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  • Humans  (1,447)
  • Nature Publishing Group (NPG)  (1,447)
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
  • Irkutsk : Ross. Akad. Nauk, Sibirskoe Otd., Inst. Zemnoj Kory
  • 2005-2009  (1,447)
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  • 1
    Publication Date: 2009-10-09
    Description: Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" 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/PMC3330748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Donald F -- Pinto, Dalila -- Redon, Richard -- Feuk, Lars -- Gokcumen, Omer -- Zhang, Yujun -- Aerts, Jan -- Andrews, T Daniel -- Barnes, Chris -- Campbell, Peter -- Fitzgerald, Tomas -- Hu, Min -- Ihm, Chun Hwa -- Kristiansson, Kati -- Macarthur, Daniel G -- Macdonald, Jeffrey R -- Onyiah, Ifejinelo -- Pang, Andy Wing Chun -- Robson, Sam -- Stirrups, Kathy -- Valsesia, Armand -- Walter, Klaudia -- Wei, John -- Wellcome Trust Case Control Consortium -- Tyler-Smith, Chris -- Carter, Nigel P -- Lee, Charles -- Scherer, Stephen W -- Hurles, Matthew E -- 077006/Z/05/Z/Wellcome Trust/United Kingdom -- 077008/Wellcome Trust/United Kingdom -- 077009/Wellcome Trust/United Kingdom -- 077014/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- GM081533/GM/NIGMS NIH HHS/ -- HG004221/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Apr 1;464(7289):704-12. doi: 10.1038/nature08516. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812545" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/genetics ; DNA Copy Number Variations/*genetics ; Gene Duplication ; Genetic Predisposition to Disease/*genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genotype ; Haplotypes/genetics ; Humans ; Mutagenesis/*genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
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  • 2
    Publication Date: 2009-12-23
    Description: Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (〈0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons (fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly (1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase (AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide new evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" 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/PMC2906123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutani, Nidhi -- Brady, Jennifer J -- Damian, Mara -- Sacco, Alessandra -- Corbel, Stephane Y -- Blau, Helen M -- AG009521/AG/NIA NIH HHS/ -- AG024987/AG/NIA NIH HHS/ -- AI007328/AI/NIAID NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG024987/AG/NIA NIH HHS/ -- R01 AG024987-05/AG/NIA NIH HHS/ -- T32 AI007328/AI/NIAID NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1042-7. doi: 10.1038/nature08752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20027182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Fusion ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; Chromatin Immunoprecipitation ; Cytidine Deaminase/deficiency/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; DNA Replication ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/*cytology/enzymology/*metabolism ; Lung/cytology/embryology ; Mice ; Models, Biological ; Octamer Transcription Factor-3/genetics ; Promoter Regions, Genetic/genetics ; 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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  • 3
    Publication Date: 2009-12-17
    Description: Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951497/" 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/PMC3951497/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ruiqiang -- Fan, Wei -- Tian, Geng -- Zhu, Hongmei -- He, Lin -- Cai, Jing -- Huang, Quanfei -- Cai, Qingle -- Li, Bo -- Bai, Yinqi -- Zhang, Zhihe -- Zhang, Yaping -- Wang, Wen -- Li, Jun -- Wei, Fuwen -- Li, Heng -- Jian, Min -- Li, Jianwen -- Zhang, Zhaolei -- Nielsen, Rasmus -- Li, Dawei -- Gu, Wanjun -- Yang, Zhentao -- Xuan, Zhaoling -- Ryder, Oliver A -- Leung, Frederick Chi-Ching -- Zhou, Yan -- Cao, Jianjun -- Sun, Xiao -- Fu, Yonggui -- Fang, Xiaodong -- Guo, Xiaosen -- Wang, Bo -- Hou, Rong -- Shen, Fujun -- Mu, Bo -- Ni, Peixiang -- Lin, Runmao -- Qian, Wubin -- Wang, Guodong -- Yu, Chang -- Nie, Wenhui -- Wang, Jinhuan -- Wu, Zhigang -- Liang, Huiqing -- Min, Jiumeng -- Wu, Qi -- Cheng, Shifeng -- Ruan, Jue -- Wang, Mingwei -- Shi, Zhongbin -- Wen, Ming -- Liu, Binghang -- Ren, Xiaoli -- Zheng, Huisong -- Dong, Dong -- Cook, Kathleen -- Shan, Gao -- Zhang, Hao -- Kosiol, Carolin -- Xie, Xueying -- Lu, Zuhong -- Zheng, Hancheng -- Li, Yingrui -- Steiner, Cynthia C -- Lam, Tommy Tsan-Yuk -- Lin, Siyuan -- Zhang, Qinghui -- Li, Guoqing -- Tian, Jing -- Gong, Timing -- Liu, Hongde -- Zhang, Dejin -- Fang, Lin -- Ye, Chen -- Zhang, Juanbin -- Hu, Wenbo -- Xu, Anlong -- Ren, Yuanyuan -- Zhang, Guojie -- Bruford, Michael W -- Li, Qibin -- Ma, Lijia -- Guo, Yiran -- An, Na -- Hu, Yujie -- Zheng, Yang -- Shi, Yongyong -- Li, Zhiqiang -- Liu, Qing -- Chen, Yanling -- Zhao, Jing -- Qu, Ning -- Zhao, Shancen -- Tian, Feng -- Wang, Xiaoling -- Wang, Haiyin -- Xu, Lizhi -- Liu, Xiao -- Vinar, Tomas -- Wang, Yajun -- Lam, Tak-Wah -- Yiu, Siu-Ming -- Liu, Shiping -- Zhang, Hemin -- Li, Desheng -- Huang, Yan -- Wang, Xia -- Yang, Guohua -- Jiang, Zhi -- Wang, Junyi -- Qin, Nan -- Li, Li -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Wong, Gane Ka-Shu -- Olson, Maynard -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):311-7. doi: 10.1038/nature08696. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010809" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; China ; Conserved Sequence/genetics ; Contig Mapping ; Diet/veterinary ; Dogs ; Evolution, Molecular ; Female ; Fertility/genetics/physiology ; Genome/*genetics ; *Genomics ; Heterozygote ; Humans ; Multigene Family/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Synteny/genetics ; Ursidae/classification/*genetics/physiology
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  • 4
    Publication Date: 2009-12-18
