- Wang, Ting -- Pennacchio, Len A -- Weng, Zhiping -- Hardison, Ross C -- Snyder, Michael P -- 1U54HG00699/HG/NHGRI NIH HHS/ -- 3RC2HG005602/HG/NHGRI NIH HHS/ -- 5U54HG006996/HG/NHGRI NIH HHS/ -- R01 DK065806/DK/NIDDK NIH HHS/ -- R01 DK096266/DK/NIDDK NIH HHS/ -- R01 ES024992/ES/NIEHS NIH HHS/ -- R01 EY021482/EY/NEI NIH HHS/ -- R01 GM083337/GM/NIGMS NIH HHS/ -- R01 HG003988/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG007175/HG/NHGRI NIH HHS/ -- R01 HG007348/HG/NHGRI NIH HHS/ -- R01 HG007354/HG/NHGRI NIH HHS/ -- R01DK065806/DK/NIDDK NIH HHS/ -- R01HG003988/HG/NHGRI NIH HHS/ -- R37 DK044746/DK/NIDDK NIH HHS/ -- RC2 HG005573/HG/NHGRI NIH HHS/ -- RC2 HG005602/HG/NHGRI NIH HHS/ -- RC2HG005573/HG/NHGRI NIH HHS/ -- U01 DE024427/DE/NIDCR NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG006996/HG/NHGRI NIH HHS/ -- U54 HG006997/HG/NHGRI NIH HHS/ -- U54 HG006998/HG/NHGRI NIH HHS/ -- U54 HG007004/HG/NHGRI NIH HHS/ -- U54HG006997/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Nov 20;515(7527):371-5. doi: 10.1038/nature13985.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, Stanford, California 94305, USA. ; Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; 1] Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA [2] BRCF Bioinformatics Core, University of Michigan, Ann Arbor, Michigan 48105, USA. ; Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, Missouri 63108, USA. ; Center for Comparative Genomics and Bioinformatics, Huck Institutes of the Life Sciences, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. ; 1] Department of Genetics, Stanford University, Stanford, California 94305, USA [2] Division of Cardiovascular Medicine, Stanford University, Stanford, California 94304, USA. ; 1] Department of Genetics, Stanford University, Stanford, California 94305, USA [2] Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; 1] Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California 94701, USA [2] Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA [3] School of Natural Sciences, University of California, Merced, California 95343, USA. ; 1] Lawrence Berkeley National Laboratory, Genomics Division, Berkeley, California 94701, USA [2] Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409826" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chromatin/genetics/metabolism ; Conserved Sequence/*genetics ; Enhancer Elements, Genetic/genetics ; Genome/*genetics ; *Genomics ; Humans ; Mice ; Polymorphism, Single Nucleotide/genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; Transcription Factors/*metabolism
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moyer, Melinda Wenner -- England -- Nature. 2014 Jun 26;510(7506):462-4. doi: 10.1038/510462a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24965635" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Beriberi/diet therapy/etiology/history/prevention & control ; *Dietary Supplements/utilization ; History, 20th Century ; Humans ; Nutritional Status/*drug effects ; Scurvy/diet therapy/etiology/history/prevention & control ; *Uncertainty ; Vitamins/history/*pharmacology
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  • 30
    Publication Date: 2014-09-26
    Description: For centuries, biogeographers have examined the factors that produce patterns of biodiversity across regions. The study of islands has proved particularly fruitful and has led to the theory that geographic area and isolation influence species colonization, extinction and speciation such that larger islands have more species and isolated islands have fewer species (that is, positive species-area and negative species-isolation relationships). However, experimental tests of this theory have been limited, owing to the difficulty in experimental manipulation of islands at the scales at which speciation and long-distance colonization are relevant. Here we have used the human-aided transport of exotic anole lizards among Caribbean islands as such a test at an appropriate scale. In accord with theory, as anole colonizations have increased, islands impoverished in native species have gained the most exotic species, the past influence of speciation on island biogeography has been obscured, and the species-area relationship has strengthened while the species-isolation relationship has weakened. Moreover, anole biogeography increasingly reflects anthropogenic rather than geographic processes. Unlike the island biogeography of the past that was determined by geographic area and isolation, in the Anthropocene--an epoch proposed for the present time interval--island biogeography is dominated by the economic isolation of human populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmus, Matthew R -- Mahler, D Luke -- Losos, Jonathan B -- England -- Nature. 2014 Sep 25;513(7519):543-6. doi: 10.1038/nature13739.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amsterdam Global Change Institute, Department of Animal Ecology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands. ; Center for Population Biology, University of California, Davis, California 95616, USA. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Commerce/history/statistics & numerical data ; Geography ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Human Activities/history/statistics & numerical data ; Introduced Species/history/*statistics & numerical data ; *Islands ; *Lizards/physiology ; Models, Biological ; Models, Economic ; Population Dynamics ; West Indies
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sohn, Emily -- England -- Nature. 2014 Nov 27;515(7528):S172-3. doi: 10.1038/515S172a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25427211" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; *Dogs ; Drug Evaluation, Preclinical/history ; Genetic Therapy ; Hemophilia A/*therapy ; Hemophilia B/*therapy ; History, 20th Century ; Research/trends
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  • 32
    Publication Date: 2014-01-31
    Description: The assessment of changes in tropical cyclone activity within the context of anthropogenically influenced climate change has been limited by the short temporal resolution of the instrumental tropical cyclone record (less than 50 years). Furthermore, controversy exists regarding the robustness of the observational record, especially before 1990. Here we show, on the basis of a new tropical cyclone activity index (CAI), that the present low levels of storm activity on the mid west and northeast coasts of Australia are unprecedented over the past 550 to 1,500 years. The CAI allows for a direct comparison between the modern instrumental record and long-term palaeotempest (prehistoric tropical cyclone) records derived from the (18)O/(16)O ratio of seasonally accreting carbonate layers of actively growing stalagmites. Our results reveal a repeated multicentennial cycle of tropical cyclone activity, the most recent of which commenced around AD 1700. The present cycle includes a sharp decrease in activity after 1960 in Western Australia. This is in contrast to the increasing frequency and destructiveness of Northern Hemisphere tropical cyclones since 1970 in the Atlantic Ocean and the western North Pacific Ocean. Other studies project a decrease in the frequency of tropical cyclones towards the end of the twenty-first century in the southwest Pacific, southern Indian and Australian regions. Our results, although based on a limited record, suggest that this may be occurring much earlier than expected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haig, Jordahna -- Nott, Jonathan -- Reichart, Gert-Jan -- England -- Nature. 2014 Jan 30;505(7485):667-71. doi: 10.1038/nature12882.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth and Environmental Sciences, James Cook University, Cairns, Queensland 4870, Australia. ; 1] Department of Geochemistry, Utrecht University, Utrecht 3508 TA, The Netherlands [2] Geology Department, Royal Netherlands Institute for Sea Research, Den Hoorn (Texel) 1797 SZ, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476890" target="_blank"〉PubMed〈/a〉
    Keywords: Atlantic Ocean ; Australia ; Carbon Isotopes ; Carbonates/analysis/chemistry ; Cyclonic Storms/*statistics & numerical data ; Global Warming/statistics & numerical data ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Human Activities ; Oxygen Isotopes ; Pacific Ocean ; Rain ; Seasons ; *Tropical Climate
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  • 33
    Publication Date: 2014-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rowe, Nicholas -- England -- Nature. 2014 May 8;509(7499):164. doi: 10.1038/509164e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Lapland, Rovaniemi, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805335" target="_blank"〉PubMed〈/a〉
    Keywords: *Congresses as Topic/history/trends ; History, 20th Century ; History, 21st Century ; *Posters as Topic ; *Research Personnel
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  • 34
    Publication Date: 2014-05-03
    Description: The response of the tropical climate in the Indian Ocean realm to abrupt climate change events in the North Atlantic Ocean is contentious. Repositioning of the intertropical convergence zone is thought to have been responsible for changes in tropical hydroclimate during North Atlantic cold spells, but the dearth of high-resolution records outside the monsoon realm in the Indian Ocean precludes a full understanding of this remote relationship and its underlying mechanisms. Here we show that slowdowns of the Atlantic meridional overturning circulation during Heinrich stadials and the Younger Dryas stadial affected the tropical Indian Ocean hydroclimate through changes to the Hadley circulation including a southward shift in the rising branch (the intertropical convergence zone) and an overall weakening over the southern Indian Ocean. Our results are based on new, high-resolution sea surface temperature and seawater oxygen isotope records of well-dated sedimentary archives from the tropical eastern Indian Ocean for the past 45,000 years, combined with climate model simulations of Atlantic circulation slowdown under Marine Isotope Stages 2 and 3 boundary conditions. Similar conditions in the east and west of the basin rule out a zonal dipole structure as the dominant forcing of the tropical Indian Ocean hydroclimate of millennial-scale events. Results from our simulations and proxy data suggest dry conditions in the northern Indian Ocean realm and wet and warm conditions in the southern realm during North Atlantic cold spells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohtadi, Mahyar -- Prange, Matthias -- Oppo, Delia W -- De Pol-Holz, Ricardo -- Merkel, Ute -- Zhang, Xiao -- Steinke, Stephan -- Luckge, Andreas -- England -- Nature. 2014 May 1;509(7498):76-80. doi: 10.1038/nature13196.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MARUM-Center for Marine Environmental Sciences, University of Bremen, 28359 Bremen, Germany. ; Geology and Geophysics, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts 02543, USA. ; Department of Oceanography, University of Concepcion, Concepcion, Chile. ; Federal Institute for Geosciences and Natural Resources, 30655 Hannover, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784218" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Air ; Atlantic Ocean ; Borneo ; Geologic Sediments/chemistry ; Greenland ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humidity ; Hydrology ; Ice Cover ; Indian Ocean ; Indonesia ; Lakes ; *Models, Theoretical ; Oxygen Isotopes ; Rain ; Salinity ; Seasons ; Seawater/analysis/chemistry ; Temperature ; Time Factors ; *Tropical Climate ; Water Movements
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  • 35
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2014 May 29;509(7502):546. doi: 10.1038/509546a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870524" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry/*history ; Animals ; Biological Evolution ; Breeding/*history ; *Chickens/classification/genetics ; Diet/veterinary ; Eggs ; Food Supply/history ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; History, Medieval ; Meat ; Oviposition/genetics ; *Research
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  • 36
    Publication Date: 2014-03-29