    Description: All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145108/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pleasance, Erin D -- Cheetham, R Keira -- Stephens, Philip J -- McBride, David J -- Humphray, Sean J -- Greenman, Chris D -- Varela, Ignacio -- Lin, Meng-Lay -- Ordonez, Gonzalo R -- Bignell, Graham R -- Ye, Kai -- Alipaz, Julie -- Bauer, Markus J -- Beare, David -- Butler, Adam -- Carter, Richard J -- Chen, Lina -- Cox, Anthony J -- Edkins, Sarah -- Kokko-Gonzales, Paula I -- Gormley, Niall A -- Grocock, Russell J -- Haudenschild, Christian D -- Hims, Matthew M -- James, Terena -- Jia, Mingming -- Kingsbury, Zoya -- Leroy, Catherine -- Marshall, John -- Menzies, Andrew -- Mudie, Laura J -- Ning, Zemin -- Royce, Tom -- Schulz-Trieglaff, Ole B -- Spiridou, Anastassia -- Stebbings, Lucy A -- Szajkowski, Lukasz -- Teague, Jon -- Williamson, David -- Chin, Lynda -- Ross, Mark T -- Campbell, Peter J -- Bentley, David R -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jan 14;463(7278):191-6. doi: 10.1038/nature08658. Epub 2009 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016485" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Mutational Analysis ; DNA Repair/genetics ; Gene Dosage/genetics ; Genes, Neoplasm/*genetics ; Genome, Human/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Male ; Melanoma/etiology/genetics ; MicroRNAs/genetics ; Mutagenesis, Insertional/genetics ; Mutation/*genetics ; Neoplasms/etiology/*genetics ; Polymorphism, Single Nucleotide/genetics ; Precision Medicine ; Sequence Deletion/genetics ; Ultraviolet Rays
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  • 5
    Publication Date: 2009-12-22
    Description: Broken chromosomes arising from DNA double-strand breaks result from endogenous events such as the production of reactive oxygen species during cellular metabolism, as well as from exogenous sources such as ionizing radiation. Left unrepaired or incorrectly repaired they can lead to genomic changes that may result in cell death or cancer. DNA-dependent protein kinase (DNA-PK), a holoenzyme that comprises the DNA-PK catalytic subunit (DNA-PKcs) and the heterodimer Ku70/Ku80, has a major role in non-homologous end joining-the main pathway in mammals used to repair double-strand breaks. DNA-PKcs is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids and belonging to the phosphatidylinositol-3-OH kinase (PI(3)K)-related protein family. DNA-PKcs is involved in the sensing and transmission of DNA damage signals to proteins such as p53, setting off events that lead to cell cycle arrest. It phosphorylates a wide range of substrates in vitro, including Ku70/Ku80, which is translocated along DNA. Here we present the crystal structure of human DNA-PKcs at 6.6 A resolution, in which the overall fold is clearly visible, to our knowledge, for the first time. The many alpha-helical HEAT repeats (helix-turn-helix motifs) facilitate bending and allow the polypeptide chain to fold into a hollow circular structure. The carboxy-terminal kinase domain is located on top of this structure, and a small HEAT repeat domain that probably binds DNA is inside. The structure provides a flexible cradle to promote DNA double-strand-break repair.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811870/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sibanda, Bancinyane L -- Chirgadze, Dimitri Y -- Blundell, Tom L -- 079281/Wellcome Trust/United Kingdom -- A3846/Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jan 7;463(7277):118-21. doi: 10.1038/nature08648. Epub 2009 Dec 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Cambridge, Old Addenbrooke's site, 80 Tennis Court Road, Cambridge CB2 1GA, UK. lynn@cryst.bioc.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20023628" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Nuclear/chemistry ; Catalytic Domain ; Crystallography, X-Ray ; DNA/metabolism ; DNA Breaks, Double-Stranded ; DNA-Activated Protein Kinase/*chemistry/metabolism ; DNA-Binding Proteins/chemistry ; HeLa Cells ; *Helix-Turn-Helix Motifs ; Humans ; Models, Molecular ; Nuclear Proteins/*chemistry/metabolism ; Protein Folding ; Protein Structure, Secondary
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  • 6
    Publication Date: 2009-12-17
    Description: Recent research on changing fears has examined targeting reconsolidation. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Here we introduce a non-invasive technique to target the reconsolidation of fear memories in humans. We provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640262/" 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/PMC3640262/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schiller, Daniela -- Monfils, Marie-H -- Raio, Candace M -- Johnson, David C -- Ledoux, Joseph E -- Phelps, Elizabeth A -- K05 MH067048/MH/NIMH NIH HHS/ -- P50 MH058911/MH/NIMH NIH HHS/ -- R01 MH038774/MH/NIMH NIH HHS/ -- R01 MH046516/MH/NIMH NIH HHS/ -- R21 MH072279/MH/NIMH NIH HHS/ -- R37 MH038774/MH/NIMH NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Jan 7;463(7277):49-53. doi: 10.1038/nature08637. Epub 2009 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Science, New York University, New York, New York 10003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010606" target="_blank"〉PubMed〈/a〉
    Keywords: Conditioning, Classical/*physiology ; Cues ; Electrodes ; Electroshock ; Extinction, Psychological/*physiology ; Fear/*physiology/*psychology ; Humans ; Memory/*physiology ; Models, Neurological ; Models, Psychological ; Neuronal Plasticity/*physiology ; Photic Stimulation ; Time Factors
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  • 7
    Publication Date: 2009-01-14
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340503/" 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/PMC4340503/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, Bernard T -- McCoy, Airlie J -- Spate, Kira -- Miller, Sharon E -- Evans, Philip R -- Honing, Stefan -- Owen, David J -- 090909/Wellcome Trust/United Kingdom -- MC_U105178845/Medical Research Council/United Kingdom -- England -- Nature. 2008 Dec 18;456(7224):976-79. doi: 10.1038/nature07422.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19140243" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex 2/*chemistry/genetics/*metabolism ; Amino Acid Motifs ; Animals ; Antigens, CD4/*chemistry/*metabolism ; Binding Sites ; Conserved Sequence ; *Endocytosis ; Humans ; Leucine/*metabolism ; Mice ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Subunits/chemistry/genetics/metabolism ; Rats
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  • 8
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sukhdev, Pavan -- England -- Nature. 2009 Nov 19;462(7271):277. doi: 10.1038/462277a. Epub 2009 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Economics of Ecosystems and Biodiversity (TEEB) project, United Nations Campus, Hermann-Ehlers-Strasse 10, 53113 Bonn, Germany. teeb@unep-teeb.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19915547" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; *Conservation of Natural Resources ; Fresh Water ; Government ; Humans ; Poverty
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  • 9
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Apr 23;458(7241):945-6. doi: 10.1038/458945b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396090" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollution/prevention & control ; Environmental Monitoring/*legislation & jurisprudence ; *Federal Government ; *Greenhouse Effect ; Humans ; Public Health/*legislation & jurisprudence ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence
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  • 10
    Publication Date: 2009-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katzek, Jens A -- England -- Nature. 2009 Oct 15;461(7266):875. doi: 10.1038/461875a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829352" target="_blank"〉PubMed〈/a〉
    Keywords: *Biotechnology/manpower/standards ; *Communication ; *Food, Genetically Modified/adverse effects/standards ; Humans ; Lobbying ; Oryza/metabolism ; Plants, Genetically Modified/adverse effects ; *Public Opinion ; *Research Personnel ; beta Carotene/administration & dosage/metabolism
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  • 11
    Publication Date: 2009-06-02
    Description: The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720823/" 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/PMC2720823/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raya, Angel -- Rodriguez-Piza, Ignasi -- Guenechea, Guillermo -- Vassena, Rita -- Navarro, Susana -- Barrero, Maria Jose -- Consiglio, Antonella -- Castella, Maria -- Rio, Paula -- Sleep, Eduard -- Gonzalez, Federico -- Tiscornia, Gustavo -- Garreta, Elena -- Aasen, Trond -- Veiga, Anna -- Verma, Inder M -- Surralles, Jordi -- Bueren, Juan -- Izpisua Belmonte, Juan Carlos -- R01 HL053670/HL/NHLBI NIH HHS/ -- R01 HL053670-14/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Jul 2;460(7251):53-9. doi: 10.1038/nature08129. Epub 2009 May 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19483674" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cellular Reprogramming ; Fanconi Anemia/*pathology/*therapy ; Health ; Hematopoietic Stem Cells/*cytology/metabolism ; Humans ; Pluripotent Stem Cells/*cytology/metabolism
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  • 12
    Publication Date: 2009-05-05
    Description: A20 is a negative regulator of the NF-kappaB pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation. It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-kappaB in response to a variety of external stimuli; recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk. However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wild-type A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by downregulation of NF-kappaB activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-kappaB activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-kappaB activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-kappaB caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, Motohiro -- Sanada, Masashi -- Kato, Itaru -- Sato, Yasuharu -- Takita, Junko -- Takeuchi, Kengo -- Niwa, Akira -- Chen, Yuyan -- Nakazaki, Kumi -- Nomoto, Junko -- Asakura, Yoshitaka -- Muto, Satsuki -- Tamura, Azusa -- Iio, Mitsuru -- Akatsuka, Yoshiki -- Hayashi, Yasuhide -- Mori, Hiraku -- Igarashi, Takashi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Shigeo -- Ishikawa, Yuichi -- Okamoto, Koji -- Tobinai, Kensei -- Nakagama, Hitoshi -- Nakahata, Tatsutoshi -- Yoshino, Tadashi -- Kobayashi, Yukio -- Ogawa, Seishi -- England -- Nature. 2009 Jun 4;459(7247):712-6. doi: 10.1038/nature07969. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, Department of Pediatrics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412163" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/physiology ; Cell Line ; Cysteine Endopeptidases/*genetics/*metabolism ; DNA-Binding Proteins ; Gene Expression ; *Gene Silencing ; Genome/genetics ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/*metabolism ; Lymphoma, B-Cell/*genetics/*physiopathology ; Mice ; NF-kappa B/genetics/metabolism ; Nuclear Proteins/*genetics/*metabolism
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  • 13
    Publication Date: 2009-07-31
    Description: Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 A resolution, the location and composition of the approximately 8 A 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X(4) receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845979/" 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/PMC2845979/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzales, Eric B -- Kawate, Toshimitsu -- Gouaux, Eric -- F32 GM083615/GM/NIGMS NIH HHS/ -- F32 GM083615-01/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):599-604. doi: 10.1038/nature08218.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and 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/19641589" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Sensing Ion Channels ; Animals ; Binding Sites ; CHO Cells ; Cell Line ; Cesium/metabolism ; Chickens/*physiology ; Cricetinae ; Cricetulus ; Crystallization ; Humans ; Ions/metabolism ; *Models, Molecular ; Nerve Tissue Proteins/*chemistry ; Protein Structure, Tertiary ; Receptors, Purinergic P2/*chemistry ; Receptors, Purinergic P2X ; Sodium Channels/*chemistry ; Zebrafish/*physiology
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  • 14
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Apr 16;458(7240):807-8. doi: 10.1038/458807b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19369978" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Communicable Diseases, Emerging/epidemiology ; Community Health Services/*trends ; Delivery of Health Care/*trends ; Drug Prescriptions/economics/statistics & numerical data ; Hospitals, County/trends ; Humans ; Medical Informatics/trends ; Medical Records
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  • 15
    Publication Date: 2009-03-27
    Description: Toll-like receptors (TLRs) recognize microbial components, and evoke inflammation and immune responses. TLR stimulation activates complex gene expression networks that regulate the magnitude and duration of the immune reaction. Here we identify the TLR-inducible gene Zc3h12a as an immune response modifier that has an essential role in preventing immune disorders. Zc3h12a-deficient mice suffered from severe anaemia, and most died within 12 weeks. Zc3h12a(-/-) mice also showed augmented serum immunoglobulin levels and autoantibody production, together with a greatly increased number of plasma cells, as well as infiltration of plasma cells to the lung. Most Zc3h12a(-/-) splenic T cells showed effector/memory characteristics and produced interferon-gamma in response to T-cell receptor stimulation. Macrophages from Zc3h12a(-/-) mice showed highly increased production of interleukin (IL)-6 and IL-12p40 (also known as IL12b), but not TNF, in response to TLR ligands. Although the activation of TLR signalling pathways was normal, Il6 messenger RNA decay was severely impaired in Zc3h12a(-/-) macrophages. Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3'-untranslated region (UTR), and destabilized RNAs with 3'-UTRs for genes including Il6, Il12p40 and the calcitonin receptor gene Calcr. Zc3h12a contains a putative amino-terminal nuclease domain, and the expressed protein had RNase activity, consistent with a role in the decay of Il6 mRNA. Together, these results indicate that Zc3h12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsushita, Kazufumi -- Takeuchi, Osamu -- Standley, Daron M -- Kumagai, Yutaro -- Kawagoe, Tatsukata -- Miyake, Tohru -- Satoh, Takashi -- Kato, Hiroki -- Tsujimura, Tohru -- Nakamura, Haruki -- Akira, Shizuo -- P01 AI070167/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1185-90. doi: 10.1038/nature07924. Epub 2009 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19322177" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/metabolism ; Anemia/complications/genetics ; Animals ; Autoantibodies/blood/immunology ; Autoimmune Diseases/complications/immunology ; Cell Line ; Cytokines/biosynthesis/genetics ; Fetal Diseases/immunology ; Humans ; Immunity/*genetics/*immunology ; Inflammation Mediators/metabolism ; Interleukin-6/genetics ; Macrophages, Peritoneal/immunology/metabolism ; Mice ; Plasma Cells/cytology ; *RNA Stability ; Ribonucleases/deficiency/genetics/*metabolism ; T-Lymphocytes/immunology
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  • 16
    Publication Date: 2009-08-12
    Description: Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes, but the low frequency and tendency to induce malignant transformation compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 (also known as Pou5f1) and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735889/" 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/PMC2735889/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawamura, Teruhisa -- Suzuki, Jotaro -- Wang, Yunyuan V -- Menendez, Sergio -- Morera, Laura Batlle -- Raya, Angel -- Wahl, Geoffrey M -- Izpisua Belmonte, Juan Carlos -- 5 R01 CA061449/CA/NCI NIH HHS/ -- 5 R01 CA100845/CA/NCI NIH HHS/ -- R01 CA061449/CA/NCI NIH HHS/ -- R01 CA061449-30/CA/NCI NIH HHS/ -- R01 CA100845/CA/NCI NIH HHS/ -- R01 CA100845-05/CA/NCI NIH HHS/ -- R33 HL088293/HL/NHLBI NIH HHS/ -- R33 HL088293-03/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1140-4. doi: 10.1038/nature08311. Epub 2009 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19668186" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cellular Reprogramming/*physiology ; Cyclin-Dependent Kinase Inhibitor p21/deficiency/genetics/metabolism ; Down-Regulation ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Keratinocytes ; Male ; Mice ; Mice, Inbred C57BL ; Pluripotent Stem Cells/*cytology/*metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
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  • 17
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brumfiel, Geoff -- England -- Nature. 2009 May 28;459(7246):504-5. doi: 10.1038/459504a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478762" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Lenses ; Optical Processes ; Technology/*instrumentation
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  • 18
    Publication Date: 2009-02-27
    Description: The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from 〉2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P 〈 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148020/" 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/PMC3148020/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawashima, Yuka -- Pfafferott, Katja -- Frater, John -- Matthews, Philippa -- Payne, Rebecca -- Addo, Marylyn -- Gatanaga, Hiroyuki -- Fujiwara, Mamoru -- Hachiya, Atsuko -- Koizumi, Hirokazu -- Kuse, Nozomi -- Oka, Shinichi -- Duda, Anna -- Prendergast, Andrew -- Crawford, Hayley -- Leslie, Alasdair -- Brumme, Zabrina -- Brumme, Chanson -- Allen, Todd -- Brander, Christian -- Kaslow, Richard -- Tang, James -- Hunter, Eric -- Allen, Susan -- Mulenga, Joseph -- Branch, Songee -- Roach, Tim -- John, Mina -- Mallal, Simon -- Ogwu, Anthony -- Shapiro, Roger -- Prado, Julia G -- Fidler, Sarah -- Weber, Jonathan -- Pybus, Oliver G -- Klenerman, Paul -- Ndung'u, Thumbi -- Phillips, Rodney -- Heckerman, David -- Harrigan, P Richard -- Walker, Bruce D -- Takiguchi, Masafumi -- Goulder, Philip -- 1 R01 AI067073/AI/NIAID NIH HHS/ -- G0500384/Medical Research Council/United Kingdom -- G0501777/Medical Research Council/United Kingdom -- G108/626/Medical Research Council/United Kingdom -- R01 AI046995/AI/NIAID NIH HHS/ -- R01 AI046995-10/AI/NIAID NIH HHS/ -- R01 AI060460/AI/NIAID NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI064060-06A1/AI/NIAID NIH HHS/ -- R01AI46995/AI/NIAID NIH HHS/ -- R01AI64060/AI/NIAID NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 2;458(7238):641-5. doi: 10.1038/nature07746. Epub 2009 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242411" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Epitopes, T-Lymphocyte/chemistry/genetics/immunology ; HIV Antigens/chemistry/genetics/immunology ; HIV-1/genetics/*immunology/physiology ; HLA-B Antigens/genetics/*immunology ; Humans ; Internationality ; Leukocytes/*immunology ; Polymorphism, Genetic ; gag Gene Products, Human Immunodeficiency Virus/chemistry/genetics/immunology
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  • 19
    Publication Date: 2009-07-03
    Description: Induced pluripotent stem cells offer unprecedented potential for disease research, drug screening, toxicology and regenerative medicine. However, the process of reprogramming is inefficient and often incomplete. Here I consider reasons for bottlenecks in induced pluripotent stem cell generation, and propose a model in which most or all cells have the potential to become pluripotent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamanaka, Shinya -- England -- Nature. 2009 Jul 2;460(7251):49-52. doi: 10.1038/nature08180.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan. yamanaka@cira.kyoto-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571877" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; *Cellular Reprogramming/genetics ; Epigenesis, Genetic ; Humans ; Mice ; *Models, Biological ; Pluripotent Stem Cells/*cytology/metabolism ; Stochastic Processes ; Transduction, Genetic
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  • 20
    Publication Date: 2009-09-26