    Description: Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andersson, Robin -- Gebhard, Claudia -- Miguel-Escalada, Irene -- Hoof, Ilka -- Bornholdt, Jette -- Boyd, Mette -- Chen, Yun -- Zhao, Xiaobei -- Schmidl, Christian -- Suzuki, Takahiro -- Ntini, Evgenia -- Arner, Erik -- Valen, Eivind -- Li, Kang -- Schwarzfischer, Lucia -- Glatz, Dagmar -- Raithel, Johanna -- Lilje, Berit -- Rapin, Nicolas -- Bagger, Frederik Otzen -- Jorgensen, Mette -- Andersen, Peter Refsing -- Bertin, Nicolas -- Rackham, Owen -- Burroughs, A Maxwell -- Baillie, J Kenneth -- Ishizu, Yuri -- Shimizu, Yuri -- Furuhata, Erina -- Maeda, Shiori -- Negishi, Yutaka -- Mungall, Christopher J -- Meehan, Terrence F -- Lassmann, Timo -- Itoh, Masayoshi -- Kawaji, Hideya -- Kondo, Naoto -- Kawai, Jun -- Lennartsson, Andreas -- Daub, Carsten O -- Heutink, Peter -- Hume, David A -- Jensen, Torben Heick -- Suzuki, Harukazu -- Hayashizaki, Yoshihide -- Muller, Ferenc -- FANTOM Consortium -- Forrest, Alistair R R -- Carninci, Piero -- Rehli, Michael -- Sandelin, Albin -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):455-61. doi: 10.1038/nature12787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2]. ; 1] Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany [2] Regensburg Centre for Interventional Immunology (RCI), D-93042 Regensburg, Germany [3]. ; School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. ; The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, C.F. Mollers Alle 3, Building 1130, DK-8000 Aarhus, Denmark. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark [2] The Finsen Laboratory, Rigshospitalet and Danish Stem Cell Centre (DanStem), University of Copenhagen, Ole Maaloes Vej 5, DK-2200, Denmark. ; Roslin Institute, Edinburgh University, Easter Bush, Midlothian, Edinburgh EH25 9RG, UK. ; Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road MS 64-121, Berkeley, California 94720, USA. ; EMBL Outstation - Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [3] RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan. ; Department of Biosciences and Nutrition, Karolinska Institutet, Halsovagen 7, SE-4183 Huddinge, Stockholm, Sweden. ; 1] RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [2] RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan [3] Department of Biosciences and Nutrition, Karolinska Institutet, Halsovagen 7, SE-4183 Huddinge, Stockholm, Sweden. ; Department of Clinical Genetics, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands. ; 1] Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany [2] Regensburg Centre for Interventional Immunology (RCI), D-93042 Regensburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670763" target="_blank"〉PubMed〈/a〉
    Keywords: *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Genetic Predisposition to Disease/genetics ; HeLa Cells ; Humans ; *Molecular Sequence Annotation ; *Organ Specificity ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; RNA, Messenger/biosynthesis/genetics ; Transcription Initiation Site ; Transcription Initiation, Genetic
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  • 37
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heymann, David L -- England -- Nature. 2014 Oct 16;514(7522):299-300. doi: 10.1038/514299a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318509" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Western/epidemiology ; Cities/epidemiology ; *Clinical Trials as Topic/ethics ; Congo/epidemiology ; *Contact Tracing ; Cross Infection/epidemiology ; Disease Outbreaks/prevention & control/statistics & numerical data ; Fever/diagnosis ; Funeral Rites ; *Hemorrhagic Fever, Ebola/diagnosis/epidemiology/prevention & ; control/therapy/transmission ; History, 20th Century ; History, 21st Century ; Humans ; Plasmapheresis/utilization ; Protective Clothing ; *Quarantine ; Rural Population/statistics & numerical data ; Survivors ; Time Factors ; Urban Population/statistics & numerical data ; World Health Organization
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  • 38
    Publication Date: 2014-02-21
    Description: Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murthy, Aditya -- Li, Yun -- Peng, Ivan -- Reichelt, Mike -- Katakam, Anand Kumar -- Noubade, Rajkumar -- Roose-Girma, Merone -- DeVoss, Jason -- Diehl, Lauri -- Graham, Robert R -- van Lookeren Campagne, Menno -- England -- Nature. 2014 Feb 27;506(7489):456-62. doi: 10.1038/nature13044. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. ; ITGR Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553140" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Autophagy/genetics ; Carrier Proteins/chemistry/*genetics/*metabolism ; Caspase 3/deficiency/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Crohn Disease/*genetics/pathology ; Cytokines/immunology ; Enzyme Activation ; Female ; Food Deprivation ; Humans ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mutagenesis, Site-Directed ; Polymorphism, Single Nucleotide/*genetics ; *Proteolysis ; Stress, Physiological ; Yersinia enterocolitica/immunology
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  • 39
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rutishauser, Urs -- England -- Nature. 2014 Jun 26;510(7506):474. doi: 10.1038/510474a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sloan Kettering Institute at the Memorial Sloan Kettering Cancer Center in New York. He was a student and colleague in Gerald Edelman's laboratory at Rockefeller University in New York from 1967 to 1983.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24965643" target="_blank"〉PubMed〈/a〉
    Keywords: Allergy and Immunology/*history ; Antibodies/chemistry/immunology ; California ; History, 20th Century ; Mentors ; Models, Immunological ; Models, Neurological ; Neurosciences/*history ; New York City ; Nobel Prize
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  • 40
    Publication Date: 2014-07-22
    Description: Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162811/" 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/PMC4162811/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Bo -- Qiu, Bo -- Lee, David S M -- Walton, Zandra E -- Ochocki, Joshua D -- Mathew, Lijoy K -- Mancuso, Anthony -- Gade, Terence P F -- Keith, Brian -- Nissim, Itzhak -- Simon, M Celeste -- CA104838/CA/NCI NIH HHS/ -- DK053761/DK/NIDDK NIH HHS/ -- F30 CA177106/CA/NCI NIH HHS/ -- F32 CA192758/CA/NCI NIH HHS/ -- P01 CA104838/CA/NCI NIH HHS/ -- P30 CA016520/CA/NCI NIH HHS/ -- R01 DK053761/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Sep 11;513(7517):251-5. doi: 10.1038/nature13557. Epub 2014 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [3] Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; 1] Department of Pediatrics, Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Division of Child Development and Metabolic Disease, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. ; 1] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104, USA [3] Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043030" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Carcinoma, Renal Cell/*enzymology/genetics/physiopathology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Disease Progression ; Epithelial Cells/metabolism ; Fructose-Bisphosphatase/chemistry/genetics/*metabolism ; Glycolysis ; Humans ; Kidney Neoplasms/*enzymology/genetics/physiopathology ; Models, Molecular ; NADP/metabolism ; Protein Structure, Tertiary ; Swine
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  • 41
    Publication Date: 2014-08-21
    Description: Saturation mutagenesis--coupled to an appropriate biological assay--represents a fundamental means of achieving a high-resolution understanding of regulatory and protein-coding nucleic acid sequences of interest. However, mutagenized sequences introduced in trans on episomes or via random or "safe-harbour" integration fail to capture the native context of the endogenous chromosomal locus. This shortcoming markedly limits the interpretability of the resulting measurements of mutational impact. Here, we couple CRISPR/Cas9 RNA-guided cleavage with multiplex homology-directed repair using a complex library of donor templates to demonstrate saturation editing of genomic regions. In exon 18 of BRCA1, we replace a six-base-pair (bp) genomic region with all possible hexamers, or the full exon with all possible single nucleotide variants (SNVs), and measure strong effects on transcript abundance attributable to nonsense-mediated decay and exonic splicing elements. We similarly perform saturation genome editing of a well-conserved coding region of an essential gene, DBR1, and measure relative effects on growth that correlate with functional impact. Measurement of the functional consequences of large numbers of mutations with saturation genome editing will potentially facilitate high-resolution functional dissection of both cis-regulatory elements and trans-acting factors, as well as the interpretation of variants of uncertain significance observed in clinical sequencing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156553/" 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/PMC4156553/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Findlay, Gregory M -- Boyle, Evan A -- Hause, Ronald J -- Klein, Jason C -- Shendure, Jay -- DP1 HG007811/HG/NHGRI NIH HHS/ -- DP1HG007811/DP/NCCDPHP CDC HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Sep 4;513(7516):120-3. doi: 10.1038/nature13695.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA [2]. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25141179" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Associated Proteins/metabolism ; CRISPR-Cas Systems/genetics ; Cell Line ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Conserved Sequence/genetics ; Exons/genetics ; Genes, BRCA1 ; Genes, Essential/genetics ; Genomics/*methods ; Humans ; Molecular Sequence Annotation/*methods ; Mutagenesis/*genetics ; Nonsense Mediated mRNA Decay ; Open Reading Frames/genetics ; Point Mutation/genetics ; RNA Nucleotidyltransferases/genetics ; RNA Splicing/genetics ; Recombinational DNA Repair/*genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Templates, Genetic
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  • 42
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    Publication Date: 2014-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 May 22;509(7501):410. doi: 10.1038/509410a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24848041" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Crowdsourcing ; *Data Mining ; Forecasting/*methods ; History, 20th Century ; History, 21st Century ; *Language ; Patents as Topic/*statistics & numerical data ; Research/*trends ; Software ; Solar Energy/economics/history
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  • 43
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    Publication Date: 2014-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ellis, R John -- England -- Nature. 2014 May 15;509(7500):288. doi: 10.1038/509288b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Warwick, Coventry, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828181" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autobiography as Topic ; History, 20th Century ; Polysaccharides ; Prions/*history/radiation effects ; Scrapie/*etiology/*history
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Monya -- England -- Nature. 2014 Jan 16;505(7483):272. doi: 10.1038/505272a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24429608" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Specimen Banks/*economics/history ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Cooperative Behavior ; History, 20th Century ; History, 21st Century ; *Research ; Research Personnel ; United States
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  • 45
    Publication Date: 2014-01-28