    Description: India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842210/" 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/PMC2842210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reich, David -- Thangaraj, Kumarasamy -- Patterson, Nick -- Price, Alkes L -- Singh, Lalji -- HG004168/HG/NHGRI NIH HHS/ -- R01 HG006399/HG/NHGRI NIH HHS/ -- U01 HG004168/HG/NHGRI NIH HHS/ -- U01 HG004168-03/HG/NHGRI NIH HHS/ -- England -- Nature. 2009 Sep 24;461(7263):489-94. doi: 10.1038/nature08365.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. reich@genetics.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779445" target="_blank"〉PubMed〈/a〉
    Keywords: Asia/ethnology ; Chromosomes, Human, Y/genetics ; Continental Population Groups/genetics ; DNA, Mitochondrial/genetics ; Ethnic Groups/*genetics ; Europe/ethnology ; Female ; Founder Effect ; Gene Frequency ; Genes, Recessive/genetics ; Genetic Variation/*genetics ; Genetics, Medical ; Genetics, Population ; Genome, Human/genetics ; Genomics ; Genotype ; Geography ; Humans ; India ; Language ; Linkage Disequilibrium/genetics ; Male ; Middle East/ethnology ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis
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  • 21
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Apr 9;458(7239):679. doi: 10.1038/458679a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19360033" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers/analysis ; *Early Detection of Cancer ; Humans ; Mass Screening/*standards ; Neoplasms/*diagnosis/mortality
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  • 22
    Publication Date: 2009-11-26
    Description: Mutations in the enzyme cytosolic isocitrate dehydrogenase 1 (IDH1) are a common feature of a major subset of primary human brain cancers. These mutations occur at a single amino acid residue of the IDH1 active site, resulting in loss of the enzyme's ability to catalyse conversion of isocitrate to alpha-ketoglutarate. However, only a single copy of the gene is mutated in tumours, raising the possibility that the mutations do not result in a simple loss of function. Here we show that cancer-associated IDH1 mutations result in a new ability of the enzyme to catalyse the NADPH-dependent reduction of alpha-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). Structural studies demonstrate that when arginine 132 is mutated to histidine, residues in the active site are shifted to produce structural changes consistent with reduced oxidative decarboxylation of isocitrate and acquisition of the ability to convert alpha-ketoglutarate to 2HG. Excess accumulation of 2HG has been shown to lead to an elevated risk of malignant brain tumours in patients with inborn errors of 2HG metabolism. Similarly, in human malignant gliomas harbouring IDH1 mutations, we find markedly elevated levels of 2HG. These data demonstrate that the IDH1 mutations result in production of the onco-metabolite 2HG, and indicate that the excess 2HG which accumulates in vivo contributes to the formation and malignant progression of gliomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818760/" 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/PMC2818760/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dang, Lenny -- White, David W -- Gross, Stefan -- Bennett, Bryson D -- Bittinger, Mark A -- Driggers, Edward M -- Fantin, Valeria R -- Jang, Hyun Gyung -- Jin, Shengfang -- Keenan, Marie C -- Marks, Kevin M -- Prins, Robert M -- Ward, Patrick S -- Yen, Katharine E -- Liau, Linda M -- Rabinowitz, Joshua D -- Cantley, Lewis C -- Thompson, Craig B -- Vander Heiden, Matthew G -- Su, Shinsan M -- P01 CA104838/CA/NCI NIH HHS/ -- P01 CA104838-05/CA/NCI NIH HHS/ -- P30 EB009998/EB/NIBIB NIH HHS/ -- R01 CA105463/CA/NCI NIH HHS/ -- R01 CA105463-06/CA/NCI NIH HHS/ -- R21 CA128620/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):739-44. doi: 10.1038/nature08617. Epub .〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Agios Pharmaceuticals, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19935646" target="_blank"〉PubMed〈/a〉
    Keywords: Arginine/genetics ; Brain Neoplasms/*genetics/*metabolism/pathology ; Catalytic Domain ; Cell Line ; Crystallography, X-Ray ; Disease Progression ; Enzyme Assays ; Glioma/genetics/metabolism/pathology ; Glutarates/*metabolism ; Histidine/genetics/metabolism ; Humans ; Isocitrate Dehydrogenase/*genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Models, Molecular ; Mutant Proteins/*genetics/*metabolism ; Mutation/genetics ; Protein Conformation
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  • 23
    Publication Date: 2009-12-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kayani, Saheeb Ahmed -- England -- Nature. 2009 Dec 24;462(7276):984. doi: 10.1038/462984b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033020" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; History, 20th Century ; History, 21st Century ; Humans ; Pakistan ; *Religion and Science ; Science/history
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  • 24
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maynard, Andrew -- Rejeski, David -- England -- Nature. 2009 Jul 9;460(7252):174. doi: 10.1038/460174a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Project on Emerging Nanotechnologies at the Woodrow Wilson International Center for Scholars, 1300 Pennsylvania Avenue, Washington DC 20004-3027, USA. andrew.maynard@wilsoncenter.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587746" target="_blank"〉PubMed〈/a〉
    Keywords: *Government Regulation ; Guidelines as Topic ; Humans ; Internationality ; Nanostructures/standards ; Nanotechnology/economics/*legislation & jurisprudence/*standards/statistics & ; numerical data ; *Risk Management/legislation & jurisprudence/standards ; Safety/legislation & jurisprudence/standards
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  • 25
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    Nature Publishing Group (NPG)
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reiff, Sarah B -- Striepen, Boris -- England -- Nature. 2009 Jun 18;459(7249):918-9. doi: 10.1038/459918a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536248" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Malaria, Falciparum/drug therapy/*parasitology ; Models, Biological ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/antagonists & inhibitors/*metabolism ; Vacuoles/metabolism/parasitology
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  • 26
    Publication Date: 2009-07-25