    Description: H2A.Z is an essential histone variant implicated in the regulation of key nuclear events. However, the metazoan chaperones responsible for H2A.Z deposition and its removal from chromatin remain unknown. Here we report the identification and characterization of the human protein ANP32E as a specific H2A.Z chaperone. We show that ANP32E is a member of the presumed H2A.Z histone-exchange complex p400/TIP60. ANP32E interacts with a short region of the docking domain of H2A.Z through a new motif termed H2A.Z interacting domain (ZID). The 1.48 A resolution crystal structure of the complex formed between the ANP32E-ZID and the H2A.Z/H2B dimer and biochemical data support an underlying molecular mechanism for H2A.Z/H2B eviction from the nucleosome and its stabilization by ANP32E through a specific extension of the H2A.Z carboxy-terminal alpha-helix. Finally, analysis of H2A.Z localization in ANP32E(-/-) cells by chromatin immunoprecipitation followed by sequencing shows genome-wide enrichment, redistribution and accumulation of H2A.Z at specific chromatin control regions, in particular at enhancers and insulators.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Obri, Arnaud -- Ouararhni, Khalid -- Papin, Christophe -- Diebold, Marie-Laure -- Padmanabhan, Kiran -- Marek, Martin -- Stoll, Isabelle -- Roy, Ludovic -- Reilly, Patrick T -- Mak, Tak W -- Dimitrov, Stefan -- Romier, Christophe -- Hamiche, Ali -- England -- Nature. 2014 Jan 30;505(7485):648-53. doi: 10.1038/nature12922. Epub 2014 Jan 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Departement de Genomique Fonctionnelle et Cancer, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France [2]. ; Departement de Biologie Structurale Integrative, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. ; Equipe labelisee Ligue contre le Cancer, INSERM/Universite Joseph Fourier , Institut Albert Bonniot, U823, Site Sante-BP 170, 38042 Grenoble Cedex 9, France. ; Departement de Genomique Fonctionnelle et Cancer, Institut de Genetique et Biologie Moleculaire et Cellulaire (IGBMC), Universite de Strasbourg, CNRS, INSERM, 1 rue Laurent Fries, B.P. 10142, 67404 Illkirch Cedex, France. ; Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore. ; 1] Laboratory of Inflammation Biology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore [2] The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463511" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Cell Nucleus/chemistry/metabolism ; Chromatin/*chemistry/genetics/*metabolism ; Chromatin Immunoprecipitation ; Crystallography, X-Ray ; DNA/genetics/metabolism ; Genome, Human/genetics ; Histones/chemistry/isolation & purification/*metabolism ; Humans ; Models, Molecular ; Molecular Chaperones/chemistry/*metabolism ; Molecular Sequence Data ; Nuclear Proteins/chemistry/*metabolism ; Nucleosomes/chemistry/metabolism ; Phosphoproteins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Substrate Specificity
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  • 46
    Publication Date: 2014-07-11
    Description: Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Hong -- Morey, Robert -- O'Neil, Ryan C -- He, Yupeng -- Daughtry, Brittany -- Schultz, Matthew D -- Hariharan, Manoj -- Nery, Joseph R -- Castanon, Rosa -- Sabatini, Karen -- Thiagarajan, Rathi D -- Tachibana, Masahito -- Kang, Eunju -- Tippner-Hedges, Rebecca -- Ahmed, Riffat -- Gutierrez, Nuria Marti -- Van Dyken, Crystal -- Polat, Alim -- Sugawara, Atsushi -- Sparman, Michelle -- Gokhale, Sumita -- Amato, Paula -- Wolf, Don P -- Ecker, Joseph R -- Laurent, Louise C -- Mitalipov, Shoukhrat -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):177-83. doi: 10.1038/nature13551. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3]. ; 1] Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA [2]. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Bioinformatics Program, University of California at San Diego, La Jolla, California 92093, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA. ; 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [2] Department of Obstetrics and Gynecology, South Miyagi Medical Center, Shibata-gun, Miyagi 989-1253, Japan (M.T.); Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden (A.P.). ; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; University Pathologists LLC, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02118, USA. ; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3] Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Cellular Reprogramming ; Chromosome Aberrations ; Chromosomes, Human, X/genetics/metabolism ; DNA Copy Number Variations ; DNA Methylation ; Genome-Wide Association Study ; Genomic Imprinting ; Humans ; Nuclear Transfer Techniques/standards ; Pluripotent Stem Cells/cytology/*metabolism ; Transcriptome
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  • 47
    Publication Date: 2014-12-18
    Description: During endocytosis, energy is invested to narrow the necks of cargo-containing plasma membrane invaginations to radii at which the opposing segments spontaneously coalesce, thereby leading to the detachment by scission of endocytic uptake carriers. In the clathrin pathway, dynamin uses mechanical energy from GTP hydrolysis to this effect, assisted by the BIN/amphiphysin/Rvs (BAR) domain-containing protein endophilin. Clathrin-independent endocytic events are often less reliant on dynamin, and whether in these cases BAR domain proteins such as endophilin contribute to scission has remained unexplored. Here we show, in human and other mammalian cell lines, that endophilin-A2 (endoA2) specifically and functionally associates with very early uptake structures that are induced by the bacterial Shiga and cholera toxins, which are both clathrin-independent endocytic cargoes. In controlled in vitro systems, endoA2 reshapes membranes before scission. Furthermore, we demonstrate that endoA2, dynamin and actin contribute in parallel to the scission of Shiga-toxin-induced tubules. Our results establish a novel function of endoA2 in clathrin-independent endocytosis. They document that distinct scission factors operate in an additive manner, and predict that specificity within a given uptake process arises from defined combinations of universal modules. Our findings highlight a previously unnoticed link between membrane scaffolding by endoA2 and pulling-force-driven dynamic scission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342003/" 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/PMC4342003/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Renard, Henri-Francois -- Simunovic, Mijo -- Lemiere, Joel -- Boucrot, Emmanuel -- Garcia-Castillo, Maria Daniela -- Arumugam, Senthil -- Chambon, Valerie -- Lamaze, Christophe -- Wunder, Christian -- Kenworthy, Anne K -- Schmidt, Anne A -- McMahon, Harvey T -- Sykes, Cecile -- Bassereau, Patricia -- Johannes, Ludger -- R01 GM106720/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 22;517(7535):493-6. doi: 10.1038/nature14064. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institut Curie - Centre de Recherche, Endocytic Trafficking and Therapeutic Delivery group, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] CNRS UMR3666, 75005 Paris, France [3] U1143 INSERM, 75005 Paris, France. ; 1] Institut Curie - Centre de Recherche, Membrane and Cell Functions group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] The University of Chicago, Department of Chemistry, 5735 S Ellis Ave, Chicago, Ilinois 60637, USA. ; 1] Institut Curie - Centre de Recherche, Biomimetism of Cell Movement group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France [2] Universite Paris Diderot, Sorbonne Paris Cite, 75205 Paris, France. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; 1] CNRS UMR3666, 75005 Paris, France [2] U1143 INSERM, 75005 Paris, France [3] Institut Curie - Centre de Recherche, Membrane Dynamics and Mechanics of Intracellular Signaling group, 26 rue d'Ulm, 75248 Paris Cedex 05, France. ; Vanderbilt School of Medicine, Department of Molecular Physiology and Biophysics, 718 Light Hall, Nashville, Tennessee 37232, USA. ; CNRS, UMR7592, Institut Jacques Monod, Universite Paris Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris Cedex 13, France. ; Medical Research Council, Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; Institut Curie - Centre de Recherche, Biomimetism of Cell Movement group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. ; Institut Curie - Centre de Recherche, Membrane and Cell Functions group, CNRS UMR 168, Physico-Chimie Curie, Universite Pierre et Marie Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517096" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Acyltransferases/*metabolism ; Animals ; Cell Line ; Cell Membrane/*metabolism ; Cholera Toxin/metabolism ; Clathrin ; Dynamins/metabolism ; *Endocytosis ; Humans ; Rats ; Shiga Toxin/metabolism
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  • 48
    Publication Date: 2014-06-05
    Description: Srs2 helicase is known to dismantle nucleofilaments of Rad51 recombinase to prevent spurious recombination events and unwind trinucleotide sequences that are prone to hairpin formation. Here we document a new, unexpected genome maintenance role of Srs2 in the suppression of mutations arising from mis-insertion of ribonucleoside monophosphates during DNA replication. In cells lacking RNase H2, Srs2 unwinds DNA from the 5' side of a nick generated by DNA topoisomerase I at a ribonucleoside monophosphate residue. In addition, Srs2 interacts with and enhances the activity of the nuclease Exo1, to generate a DNA gap in preparation for repair. Srs2-Exo1 thus functions in a new pathway of nick processing-gap filling that mediates tolerance of ribonucleoside monophosphates in the genome. Our results have implications for understanding the basis of Aicardi-Goutieres syndrome, which stems from inactivation of the human RNase H2 complex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140095/" 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/PMC4140095/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Potenski, Catherine J -- Niu, Hengyao -- Sung, Patrick -- Klein, Hannah L -- K99 ES021441/ES/NIEHS NIH HHS/ -- K99ES021441/ES/NIEHS NIH HHS/ -- R01 ES007061/ES/NIEHS NIH HHS/ -- R01 GM053738/GM/NIGMS NIH HHS/ -- R01ES007061/ES/NIEHS NIH HHS/ -- R01GM053738/GM/NIGMS NIH HHS/ -- UL1 TR000142/TR/NCATS NIH HHS/ -- England -- Nature. 2014 Jul 10;511(7508):251-4. doi: 10.1038/nature13292. Epub 2014 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2]. ; 1] Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA [2]. ; Molecular Biophysics and Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA. ; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896181" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; DNA Damage/genetics ; DNA Helicases/genetics/*metabolism ; Escherichia coli/genetics ; Exodeoxyribonucleases/genetics/*metabolism ; Genomic Instability/*genetics ; Mutation/*genetics ; Ribonuclease H/*metabolism ; Ribonucleotides/*metabolism ; Saccharomyces cerevisiae/*enzymology/*genetics ; Saccharomyces cerevisiae Proteins/genetics/*metabolism
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  • 49
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brooke, Michael -- England -- Nature. 2014 Sep 25;513(7519):484-5. doi: 10.1038/513484a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University Museum of Zoology in Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254461" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/anatomy & histology/*physiology ; *Courtship ; Female ; Habits ; History, 20th Century ; Humans ; Male ; Mating Preference, Animal
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  • 50
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiner, Kevin S -- England -- Nature. 2014 May 1;509(7498):33. doi: 10.1038/509033e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University; and the Institute for Applied Neuroscience, California, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784209" target="_blank"〉PubMed〈/a〉
    Keywords: Cerebral Cortex/*anatomy & histology ; Famous Persons ; History, 19th Century ; History, 20th Century ; Surface Tension
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  • 51
    Publication Date: 2014-10-09
    Description: The formation of R-loops is a natural consequence of the transcription process, caused by invasion of the DNA duplex by nascent transcripts. These structures have been considered rare transcriptional by-products with potentially harmful effects on genome integrity owing to the fragility of the displaced DNA coding strand. However, R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes. Furthermore, we have previously shown that R-loops are particularly enriched over G-rich terminator elements. These facilitate RNA polymerase II (Pol II) pausing before efficient termination. Here we reveal an unanticipated link between R-loops and RNA-interference-dependent H3K9me2 formation over pause-site termination regions in mammalian protein-coding genes. We show that R-loops induce antisense transcription over these pause elements, which in turn leads to the generation of double-stranded RNA and the recruitment of DICER, AGO1, AGO2 and the G9a histone lysine methyltransferase. Consequently, an H3K9me2 repressive mark is formed and heterochromatin protein 1gamma (HP1gamma) is recruited, which reinforces Pol II pausing before efficient transcriptional termination. We predict that R-loops promote a chromatin architecture that defines the termination region for a substantial subset of mammalian genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272244/" 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/PMC4272244/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Skourti-Stathaki, Konstantina -- Kamieniarz-Gdula, Kinga -- Proudfoot, Nicholas J -- 091805/Wellcome Trust/United Kingdom -- 091805/Z/10/Z/Wellcome Trust/United Kingdom -- 091911/Wellcome Trust/United Kingdom -- 339270/European Research Council/International -- England -- Nature. 2014 Dec 18;516(7531):436-9. doi: 10.1038/nature13787. Epub 2014 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford OX1 3RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296254" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/genetics ; Animals ; Argonaute Proteins/metabolism ; Cell Line ; Chromatin/*metabolism ; *Gene Expression Regulation ; HeLa Cells ; Histocompatibility Antigens/metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/metabolism ; Humans ; Mice ; RNA Interference ; RNA Polymerase II/metabolism ; Terminator Regions, Genetic/*genetics
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  • 52
    Publication Date: 2014-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wong, Min-Liang -- England -- Nature. 2014 Oct 9;514(7521):168. doi: 10.1038/514168e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Chung-Hsing University, Taiwan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25297426" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Light Signal Transduction ; *Nobel Prize ; *Photosynthesis ; *Physics
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  • 53
    Publication Date: 2014-05-30
    Description: Proteomes are characterized by large protein-abundance differences, cell-type- and time-dependent expression patterns and post-translational modifications, all of which carry biological information that is not accessible by genomics or transcriptomics. Here we present a mass-spectrometry-based draft of the human proteome and a public, high-performance, in-memory database for real-time analysis of terabytes of big data, called ProteomicsDB. The information assembled from human tissues, cell lines and body fluids enabled estimation of the size of the protein-coding genome, and identified organ-specific proteins and a large number of translated lincRNAs (long intergenic non-coding RNAs). Analysis of messenger RNA and protein-expression profiles of human tissues revealed conserved control of protein abundance, and integration of drug-sensitivity data enabled the identification of proteins predicting resistance or sensitivity. The proteome profiles also hold considerable promise for analysing the composition and stoichiometry of protein complexes. ProteomicsDB thus enables navigation of proteomes, provides biological insight and fosters the development of proteomic technology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Mathias -- Schlegl, Judith -- Hahne, Hannes -- Moghaddas Gholami, Amin -- Lieberenz, Marcus -- Savitski, Mikhail M -- Ziegler, Emanuel -- Butzmann, Lars -- Gessulat, Siegfried -- Marx, Harald -- Mathieson, Toby -- Lemeer, Simone -- Schnatbaum, Karsten -- Reimer, Ulf -- Wenschuh, Holger -- Mollenhauer, Martin -- Slotta-Huspenina, Julia -- Boese, Joos-Hendrik -- Bantscheff, Marcus -- Gerstmair, Anja -- Faerber, Franz -- Kuster, Bernhard -- England -- Nature. 2014 May 29;509(7502):582-7. doi: 10.1038/nature13319.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Chair of Proteomics and Bioanalytics, Technische Universitat Munchen, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany [2] SAP AG, Dietmar-Hopp-Allee 16, 69190 Walldorf, Germany [3]. ; 1] SAP AG, Dietmar-Hopp-Allee 16, 69190 Walldorf, Germany [2]. ; 1] Chair of Proteomics and Bioanalytics, Technische Universitat Munchen, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany [2]. ; SAP AG, Dietmar-Hopp-Allee 16, 69190 Walldorf, Germany. ; Cellzome GmbH, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; Chair of Proteomics and Bioanalytics, Technische Universitat Munchen, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany. ; JPT Peptide Technologies GmbH, Volmerstrasse 5, 12489 Berlin, Germany. ; Institute of Pathology, Technische Universitat Munchen, Trogerstrasse 18, 81675 Munchen, Germany. ; 1] Chair of Proteomics and Bioanalytics, Technische Universitat Munchen, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany [2] Center for Integrated Protein Science Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870543" target="_blank"〉PubMed〈/a〉
    Keywords: Body Fluids/chemistry/metabolism ; Cell Line ; *Databases, Protein ; Gene Expression Profiling ; Genome, Human/genetics ; Humans ; *Mass Spectrometry ; Molecular Sequence Annotation ; Organ Specificity ; Proteome/*analysis/*chemistry/genetics/metabolism ; *Proteomics ; RNA, Messenger/analysis/genetics
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  • 54
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    Nature Publishing Group (NPG)
    Publication Date: 2014-07-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fara, Patricia -- England -- Nature. 2014 Jul 3;511(7507):25-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24999506" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Science/history/*manpower ; Sexism/history ; Women's Rights/*history ; *World War I
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  • 55
    Publication Date: 2014-05-09
    Description: ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP(+) to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP(+) and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104482/" 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/PMC4104482/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fan, Jing -- Ye, Jiangbin -- Kamphorst, Jurre J -- Shlomi, Tomer -- Thompson, Craig B -- Rabinowitz, Joshua D -- P01 CA104838/CA/NCI NIH HHS/ -- P30 CA072720/CA/NCI NIH HHS/ -- P50 GM071508/GM/NIGMS NIH HHS/ -- R01 AI097382/AI/NIAID NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- R01 CA163591/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 12;510(7504):298-302. doi: 10.1038/nature13236. Epub 2014 May 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Chemistry and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA [2]. ; 1] Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2]. ; Department of Chemistry and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA. ; 1] Department of Chemistry and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA [2] Department of Computer Science, Technion - Israel Institute of Technology, Haifa 32000, Israel. ; Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24805240" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon/metabolism ; Cell Line ; Cell Line, Tumor ; Cytosol/enzymology/metabolism ; Folic Acid/*metabolism ; Glutathione/metabolism ; Glycine/metabolism ; HEK293 Cells ; Humans ; Isoenzymes/deficiency/genetics/metabolism ; Leucovorin/analogs & derivatives/metabolism ; Methylenetetrahydrofolate Dehydrogenase (NADP)/deficiency/genetics/metabolism ; Mice ; Mitochondria/enzymology/metabolism ; NADP/*biosynthesis/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Pentose Phosphate Pathway ; Serine/metabolism ; Tetrahydrofolates/metabolism
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  • 56
    Publication Date: 2014-01-31
    Description: Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other 'housekeeping' proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086860/" 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/PMC4086860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Subtelny, Alexander O -- Eichhorn, Stephen W -- Chen, Grace R -- Sive, Hazel -- Bartel, David P -- GM067031/GM/NIGMS NIH HHS/ -- R01 GM067031/GM/NIGMS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 3;508(7494):66-71. doi: 10.1038/nature13007. Epub 2014 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4] Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA [5]. ; 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [4]. ; 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476825" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arabidopsis/genetics ; Base Sequence ; Cell Line ; Drosophila melanogaster/embryology/genetics ; Gastrulation/genetics ; Gene Expression Regulation, Developmental/*genetics ; Humans ; Liver/metabolism ; Mice ; MicroRNAs/genetics/metabolism ; Models, Genetic ; Plant Leaves/genetics ; Poly A/*analysis/genetics ; Protein Biosynthesis/*genetics ; RNA Stability/genetics ; RNA, Messenger/*genetics/metabolism ; Ribosomes/metabolism ; Sequence Analysis, RNA ; Species Specificity ; Transcription, Genetic ; Xenopus/embryology/genetics ; Yeasts/genetics ; Zebrafish/embryology/genetics ; Zygote/metabolism
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2014-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ratcliff, Peter -- Hoffman, Jascha -- England -- Nature. 2014 Sep 25;513(7519):486. doi: 10.1038/513486a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25254463" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustics ; Climate ; History, 17th Century ; History, 18th Century ; History, 20th Century ; Music/*history ; *Picea/anatomy & histology/growth & development ; Soil ; Weather ; *Wood
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  • 58
    Publication Date: 2014-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rousseau, Ronald -- England -- Nature. 2014 Jun 12;510(7504):218. doi: 10.1038/510218e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉KU Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919911" target="_blank"〉PubMed〈/a〉
    Keywords: Bibliometrics/*history ; History, 20th Century ; Internet ; Library Science/*history
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  • 59
    Publication Date: 2014-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kutschera, U -- England -- Nature. 2014 Jun 12;510(7504):218. doi: 10.1038/510218a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biology, University of Kassel, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919913" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Hermaphroditic Organisms ; History, 20th Century ; Humans ; Phylogeny ; Selection, Genetic ; Women's Rights/*history
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  • 60
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jan 30;505(7485):586.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482832" target="_blank"〉PubMed〈/a〉
    Keywords: Anniversaries and Special Events ; Crystallography, X-Ray/*history/trends ; History, 20th Century ; History, 21st Century ; Quantum Theory/history
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  • 61
    Publication Date: 2014-05-16
    Description: Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that alpha-ketoglutarate (alpha-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit beta is identified as a novel binding protein of alpha-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that alpha-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by alpha-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by alpha-KG requires ATP synthase subunit beta and is dependent on target of rapamycin (TOR) downstream. Endogenous alpha-KG levels are increased on starvation and alpha-KG does not extend the lifespan of dietary-restricted animals, indicating that alpha-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263271/" 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/PMC4263271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chin, Randall M -- Fu, Xudong -- Pai, Melody Y -- Vergnes, Laurent -- Hwang, Heejun -- Deng, Gang -- Diep, Simon -- Lomenick, Brett -- Meli, Vijaykumar S -- Monsalve, Gabriela C -- Hu, Eileen -- Whelan, Stephen A -- Wang, Jennifer X -- Jung, Gwanghyun -- Solis, Gregory M -- Fazlollahi, Farbod -- Kaweeteerawat, Chitrada -- Quach, Austin -- Nili, Mahta -- Krall, Abby S -- Godwin, Hilary A -- Chang, Helena R -- Faull, Kym F -- Guo, Feng -- Jiang, Meisheng -- Trauger, Sunia A -- Saghatelian, Alan -- Braas, Daniel -- Christofk, Heather R -- Clarke, Catherine F -- Teitell, Michael A -- Petrascheck, Michael -- Reue, Karen -- Jung, Michael E -- Frand, Alison R -- Huang, Jing -- DP2 OD008398/OD/NIH HHS/ -- P01 HL028481/HL/NHLBI NIH HHS/ -- P40 OD010440/OD/NIH HHS/ -- T32 CA009120/CA/NCI NIH HHS/ -- T32 GM007104/GM/NIGMS NIH HHS/ -- T32 GM007185/GM/NIGMS NIH HHS/ -- T32 GM008496/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Jun 19;510(7505):397-401. doi: 10.1038/nature13264. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2]. ; 1] Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA [2]. ; 1] Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA [2]. ; Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Surgery, University of California Los Angeles, Los Angeles, California 90095, USA. ; Small Molecule Mass Spectrometry Facility, FAS Division of Science, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA. ; Pasarow Mass Spectrometry Laboratory, Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Environmental Health Sciences, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. ; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; 1] Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA [2] UCLA Metabolomics Center, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Human Genetics, University of California Los Angeles, Los Angeles, California 90095, USA. ; 1] Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA [2] Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828042" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*drug effects ; Cell Line ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Jurkat Cells ; Ketoglutaric Acids/*pharmacology ; Longevity/drug effects/genetics/*physiology ; Mice ; Mitochondrial Proton-Translocating ATPases/genetics/*metabolism ; Protein Binding ; TOR Serine-Threonine Kinases/*metabolism