    Description: MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development, a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis. This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. In HCT116 cells and human diploid fibroblasts, p53 interacts with the Drosha processing complex through the association with DEAD-box RNA helicase p68 (also known as DDX5) and facilitates the processing of primary miRNAs to precursor miRNAs. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between Drosha complex and p68, leading to attenuation of miRNA processing activity. These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Hiroshi I -- Yamagata, Kaoru -- Sugimoto, Koichi -- Iwamoto, Takashi -- Kato, Shigeaki -- Miyazono, Kohei -- England -- Nature. 2009 Jul 23;460(7254):529-33. doi: 10.1038/nature08199.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626115" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; DNA Damage/physiology ; Gene Expression Regulation ; HCT116 Cells ; Humans ; MicroRNAs/*metabolism ; Mutation ; *RNA Processing, Post-Transcriptional ; Ribonuclease III/metabolism ; Tumor Suppressor Protein p53/genetics/*metabolism
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-21
    Description: As researchers discover more agents that alter mental states, the Chemical Weapons Convention needs modification to help ensure that the life sciences are not used for hostile purposes, says Malcolm Dando.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dando, Malcolm -- England -- Nature. 2009 Aug 20;460(7258):950-1. doi: 10.1038/460950a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Peace Studies, University of Bradford, Richmond Road, Bradford, BD7 IDP, UK. mrdando@bradford.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693065" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Warfare Agents/ethics/legislation & jurisprudence ; Central Nervous System/drug effects ; *Chemical Warfare Agents/adverse effects/standards ; Fentanyl/adverse effects ; Humans ; International Cooperation ; Military Science/*ethics/legislation & jurisprudence ; Riot Control Agents, Chemical/adverse effects
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  • 28
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    Nature Publishing Group (NPG)
    Publication Date: 2009-09-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gottlieb, Eyal -- England -- Nature. 2009 Sep 3;461(7260):44-5. doi: 10.1038/461044a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19727186" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Anoikis/physiology ; Autophagy ; Breast Neoplasms/*metabolism/*pathology ; Cell Adhesion ; Cell Survival ; Epithelial Cells/cytology/*metabolism/pathology ; Extracellular Matrix/*metabolism ; Glucose/metabolism ; Humans ; Receptor, ErbB-2/genetics/*metabolism
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2009-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swaminathan, M S -- England -- Nature. 2009 Oct 15;461(7266):894. doi: 10.1038/461894a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉M. S. Swaminathan Research Foundation, Third Cross Street, Taramani Institutional Area, Chennai 600 113, India. chairman@mssrf.res.in〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829366" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*history ; Breeding/history ; Food Supply/history ; History, 20th Century ; History, 21st Century ; Humans ; Plant Diseases/genetics/microbiology ; Triticum/genetics/physiology
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  • 30
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Apr 2;458(7238):550. doi: 10.1038/458550a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19340028" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Enteral Nutrition/ethics/utilization ; Female ; Humans ; Italy ; Living Wills/ethics/*legislation & jurisprudence ; *Patients ; *Physicians ; Right to Die/ethics/*legislation & jurisprudence ; Young Adult
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  • 31
    Publication Date: 2009-10-30
    Description: The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133736/" 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/PMC3133736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kee, Kehkooi -- Angeles, Vanessa T -- Flores, Martha -- Nguyen, Ha Nam -- Reijo Pera, Renee A -- R01 HD047721/HD/NICHD NIH HHS/ -- R01 HD047721-06/HD/NICHD NIH HHS/ -- R01HD047721/HD/NICHD NIH HHS/ -- U54 HD055764/HD/NICHD NIH HHS/ -- U54 HD055764-015755/HD/NICHD NIH HHS/ -- U54HD055764/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):222-5. doi: 10.1038/nature08562. Epub 2009 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Palo Alto, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865085" target="_blank"〉PubMed〈/a〉
    Keywords: Bone Morphogenetic Proteins/metabolism ; Cell Count ; *Cell Differentiation ; Cell Line ; Cellular Reprogramming ; Embryonic Stem Cells/cytology/metabolism ; Female ; Gene Expression ; Gene Silencing ; Genes, Reporter ; Germ Cells/*cytology/*metabolism ; *Haploidy ; Humans ; Male ; Meiosis ; Organ Specificity ; RNA-Binding Proteins/genetics/*metabolism
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  • 32
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonnell, Anna -- England -- Nature. 2009 Jun 18;459(7249):909. doi: 10.1038/459909b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536241" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fertility ; History, Ancient ; Humans ; Pregnancy ; Sculpture/*history
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  • 33
    Publication Date: 2009-07-31
    Description: P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X(4) receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in beta-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an approximately 8 A slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720809/" 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/PMC2720809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawate, Toshimitsu -- Michel, Jennifer Carlisle -- Birdsong, William T -- Gouaux, Eric -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM075026-04/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):592-8. doi: 10.1038/nature08198.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641588" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Gadolinium/metabolism ; Humans ; Ion Channels/antagonists & inhibitors/*chemistry ; Membrane Proteins/chemistry ; *Models, Molecular ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Purinergic P2 Receptor Antagonists ; Receptors, Purinergic P2/*chemistry ; Receptors, Purinergic P2X4 ; Zebrafish/*physiology ; Zebrafish Proteins/antagonists & inhibitors/*chemistry
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  • 34
    Publication Date: 2009-07-25
    Description: African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872475/" 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/PMC2872475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keele, Brandon F -- Jones, James Holland -- Terio, Karen A -- Estes, Jacob D -- Rudicell, Rebecca S -- Wilson, Michael L -- Li, Yingying -- Learn, Gerald H -- Beasley, T Mark -- Schumacher-Stankey, Joann -- Wroblewski, Emily -- Mosser, Anna -- Raphael, Jane -- Kamenya, Shadrack -- Lonsdorf, Elizabeth V -- Travis, Dominic A -- Mlengeya, Titus -- Kinsel, Michael J -- Else, James G -- Silvestri, Guido -- Goodall, Jane -- Sharp, Paul M -- Shaw, George M -- Pusey, Anne E -- Hahn, Beatrice H -- HHSN266200400088C/PHS HHS/ -- P30 AI 27767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A17134/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 AI58715/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-06A1/AI/NIAID NIH HHS/ -- RR-00165/RR/NCRR NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-059010/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 23;460(7254):515-9. doi: 10.1038/nature08200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626114" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/pathology ; Africa ; Animals ; Animals, Wild ; CD4-Positive T-Lymphocytes/immunology ; Female ; Humans ; Male ; Molecular Sequence Data ; Pan troglodytes/*virology ; Prevalence ; Simian Acquired Immunodeficiency ; Syndrome/epidemiology/immunology/*mortality/*pathology ; Simian Immunodeficiency Virus/*physiology
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  • 35
    Publication Date: 2009-02-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goudsmit, Jaap -- England -- Nature. 2009 Jan 22;457(7228):394. doi: 10.1038/457394a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jaap Goudsmit is in the Research and Development Department of Crucell Holland, PO Box 2048, Leiden, 2301 CA, the Netherlands, and in the Academic Medical Center of the University of Amsterdam. j.goudsmit@crucell.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158783" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; History, 20th Century ; History, 21st Century ; Humans ; Nobel Prize ; Prion Diseases/*history/transmission ; Prions/chemistry/*history/metabolism
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  • 36
    Publication Date: 2009-03-28
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955398/" 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/PMC3955398/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Resnik, David B -- ZIA ES102646-02/Intramural NIH HHS/ -- England -- Nature. 2009 Mar 26;458(7237):404. doi: 10.1038/458404c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325605" target="_blank"〉PubMed〈/a〉
    Keywords: Confidentiality/standards ; Human Experimentation/*standards ; Humans ; *Patient Advocacy ; Peer Review, Research/*methods/*standards ; Risk Management/methods/standards
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  • 37
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gould, Paula -- England -- Nature. 2009 Jul 16;460(7253):312-3. doi: 10.1038/460312a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19606111" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Internationality ; Molybdenum/supply & distribution ; Nuclear Fission ; Nuclear Reactors/economics/supply & distribution ; Radioisotopes/*supply & distribution ; Technetium/*supply & distribution ; Uranium
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  • 38
    Publication Date: 2009-03-10
    Description: Acetylation within the globular core domain of histone H3 on lysine 56 (H3K56) has recently been shown to have a critical role in packaging DNA into chromatin following DNA replication and repair in budding yeast. However, the function or occurrence of this specific histone mark has not been studied in multicellular eukaryotes, mainly because the Rtt109 enzyme that is known to mediate acetylation of H3K56 (H3K56ac) is fungal-specific. Here we demonstrate that the histone acetyl transferase CBP (also known as Nejire) in flies and CBP and p300 (Ep300) in humans acetylate H3K56, whereas Drosophila Sir2 and human SIRT1 and SIRT2 deacetylate H3K56ac. The histone chaperones ASF1A in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF-1 (chromatin assembly factor 1) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. We show that, in response to DNA damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumours. Our identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation and cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756583/" 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/PMC2756583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Chandrima -- Lucia, M Scott -- Hansen, Kirk C -- Tyler, Jessica K -- CA95641/CA/NCI NIH HHS/ -- GM64475/GM/NIGMS NIH HHS/ -- R01 CA095641/CA/NCI NIH HHS/ -- R01 CA095641-07/CA/NCI NIH HHS/ -- R01 GM064475/GM/NIGMS NIH HHS/ -- R01 GM064475-07/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 7;459(7243):113-7. doi: 10.1038/nature07861. Epub 2009 Mar 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19270680" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Cycle Proteins/metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Damage/physiology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*enzymology ; HeLa Cells ; Histone Deacetylases/metabolism ; Histones/*metabolism ; Humans ; Lysine/*metabolism ; Molecular Chaperones/metabolism ; Retinoblastoma-Binding Protein 4 ; Sirtuin 1 ; Sirtuin 2 ; Sirtuins/metabolism ; p300-CBP Transcription Factors/*metabolism
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  • 39
    Publication Date: 2009-07-31
    Description: Reactive oxygen species (ROS) produced by NADPH oxidase function as defence and signalling molecules related to innate immunity and various cellular responses. The activation of NADPH oxidase in response to plasma membrane receptor activation depends on the phosphorylation of cytoplasmic oxidase subunits, their translocation to membranes and the assembly of all NADPH oxidase components. Tumour necrosis factor (TNF) is a prominent stimulus of ROS production, but the molecular mechanisms by which TNF activates NADPH oxidase are poorly understood. Here we identify riboflavin kinase (RFK, formerly known as flavokinase) as a previously unrecognized TNF-receptor-1 (TNFR1)-binding protein that physically and functionally couples TNFR1 to NADPH oxidase. In mouse and human cells, RFK binds to both the TNFR1-death domain and to p22(phox), the common subunit of NADPH oxidase isoforms. RFK-mediated bridging of TNFR1 and p22(phox) is a prerequisite for TNF-induced but not for Toll-like-receptor-induced ROS production. Exogenous flavin mononucleotide or FAD was able to substitute fully for TNF stimulation of NADPH oxidase in RFK-deficient cells. RFK is rate-limiting in the synthesis of FAD, an essential prosthetic group of NADPH oxidase. The results suggest that TNF, through the activation of RFK, enhances the incorporation of FAD in NADPH oxidase enzymes, a critical step for the assembly and activation of NADPH oxidase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yazdanpanah, Benjamin -- Wiegmann, Katja -- Tchikov, Vladimir -- Krut, Oleg -- Pongratz, Carola -- Schramm, Michael -- Kleinridders, Andre -- Wunderlich, Thomas -- Kashkar, Hamid -- Utermohlen, Olaf -- Bruning, Jens C -- Schutze, Stefan -- Kronke, Martin -- England -- Nature. 