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  • 62
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jan 30;505(7485):601. doi: 10.1038/505601a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24476870" target="_blank"〉PubMed〈/a〉
    Keywords: *Crystallography, X-Ray/history/trends ; History, 20th Century
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  • 63
    Publication Date: 2014-06-12
    Description: Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR) defend against pathogen infection by activating caspase 1. Pyrin, a candidate PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating complex. Mutations in the Pyrin-encoding gene, MEFV, cause a human autoinflammatory disease known as familial Mediterranean fever. Despite important roles in immunity and disease, the physiological function of Pyrin remains unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in response to Rho-glucosylation activity of cytotoxin TcdB, a major virulence factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea. The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating activity. Other Rho-inactivating toxins, including FIC-domain adenylyltransferases (Vibrio parahaemolyticus VopS and Histophilus somni IbpA) and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically activate the Pyrin inflammasome in their enzymatic activity-dependent manner. These toxins all target the Rho subfamily and modify a switch-I residue. We further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome activation, both of which require the bacterial type VI secretion system (T6SS). Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B. cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to sense pathogen modification and inactivation of Rho GTPases, representing a new paradigm in mammalian innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Hao -- Yang, Jieling -- Gao, Wenqing -- Li, Lin -- Li, Peng -- Zhang, Li -- Gong, Yi-Nan -- Peng, Xiaolan -- Xi, Jianzhong Jeff -- Chen, She -- Wang, Fengchao -- Shao, Feng -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Sep 11;513(7517):237-41. doi: 10.1038/nature13449. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] National Institute of Biological Sciences, Beijing 102206, China [2]. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [3]. ; National Institute of Biological Sciences, Beijing 102206, China. ; Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China. ; 1] National Institute of Biological Sciences, Beijing 102206, China [2] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [3] National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacterial Toxins/genetics/metabolism ; Burkholderia cenocepacia/metabolism ; Caspase 1/metabolism ; Cell Line ; Clostridium difficile/metabolism ; Cytoskeletal Proteins/genetics/*metabolism ; Humans ; Immunity, Innate/genetics/*immunology ; Inflammasomes/*metabolism ; Mice ; Mice, Inbred Strains ; Mutation ; Protein Binding ; Receptors, Pattern Recognition/metabolism ; U937 Cells ; rho GTP-Binding Proteins/*metabolism
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jan 23;505(7484):453.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24459716" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; Cloning, Organism/history ; Embryonic Stem Cells/cytology ; History, 20th Century ; History, 21st Century ; Humans ; Patents as Topic/ethics/legislation & jurisprudence ; *Public Opinion ; Republic of Korea ; Research Personnel/*ethics/history/standards ; Retraction of Publication as Topic ; *Scientific Misconduct/history ; Trust ; Whistleblowing
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  • 65
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanson, Jim -- England -- Nature. 2014 Feb 6;506(7486):35. doi: 10.1038/506035a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Sussex, Brighton, UK. He worked in the same laboratory as John Cornforth for three decades.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499912" target="_blank"〉PubMed〈/a〉
    Keywords: Australia ; Chemistry/*history ; Cholesterol/*biosynthesis/chemistry ; Fatty Acids/biosynthesis ; Great Britain ; History, 20th Century ; Nobel Prize ; Oxazolone/chemistry ; Penicillins/chemistry/metabolism ; Persons With Hearing Impairments/history ; Steroids/chemical synthesis
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2014-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2014 Jun 12;510(7504):195-6. doi: 10.1038/510195a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919900" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic ; Dopaminergic Neurons/*cytology/transplantation ; *Fetal Tissue Transplantation/history ; History, 20th Century ; Humans ; Parkinson Disease/*pathology/*surgery ; Retrospective Studies ; Stem Cell Transplantation ; Stem Cells/cytology
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  • 67
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    Publication Date: 2014-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2014 May 1;509(7498):22-4. doi: 10.1038/509022a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24784198" target="_blank"〉PubMed〈/a〉
    Keywords: Centers for Disease Control and Prevention (U.S.) ; DNA, Viral/analysis/isolation & purification ; *Disease Eradication/statistics & numerical data ; Evolution, Molecular ; Female ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Male ; Mummies/*virology ; Smallpox/epidemiology/*history/transmission/*virology ; Smallpox Vaccine/history ; Time Factors ; United States ; Variola virus/genetics/*isolation & purification
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  • 68
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    Publication Date: 2014-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steiner, Lisa -- Ploegh, Hidde -- England -- Nature. 2014 Dec 4;516(7529):38. doi: 10.1038/516038a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, USA. She worked under Herman Eisen as a postdoctoral researcher between 1962 and 1965, and they were friends for more than 50 years. ; MIT, and worked with Eisen at the MIT Center for Cancer Research from 1992.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25471875" target="_blank"〉PubMed〈/a〉
    Keywords: Allergy and Immunology/*history ; Antibodies/immunology ; History, 20th Century ; History, 21st Century ; Receptors, Antigen, T-Cell/immunology
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  • 69
    Publication Date: 2014-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clayton, Janine A -- Collins, Francis S -- England -- Nature. 2014 May 15;509(7500):282-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24834516" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Experimentation/standards ; Animals ; Animals, Laboratory ; Biomedical Research/economics/*methods/standards ; Cell Line ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Financing, Organized/organization & administration ; Humans ; Male ; Multiple Sclerosis/drug therapy/pathology ; *National Institutes of Health (U.S.)/economics ; Neurons/cytology/drug effects/pathology ; Peer Review, Research/standards ; *Research Design/standards ; *Sex Characteristics ; *Sex Ratio ; Substance-Related Disorders/drug therapy/physiopathology ; United States
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  • 70
    Publication Date: 2014-06-05
    Description: Cells maintain healthy mitochondria by degrading damaged mitochondria through mitophagy; defective mitophagy is linked to Parkinson's disease. Here we report that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy driven by the ubiquitin ligase parkin (also known as PARK2) and protein kinase PINK1, which are encoded by two genes associated with Parkinson's disease. Parkin ubiquitinates and tags damaged mitochondria for clearance. Overexpression of USP30 removes ubiquitin attached by parkin onto damaged mitochondria and blocks parkin's ability to drive mitophagy, whereas reducing USP30 activity enhances mitochondrial degradation in neurons. Global ubiquitination site profiling identified multiple mitochondrial substrates oppositely regulated by parkin and USP30. Knockdown of USP30 rescues the defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin- or PINK1-deficient flies. Knockdown of USP30 in dopaminergic neurons protects flies against paraquat toxicity in vivo, ameliorating defects in dopamine levels, motor function and organismal survival. Thus USP30 inhibition is potentially beneficial for Parkinson's disease by promoting mitochondrial clearance and quality control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bingol, Baris -- Tea, Joy S -- Phu, Lilian -- Reichelt, Mike -- Bakalarski, Corey E -- Song, Qinghua -- Foreman, Oded -- Kirkpatrick, Donald S -- Sheng, Morgan -- England -- Nature. 2014 Jun 19;510(7505):370-5. doi: 10.1038/nature13418. Epub 2014 Jun 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA [2]. ; Department of Protein Chemistry, Genentech, Inc., South San Francisco, California 94080, USA. ; Department of Pathology, Genentech, Inc., South San Francisco, California 94080, USA. ; Department of Bioinformatics & Computational Biology, Genentech, Inc., South San Francisco, California 94080, USA. ; Department of Non-Clinical Biostatistics, Genentech, Inc., South San Francisco, California 94080, USA. ; Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896179" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; Drosophila melanogaster/genetics/metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; HeLa Cells ; Humans ; Male ; Mitochondrial Degradation/*physiology ; Mitochondrial Proteins/genetics/*metabolism ; Neurons/metabolism ; Parkinson Disease/physiopathology ; Protein Kinases/metabolism ; Rats ; Thiolester Hydrolases/genetics/*metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitin-Specific Proteases/genetics/metabolism ; Ubiquitination
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  • 71
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, David -- England -- Nature. 2014 Jan 9;505(7482):153-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24409511" target="_blank"〉PubMed〈/a〉
    Keywords: Cooperative Behavior ; History, 20th Century ; History, 21st Century ; Interdisciplinary Communication ; Physics ; Research/economics/*history/*organization & administration/trends ; Research Support as Topic/economics/history/trends ; United States ; World War II
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  • 72
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Birnbaum, Morris -- Gewin, Virginia -- England -- Nature. 2014 Nov 13;515(7526):301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25396247" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Mobility ; Drug Discovery ; *Drug Industry ; Education, Graduate ; Education, Medical ; History, 20th Century ; History, 21st Century ; Insulin/metabolism ; *Research Personnel/education
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  • 73
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Barry -- Azad, Meghan -- England -- Nature. 2014 Oct 16;514(7522):S6-7. doi: 10.1038/514S6a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25317594" target="_blank"〉PubMed〈/a〉
    Keywords: Helicobacter pylori/genetics/isolation & purification/*pathogenicity ; History, 20th Century ; History, 21st Century ; Human Migration ; Humans ; Hygiene Hypothesis ; Job Satisfaction ; Male ; Nobel Prize ; Reproducibility of Results ; Stomach Ulcer/*etiology/history/*microbiology ; Stress, Psychological ; Vaccines, Edible
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  • 74
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    Nature Publishing Group (NPG)
    Publication Date: 2014-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bishop, Michael -- Weiskopf, Kipp -- England -- Nature. 2014 Oct 16;514(7522):S9-10. doi: 10.1038/514S9a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25317596" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research ; California ; Computational Biology ; Drug Discovery/organization & administration/trends ; Drug Industry ; Drug Resistance, Neoplasm/genetics ; Female ; History, 20th Century ; *Neoplasms/etiology/genetics/metabolism ; Nobel Prize ; RNA-Directed DNA Polymerase/history ; Retroviridae/enzymology ; Smoking/adverse effects
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  • 75
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedman, Jeffrey -- England -- Nature. 2014 May 29;509(7502):564. doi: 10.1038/509564a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University in New York City. He was a co-recipient with Douglas Coleman of the 2010 Albert Lasker Basic Medical Research Award for the discovery of leptin.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870535" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism ; Animals ; Appetite/*genetics ; Biochemistry/*history ; Canada ; History, 20th Century ; History, 21st Century ; Leptin/genetics/metabolism ; Mice ; Mice, Obese/genetics ; Obesity/*genetics ; *Satiety Response ; United States
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  • 76
    Publication Date: 2014-04-11
    Description: Targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. In contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. Here we report the development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis. Using knockout library screens, we successfully identified the host genes essential for the intoxication of cells by anthrax and diphtheria toxins, which were confirmed by functional validation. The broad application of this powerful genetic screening strategy will not only facilitate the rapid identification of genes important for bacterial toxicity but will also enable the discovery of genes that participate in other biological processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yuexin -- Zhu, Shiyou -- Cai, Changzu -- Yuan, Pengfei -- Li, Chunmei -- Huang, Yanyi -- Wei, Wensheng -- England -- Nature. 2014 May 22;509(7501):487-91. doi: 10.1038/nature13166. Epub 2014 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China [2]. ; State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China. ; Biodynamic Optical Imaging Centre (BIOPIC), College of Engineering, Peking University, Beijing 100871, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717434" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Bacterial/pharmacology ; Bacterial Toxins/pharmacology ; CRISPR-Associated Proteins/*genetics ; Cell Line ; Cells/drug effects/*metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; Diphtheria Toxin/pharmacology ; *Gene Library ; Genomics/*methods ; High-Throughput Screening Assays/*methods ; Humans ; INDEL Mutation/genetics ; Lentivirus/genetics ; Organic Cation Transporter 1/genetics ; RNA, Guide/genetics ; Reproducibility of Results
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 77
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Insel, Thomas R -- Landis, Story -- England -- Nature. 2014 Nov 20;515(7527):344. doi: 10.1038/515344a. Epub 2014 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉US National Institute of Mental Health, Bethesda, Maryland, USA. ; US National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25409820" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biology/history ; Birds/anatomy & histology/*physiology ; History, 20th Century ; History, 21st Century ; Humans ; Models, Neurological ; Neurosciences/*history ; Psychiatry/history ; Speech/*physiology ; Vocalization, Animal/*physiology
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  • 78
    Publication Date: 2014-11-05
    Description: T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297519/" 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/PMC4297519/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Yu-Hwa -- Zhu, Chen -- Kondo, Yasuyuki -- Anderson, Ana C -- Gandhi, Amit -- Russell, Andrew -- Dougan, Stephanie K -- Petersen, Britt-Sabina -- Melum, Espen -- Pertel, Thomas -- Clayton, Kiera L -- Raab, Monika -- Chen, Qiang -- Beauchemin, Nicole -- Yazaki, Paul J -- Pyzik, Michal -- Ostrowski, Mario A -- Glickman, Jonathan N -- Rudd, Christopher E -- Ploegh, Hidde L -- Franke, Andre -- Petsko, Gregory A -- Kuchroo, Vijay K -- Blumberg, Richard S -- AI039671/AI/NIAID NIH HHS/ -- AI056299/AI/NIAID NIH HHS/ -- AI073748/AI/NIAID NIH HHS/ -- DK0034854/DK/NIDDK NIH HHS/ -- DK044319/DK/NIDDK NIH HHS/ -- DK051362/DK/NIDDK NIH HHS/ -- DK053056/DK/NIDDK NIH HHS/ -- DK088199/DK/NIDDK NIH HHS/ -- GM32415/GM/NIGMS NIH HHS/ -- MOP-93787/Canadian Institutes of Health Research/Canada -- NS045937/NS/NINDS NIH HHS/ -- P01 AI039671/AI/NIAID NIH HHS/ -- P01 AI056299/AI/NIAID NIH HHS/ -- P01 AI073748/AI/NIAID NIH HHS/ -- P30 DK034854/DK/NIDDK NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- R01 DK051362/DK/NIDDK NIH HHS/ -- R01 GM026788/GM/NIGMS NIH HHS/ -- R01 NS045937/NS/NINDS NIH HHS/ -- T32 GM007122/GM/NIGMS NIH HHS/ -- UL1 TR001102/TR/NCATS NIH HHS/ -- England -- Nature. 2015 Jan 15;517(7534):386-90. doi: 10.1038/nature13848. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA. ; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. ; Rosenstiel Basic Medical Sciences Research Center, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA. ; Whitehead Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel 24105, Germany. ; 1] Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA [2] Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo 0424, Norway. ; Department of Immunology, University of Toronto, Toronto, Ontario M5S1A8, Canada. ; Cell Signalling Section, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. ; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. ; Goodman Cancer Research Centre, McGill University, Montreal H3G 1Y6, Canada. ; Beckman Institute, City of Hope, Duarte, California 91010, USA. ; 1] Department of Immunology, University of Toronto, Toronto, Ontario M5S1A8, Canada [2] Keenan Research Centre of St. Michael's Hospital, Toronto, Ontario M5S1A8, Canada. ; GI Pathology, Miraca Life Sciences, Newton, Massachusetts 02464, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363763" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/chemistry/immunology/*metabolism ; Autoimmunity/immunology ; Cell Adhesion Molecules/chemistry/immunology/*metabolism ; Cell Line ; Colorectal Neoplasms/immunology ; Disease Models, Animal ; Female ; Humans ; Immune Tolerance/*immunology ; Inflammation/immunology/pathology ; Ligands ; Male ; Membrane Proteins/chemistry/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Molecular ; Mucous Membrane/immunology/pathology ; Protein Conformation ; Protein Multimerization ; Receptors, Virus/chemistry/immunology/*metabolism ; T-Lymphocytes/*immunology/*metabolism
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  • 79
    Publication Date: 2014-01-28
    Description: Earth system models project that the tropical land carbon sink will decrease in size in response to an increase in warming and drought during this century, probably causing a positive climate feedback. But available data are too limited at present to test the predicted changes in the tropical carbon balance in response to climate change. Long-term atmospheric carbon dioxide data provide a global record that integrates the interannual variability of the global carbon balance. Multiple lines of evidence demonstrate that most of this variability originates in the terrestrial biosphere. In particular, the year-to-year variations in the atmospheric carbon dioxide growth rate (CGR) are thought to be the result of fluctuations in the carbon fluxes of tropical land areas. Recently, the response of CGR to tropical climate interannual variability was used to put a constraint on the sensitivity of tropical land carbon to climate change. Here we use the long-term CGR record from Mauna Loa and the South Pole to show that the sensitivity of CGR to tropical temperature interannual variability has increased by a factor of 1.9 +/- 0.3 in the past five decades. We find that this sensitivity was greater when tropical land regions experienced drier conditions. This suggests that the sensitivity of CGR to interannual temperature variations is regulated by moisture conditions, even though the direct correlation between CGR and tropical precipitation is weak. We also find that present terrestrial carbon cycle models do not capture the observed enhancement in CGR sensitivity in the past five decades. More realistic model predictions of future carbon cycle and climate feedbacks require a better understanding of the processes driving the response of tropical ecosystems to drought and warming.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xuhui -- Piao, Shilong -- Ciais, Philippe -- Friedlingstein, Pierre -- Myneni, Ranga B -- Cox, Peter -- Heimann, Martin -- Miller, John -- Peng, Shushi -- Wang, Tao -- Yang, Hui -- Chen, Anping -- England -- Nature. 2014 Feb 13;506(7487):212-5. doi: 10.1038/nature12915. Epub 2014 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. ; 1] Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China [2] Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing 100085, China. ; 1] Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China [2] Laboratoire des Sciences du Climat et de l'Environnement, CEA CNRS UVSQ, 91191 Gif-sur-Yvette, France. ; College of Engineering, Mathematics, and Physical Sciences, University of Exeter, Exeter EX4 4QF, UK. ; Department of Earth and Environment, Boston University, Boston, Massachusetts 02215, USA. ; Max Planck Institute for Biogeochemistry, 07701 Jena, Germany. ; 1] Global Monitoring Division, Earth System Research Laboratory, National Oceanic and Atmospheric Administration, 325 Broadway, Boulder, Colorado 80305, USA [2] Cooperative Institute for Research in Environmental Sciences, University of Colorado, Boulder, Colorado 80309, USA. ; Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544-1003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463514" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Atmosphere/chemistry ; Carbon/analysis/metabolism ; Carbon Cycle/*physiology ; Carbon Dioxide/metabolism ; Carbon Sequestration ; Droughts ; Ecosystem ; Global Warming ; Hawaii ; History, 20th Century ; History, 21st Century ; Humidity ; Models, Theoretical ; Rain ; *Temperature ; *Tropical Climate
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  • 80
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    Nature Publishing Group (NPG)
    Publication Date: 2014-11-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Serjeant, Graham -- Mallapaty, Smriti -- England -- Nature. 2014 Nov 13;515(7526):S6-7. doi: 10.1038/515S6a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25390144" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; *Anemia, Sickle Cell/epidemiology/genetics/prevention & control/therapy ; Biomedical Research/history ; Charities/history ; Cohort Studies ; Genetic Counseling ; Global Health ; History, 20th Century ; History, 21st Century ; Humans ; Infant, Newborn ; Internationality ; Jamaica ; Neonatal Screening ; Quality of Life ; Young Adult
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  • 81
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    Publication Date: 2014-03-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Mar 20;507(7492):274.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24654277" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/history ; Archives ; History, 20th Century ; Periodicals as Topic ; Research/*history ; Research Personnel/*history/psychology
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  • 82
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    Nature Publishing Group (NPG)
    Publication Date: 2014-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, Jane E -- England -- Nature. 2014 Apr 10;508(7495):187. doi: 10.1038/508187a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Intel. She was an employee of ALZA from 1970 to 1994 and served as president and chief operating officer from 1989 to 1994.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717508" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Inhalation ; Biotechnology/*history ; Combinatorial Chemistry Techniques/history ; Delayed-Action Preparations/history ; Drug Delivery Systems/*history ; Drug Discovery/history ; Drug Industry/*history ; Entrepreneurship/history ; Genome-Wide Association Study/history ; History, 20th Century ; History, 21st Century ; Humans ; Oligonucleotide Array Sequence Analysis/history ; Steroids/history ; Transdermal Patch/history ; United States ; Uruguay
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2014-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Druker, Brian J -- England -- Nature. 2014 Jan 23;505(7484):484. doi: 10.1038/505484a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Knight Cancer Institute at Oregon Health & Science University, Portland, Oregon, and a Howard Hughes Medical Institute investigator. He shared the 2012 Japan Prize with Janet Rowley and Nicholas Lydon.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24451535" target="_blank"〉PubMed〈/a〉
    Keywords: Benzamides/therapeutic use ; Genetics, Medical/*history ; History, 20th Century ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics/pathology ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Promyelocytic, Acute/drug therapy/genetics ; Neoplasms/*genetics/history ; Piperazines/therapeutic use ; Pyrimidines/therapeutic use ; Translocation, Genetic/*genetics ; United States
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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2014-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Briggs, Derek E G -- England -- Nature. 2014 May 22;509(7501):428. doi: 10.1038/509428a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Peabody Museum of Natural History at Yale University in New Haven, Connecticut, USA. He taught with Dolf Seilacher at Yale from 2003 to 2009.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24848054" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Fossils ; Germany ; History, 20th Century ; History, 21st Century ; Paleontology/*history
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  • 85
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    Publication Date: 2014-07-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferry, Georgina -- England -- Nature. 2014 Jul 10;511(7508):150-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013879" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; History, 20th Century ; History, 21st Century ; Periodicals as Topic ; Research/economics/standards/statistics & numerical data ; Societies/*history/standards/trends
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  • 86
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    Nature Publishing Group (NPG)
    Publication Date: 2014-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferry, Georgina -- England -- Nature. 2014 Jan 30;505(7485):609-11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24482834" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallography, X-Ray/*history ; History, 20th Century ; History, 21st Century ; Nobel Prize ; Research Personnel/*history ; Sexism/history ; Women's Rights/*history/statistics & numerical data
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  • 87
    Publication Date: 2014-09-12
    Description: Genetic equality between males and females is established by chromosome-wide dosage-compensation mechanisms. In the fruitfly Drosophila melanogaster, the dosage-compensation complex promotes twofold hypertranscription of the single male X-chromosome and is silenced in females by inhibition of the translation of msl2, which codes for the limiting component of the dosage-compensation complex. The female-specific protein Sex-lethal (Sxl) recruits Upstream-of-N-ras (Unr) to the 3' untranslated region of msl2 messenger RNA, preventing the engagement of the small ribosomal subunit. Here we report the 2.8 A crystal structure, NMR and small-angle X-ray and neutron scattering data of the ternary Sxl-Unr-msl2 ribonucleoprotein complex featuring unprecedented intertwined interactions of two Sxl RNA recognition motifs, a Unr cold-shock domain and RNA. Cooperative complex formation is associated with a 1,000-fold increase of RNA binding affinity for the Unr cold-shock domain and involves novel ternary interactions, as well as non-canonical RNA contacts by the alpha1 helix of Sxl RNA recognition motif 1. Our results suggest that repression of dosage compensation, necessary for female viability, is triggered by specific, cooperative molecular interactions that lock a ribonucleoprotein switch to regulate translation. The structure serves as a paradigm for how a combination of general and widespread RNA binding domains expands the code for specific single-stranded RNA recognition in the regulation of gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hennig, Janosch -- Militti, Cristina -- Popowicz, Grzegorz M -- Wang, Iren -- Sonntag, Miriam -- Geerlof, Arie -- Gabel, Frank -- Gebauer, Fatima -- Sattler, Michael -- England -- Nature. 2014 Nov 13;515(7526):287-90. doi: 10.1038/nature13693. Epub 2014 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Structural Biology, Helmholtz Zentrum Munchen, Ingolstadter Landstrasse 1, DE-85764, Germany [2] Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universitat Munchen, Lichtenbergstr. 4, DE-85747 Garching, Germany. ; 1] Centre for Genomic Regulation, Gene Regulation, Stem Cells and Cancer Programme, Dr Aiguader 88, 08003 Barcelona, Spain [2] Universisty Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain. ; Institute of Structural Biology, Helmholtz Zentrum Munchen, Ingolstadter Landstrasse 1, DE-85764, Germany. ; 1] Universite Grenoble Alpes, Institut de Biologie Structurale, F-38044 Grenoble, France [2] Centre National de la Recherche Scientifique, Institut de Biologie Structurale, F-38044 Grenoble, France [3] Commissariat a l'Energie Atomique et aux Energies Alternatives, Institut de Biologie Structurale, F-38044 Grenoble, France [4] Institut Laue-Langevin, F-38042 Grenoble, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Cold-Shock Response ; Crystallography, X-Ray ; DNA-Binding Proteins/*chemistry/*metabolism ; Dosage Compensation, Genetic ; Drosophila Proteins/*chemistry/*metabolism ; Drosophila melanogaster/*chemistry/genetics ; Female ; Gene Expression Regulation ; Male ; Models, Molecular ; Neutron Diffraction ; Nuclear Magnetic Resonance, Biomolecular ; Nucleotide Motifs ; *Protein Biosynthesis ; Protein Structure, Tertiary ; RNA, Messenger/chemistry/*metabolism ; RNA-Binding Proteins/*chemistry/*metabolism ; Ribonucleoproteins/chemistry/metabolism ; Scattering, Small Angle ; Structure-Activity Relationship ; X-Ray Diffraction
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 88
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halyo, Valerie -- England -- Nature. 2014 Dec 18;516(7531):330. doi: 10.1038/516330a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Princeton University, New Jersey, USA. She earned her PhD under the supervision of Martin L. Perl at Stanford University in California from 1997 to 2001.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25519123" target="_blank"〉PubMed〈/a〉
    Keywords: Elementary Particles ; History, 20th Century ; Michigan ; New York ; Nobel Prize ; *Physics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 89
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" 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/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 90
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Jan 9;505(7482):132.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24409510" target="_blank"〉PubMed〈/a〉
    Keywords: History, 20th Century ; Military Science ; Research Support as Topic ; *Science/economics/organization & administration ; *Warfare ; World War I ; World War II
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 91
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2014 Sep 4;513(7516):16-7. doi: 10.1038/513016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186880" target="_blank"〉PubMed〈/a〉
    Keywords: Disaster Planning/*trends ; Earthquakes/history/mortality/*statistics & numerical data ; History, 17th Century ; History, 19th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; *Lakes ; Switzerland ; Tsunamis/history/*statistics & numerical data
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 92
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nadin, Mihai -- England -- Nature. 2014 Nov 6;515(7525):37. doi: 10.1038/515037c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Research in Anticipatory Systems, University of Texas at Dallas, Richardson, Texas, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dogs ; Georgia (Republic) ; History, 20th Century ; Neurophysiology/*history ; Nobel Prize ; Orientation/physiology ; Space Perception/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 93
    Publication Date: 2014-08-29
    Description: Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227084/" 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/PMC4227084/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, Joshua W K -- Jung, Youngsook L -- Liu, Tao -- Alver, Burak H -- Lee, Soohyun -- Ikegami, Kohta -- Sohn, Kyung-Ah -- Minoda, Aki -- Tolstorukov, Michael Y -- Appert, Alex -- Parker, Stephen C J -- Gu, Tingting -- Kundaje, Anshul -- Riddle, Nicole C -- Bishop, Eric -- Egelhofer, Thea A -- Hu, Sheng'en Shawn -- Alekseyenko, Artyom A -- Rechtsteiner, Andreas -- Asker, Dalal -- Belsky, Jason A -- Bowman, Sarah K -- Chen, Q Brent -- Chen, Ron A-J -- Day, Daniel S -- Dong, Yan -- Dose, Andrea C -- Duan, Xikun -- Epstein, Charles B -- Ercan, Sevinc -- Feingold, Elise A -- Ferrari, Francesco -- Garrigues, Jacob M -- Gehlenborg, Nils -- Good, Peter J -- Haseley, Psalm -- He, Daniel -- Herrmann, Moritz -- Hoffman, Michael M -- Jeffers, Tess E -- Kharchenko, Peter V -- Kolasinska-Zwierz, Paulina -- Kotwaliwale, Chitra V -- Kumar, Nischay -- Langley, Sasha A -- Larschan, Erica N -- Latorre, Isabel -- Libbrecht, Maxwell W -- Lin, Xueqiu -- Park, Richard -- Pazin, Michael J -- Pham, Hoang N -- Plachetka, Annette -- Qin, Bo -- Schwartz, Yuri B -- Shoresh, Noam -- Stempor, Przemyslaw -- Vielle, Anne -- Wang, Chengyang -- Whittle, Christina M -- Xue, Huiling -- Kingston, Robert E -- Kim, Ju Han -- Bernstein, Bradley E -- Dernburg, Abby F -- Pirrotta, Vincenzo -- Kuroda, Mitzi I -- Noble, William S -- Tullius, Thomas D -- Kellis, Manolis -- MacAlpine, David M -- Strome, Susan -- Elgin, Sarah C R -- Liu, Xiaole Shirley -- Lieb, Jason D -- Ahringer, Julie -- Karpen, Gary H -- Park, Peter J -- 092096/Wellcome Trust/United Kingdom -- 101863/Wellcome Trust/United Kingdom -- 54523/Wellcome Trust/United Kingdom -- 5RL9EB008539/EB/NIBIB NIH HHS/ -- K99 HG006259/HG/NHGRI NIH HHS/ -- K99HG006259/HG/NHGRI NIH HHS/ -- R01 GM098461/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R37 GM048405/GM/NIGMS NIH HHS/ -- T32 GM071340/GM/NIGMS NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U01 HG004258/HG/NHGRI NIH HHS/ -- U01 HG004270/HG/NHGRI NIH HHS/ -- U01 HG004279/HG/NHGRI NIH HHS/ -- U01 HG004695/HG/NHGRI NIH HHS/ -- U01HG004258/HG/NHGRI NIH HHS/ -- U01HG004270/HG/NHGRI NIH HHS/ -- U01HG004279/HG/NHGRI NIH HHS/ -- U01HG004695/HG/NHGRI NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 HG004570/HG/NHGRI NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- U54CA121852/CA/NCI NIH HHS/ -- U54HG004570/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 28;512(7515):449-52. doi: 10.1038/nature13415.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] [4] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3]. ; 1] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] [4] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Department of Information and Computer Engineering, Ajou University, Suwon 443-749, Korea [2] Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. ; 1] National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA [2] National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA [3] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA [2] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA. ; Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA [2] Food Science and Technology Department, Faculty of Agriculture, Alexandria University, 21545 El-Shatby, Alexandria, Egypt. ; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard/MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA. ; Department of Anatomy Physiology and Cell Biology, University of California Davis, Davis, California 95616, USA. ; Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA. ; National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. ; Princess Margaret Cancer Centre, Toronto, Ontario M6G 1L7, Canada. ; 1] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. ; Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA. ; Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA [2] Department of Molecular Biology, Umea University, 901 87 Umea, Sweden. ; 1] Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea [2] Seoul National University Biomedical Informatics, Division of Biomedical Informatics, College of Medicine, Seoul National University, Seoul 110-799, Korea. ; 1] Broad Institute, Cambridge, Massachusetts 02141, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA [3] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA. ; 1] Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; 1] Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA [2] Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA. ; 1] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Informatics Program, Children's Hospital, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164756" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*cytology/*genetics ; Cell Line ; Centromere/genetics/metabolism ; Chromatin/chemistry/*genetics/*metabolism ; Chromatin Assembly and Disassembly/genetics ; DNA Replication/genetics ; Drosophila melanogaster/*cytology/*genetics ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic ; Heterochromatin/chemistry/genetics/metabolism ; Histones/chemistry/metabolism ; Humans ; Molecular Sequence Annotation ; Nuclear Lamina/metabolism ; Nucleosomes/chemistry/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 94
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-08-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nottebohm, Fernando -- England -- Nature. 2014 Aug 28;512(7515):372. doi: 10.1038/512372a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University in New York, USA. He earned his PhD under Peter Marler at the University of California, Berkeley, in the 1960s.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164741" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Communication ; Animals ; Female ; Great Britain ; History, 20th Century ; Humans ; Language ; Learning/physiology ; Male ; Primates/physiology ; Songbirds/*physiology ; United States
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 95
    Publication Date: 2014-09-05
    Description: The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) 〈50 mug ml(-1). The median IC50 of neutralized viruses was 0.033 mug ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224615/" 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/PMC4224615/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jinghe -- Kang, Byong H -- Pancera, Marie -- Lee, Jeong Hyun -- Tong, Tommy -- Feng, Yu -- Imamichi, Hiromi -- Georgiev, Ivelin S -- Chuang, Gwo-Yu -- Druz, Aliaksandr -- Doria-Rose, Nicole A -- Laub, Leo -- Sliepen, Kwinten -- van Gils, Marit J -- de la Pena, Alba Torrents -- Derking, Ronald -- Klasse, Per-Johan -- Migueles, Stephen A -- Bailer, Robert T -- Alam, Munir -- Pugach, Pavel -- Haynes, Barton F -- Wyatt, Richard T -- Sanders, Rogier W -- Binley, James M -- Ward, Andrew B -- Mascola, John R -- Kwong, Peter D -- Connors, Mark -- 280829/European Research Council/International -- AI84714/AI/NIAID NIH HHS/ -- AI93278/AI/NIAID NIH HHS/ -- P01 AI082362/AI/NIAID NIH HHS/ -- R01 AI100790/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- ZIA AI000855-15/Intramural NIH HHS/ -- ZIA AI001090-05/Intramural NIH HHS/ -- England -- Nature. 2014 Nov 6;515(7525):138-42. doi: 10.1038/nature13601. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] The Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [2] International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; San Diego Biomedical Research Institute, San Diego, California 92121, USA. ; International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1100 DD, The Netherlands. ; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA. ; Duke Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA. ; 1] Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1100 DD, The Netherlands [2] Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186731" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Antibodies, Monoclonal/chemistry/genetics/immunology/pharmacology ; Antibodies, Neutralizing/chemistry/genetics/*immunology/pharmacology ; *Antibody Affinity ; Antibody Specificity ; Antigens, CD4/metabolism ; Cell Line ; Cell Membrane/virology ; Conserved Sequence ; Epitope Mapping ; Epitopes/chemistry/immunology ; HIV Antibodies/chemistry/genetics/*immunology/pharmacology ; HIV Envelope Protein gp120/*chemistry/*immunology ; HIV Envelope Protein gp41/*chemistry/*immunology ; HIV-1/drug effects/immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/genetics/immunology/ultrastructure ; Inhibitory Concentration 50 ; Leukocytes, Mononuclear ; Models, Molecular ; Molecular Sequence Data ; Receptors, CCR5/metabolism ; Virus Internalization/drug effects
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 96
    Publication Date: 2014-09-05
    Description: Rainfall on Earth is most intense in the intertropical convergence zone (ITCZ), a narrow belt of clouds centred on average around six degrees north of the Equator. The mean position of the ITCZ north of the Equator arises primarily because the Atlantic Ocean transports energy northward across the Equator, rendering the Northern Hemisphere warmer than the Southern Hemisphere. On seasonal and longer timescales, the ITCZ migrates, typically towards a warming hemisphere but with exceptions, such as during El Nino events. An emerging framework links the ITCZ to the atmospheric energy balance and may account for ITCZ variations on timescales from years to geological epochs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schneider, Tapio -- Bischoff, Tobias -- Haug, Gerald H -- England -- Nature. 2014 Sep 4;513(7516):45-53. doi: 10.1038/nature13636.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] California Institute of Technology, Pasadena, California 91125, USA [2] Department of Earth Sciences, ETH Zurich, 8092 Zurich, Switzerland. ; Department of Earth Sciences, ETH Zurich, 8092 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186899" target="_blank"〉PubMed〈/a〉
    Keywords: Arctic Regions ; Atlantic Ocean ; *Atmosphere ; El Nino-Southern Oscillation/history ; Feedback ; History, 20th Century ; History, Ancient ; Ice Cover ; Models, Theoretical ; *Motion ; Pacific Ocean ; *Rain ; Seasons ; *Temperature ; *Tropical Climate ; Wind
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2014-09-26
    Description: Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication and DNA damage repair. The identification of new histone modifications critical for transcriptional regulation at initiation, elongation or termination is of particular interest. Here we report a new layer of regulation in transcriptional elongation that is conserved from yeast to mammals. This regulation is based on the phosphorylation of a highly conserved tyrosine residue, Tyr 57, in histone H2A and is mediated by the unsuspected tyrosine kinase activity of casein kinase 2 (CK2). Mutation of Tyr 57 in H2A in yeast or inhibition of CK2 activity impairs transcriptional elongation in yeast as well as in mammalian cells. Genome-wide binding analysis reveals that CK2alpha, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers. Mutation of Tyr 57 causes a loss of H2B mono-ubiquitination as well as H3K4me3 and H3K79me3, histone marks associated with active transcription. Mechanistically, both CK2 inhibition and the H2A(Y57F) mutation enhance H2B deubiquitination activity of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, suggesting a critical role of this phosphorylation in coordinating the activity of the SAGA complex during transcription. Together, these results identify a new component of regulation in transcriptional elongation based on CK2-dependent tyrosine phosphorylation of the globular domain of H2A.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461219/" 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/PMC4461219/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Basnet, Harihar -- Su, Xue B -- Tan, Yuliang -- Meisenhelder, Jill -- Merkurjev, Daria -- Ohgi, Kenneth A -- Hunter, Tony -- Pillus, Lorraine -- Rosenfeld, Michael G -- CA173903/CA/NCI NIH HHS/ -- CA82683/CA/NCI NIH HHS/ -- DK018477/DK/NIDDK NIH HHS/ -- DK039949/DK/NIDDK NIH HHS/ -- GM033279/GM/NIGMS NIH HHS/ -- HL065445/HL/NHLBI NIH HHS/ -- NS034934/NS/NINDS NIH HHS/ -- P30 CA023100/CA/NCI NIH HHS/ -- R01 DK018477/DK/NIDDK NIH HHS/ -- R01 GM033279/GM/NIGMS NIH HHS/ -- R01 HL065445/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- T32 DK007541/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 11;516(7530):267-71. doi: 10.1038/nature13736. Epub 2014 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Biomedical Sciences Graduate Program, School of Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Division of Biological Sciences, Section of Molecular Biology, UCSD Moores Cancer Center, University of California San Diego, La Jolla, California 92093-0347, USA. ; Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA. ; Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; 1] Howard Hughes Medical Institute, Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Bioinformatics and Systems Biology Program, Department of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25252977" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Casein Kinase II/*metabolism ; Cell Line ; Conserved Sequence ; Histones/*chemistry/genetics/*metabolism ; Humans ; Molecular Sequence Data ; Phosphorylation ; Saccharomyces cerevisiae/genetics/metabolism ; *Transcription Elongation, Genetic ; Tyrosine/chemistry/*metabolism ; Ubiquitination/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2014-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Nov 6;515(7525):7-8. doi: 10.1038/515007b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25373637" target="_blank"〉PubMed〈/a〉
    Keywords: Europe, Eastern ; European Union ; History, 20th Century ; History, 21st Century ; Science/history/*organization & administration/*trends
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2014-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2014 Oct 16;514(7522):286. doi: 10.1038/nature.2014.16097.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25318502" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Survival ; Fluorescent Dyes/analysis ; History, 20th Century ; History, 21st Century ; Lasers ; Microscopy, Fluorescence/history/*methods/trends ; Nanotechnology/methods ; *Nobel Prize ; Optics and Photonics/methods ; Quantum Theory
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2014-04-05
    Description: Damage to the central nervous system caused by traumatic injury or neurological disorders can lead to permanent loss of voluntary motor function and muscle paralysis. Here, we describe an approach that circumvents central motor circuit pathology to restore specific skeletal muscle function. We generated murine embryonic stem cell-derived motor neurons that express the light-sensitive ion channel channelrhodopsin-2, which we then engrafted into partially denervated branches of the sciatic nerve of adult mice. These engrafted motor neurons not only reinnervated lower hind-limb muscles but also enabled their function to be restored in a controllable manner using optogenetic stimulation. This synthesis of regenerative medicine and optogenetics may be a successful strategy to restore muscle function after traumatic injury or disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bryson, J Barney -- Machado, Carolina Barcellos -- Crossley, Martin -- Stevenson, Danielle -- Bros-Facer, Virginie -- Burrone, Juan -- Greensmith, Linda -- Lieberam, Ivo -- 095589/Wellcome Trust/United Kingdom -- G0900585/Medical Research Council/United Kingdom -- G1001234/Biotechnology and Biological Sciences Research Council/United Kingdom -- MR/K000608/1/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Apr 4;344(6179):94-7. doi: 10.1126/science.1248523.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24700859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cell Line ; Electric Stimulation ; Embryonic Stem Cells/cytology/physiology ; Female ; Hindlimb ; Isometric Contraction ; *Light ; Mice ; Mice, Inbred C57BL ; Motor Neurons/cytology/*physiology/*transplantation ; Muscle Denervation ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/*innervation/*physiology ; Nerve Regeneration ; *Optogenetics ; Rhodopsin/genetics/metabolism ; Sciatic Nerve/physiology ; Transfection ; Transgenes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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