2009 Aug 27;460(7259):1159-63. doi: 10.1038/nature08206. Epub 2009 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641494" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cytochrome b Group/metabolism ; Enzyme Activation ; Fibroblasts ; Flavin Mononucleotide/metabolism ; Flavin-Adenine Dinucleotide/biosynthesis/metabolism ; HeLa Cells ; Humans ; Isoenzymes/chemistry/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; NADH, NADPH Oxidoreductases/metabolism ; NADPH Oxidase/chemistry/*metabolism ; Phosphotransferases (Alcohol Group Acceptor)/deficiency/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Reactive Oxygen Species/metabolism ; Receptors, Tumor Necrosis Factor, Type I/chemistry/*metabolism
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  • 40
    Publication Date: 2009-11-03
    Description: Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H(4) receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (〈100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784146/" 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/PMC2784146/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keiser, Michael J -- Setola, Vincent -- Irwin, John J -- Laggner, Christian -- Abbas, Atheir I -- Hufeisen, Sandra J -- Jensen, Niels H -- Kuijer, Michael B -- Matos, Roberto C -- Tran, Thuy B -- Whaley, Ryan -- Glennon, Richard A -- Hert, Jerome -- Thomas, Kelan L H -- Edwards, Douglas D -- Shoichet, Brian K -- Roth, Bryan L -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 DA017204-04/DA/NIDA NIH HHS/ -- R01 DA017204-05/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH061887-09/MH/NIMH NIH HHS/ -- R01 MH061887-10/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH082441-01/MH/NIMH NIH HHS/ -- U19 MH082441-010001/MH/NIMH NIH HHS/ -- U19 MH082441-019002/MH/NIMH NIH HHS/ -- U19 MH082441-019003/MH/NIMH NIH HHS/ -- U19 MH082441-02/MH/NIMH NIH HHS/ -- U19 MH082441-020001/MH/NIMH NIH HHS/ -- U19 MH082441-029002/MH/NIMH NIH HHS/ -- U19 MH082441-03/MH/NIMH NIH HHS/ -- U19 MH082441-030001/MH/NIMH NIH HHS/ -- U19 MH082441-039002/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):175-81. doi: 10.1038/nature08506. Epub 2009 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, California 94143-2550, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19881490" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computational Biology ; Databases, Factual ; Drug Evaluation, Preclinical/*methods ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Ligands ; Mice ; Mice, Knockout ; Off-Label Use ; Pharmaceutical Preparations/*metabolism ; Receptors, Serotonin/metabolism ; *Substrate Specificity ; United States ; United States Food and Drug Administration
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  • 41
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Mar 26;458(7237):385. doi: 10.1038/458385a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325580" target="_blank"〉PubMed〈/a〉
    Keywords: Embryo Research/*ethics/*legislation & jurisprudence ; *Embryonic Stem Cells ; Federal Government ; Great Britain ; Humans ; *Public Opinion ; *Research Personnel ; United States
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  • 42
    Publication Date: 2009-08-21
    Description: A decision is a commitment to a proposition or plan of action based on evidence and the expected costs and benefits associated with the outcome. Progress in a variety of fields has led to a quantitative understanding of the mechanisms that evaluate evidence and reach a decision. Several formalisms propose that a representation of noisy evidence is evaluated against a criterion to produce a decision. Without additional evidence, however, these formalisms fail to explain why a decision-maker would change their mind. Here we extend a model, developed to account for both the timing and the accuracy of the initial decision, to explain subsequent changes of mind. Subjects made decisions about a noisy visual stimulus, which they indicated by moving a handle. Although they received no additional information after initiating their movement, their hand trajectories betrayed a change of mind in some trials. We propose that noisy evidence is accumulated over time until it reaches a criterion level, or bound, which determines the initial decision, and that the brain exploits information that is in the processing pipeline when the initial decision is made to subsequently either reverse or reaffirm the initial decision. The model explains both the frequency of changes of mind as well as their dependence on both task difficulty and whether the initial decision was accurate or erroneous. The theoretical and experimental findings advance the understanding of decision-making to the highly flexible and cognitive acts of vacillation and self-correction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875179/" 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/PMC2875179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Resulaj, Arbora -- Kiani, Roozbeh -- Wolpert, Daniel M -- Shadlen, Michael N -- 077730/Wellcome Trust/United Kingdom -- EY11378/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Sep 10;461(7261):263-6. doi: 10.1038/nature08275. Epub 2009 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational and Biological Learning Laboratory, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693010" target="_blank"〉PubMed〈/a〉
    Keywords: Computers ; Cues ; Decision Making/*physiology ; Female ; Hand/physiology ; Humans ; Male ; Models, Neurological ; Models, Psychological ; Motion ; Movement ; Photic Stimulation ; Psychomotor Performance ; Reaction Time ; Time Factors
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  • 43
    Publication Date: 2009-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meek, Thomas H -- Meek, Laura A -- England -- Nature. 2009 May 7;459(7243):31. doi: 10.1038/459031b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19424137" target="_blank"〉PubMed〈/a〉
    Keywords: *Economics/trends ; Humans ; Poverty ; Socioeconomic Factors ; *Water Supply
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  • 44
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowans, James -- England -- Nature. 2009 May 28;459(7246):506. doi: 10.1038/459506c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478763" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/history ; Correspondence as Topic/history ; Female ; Great Britain ; History, 20th Century ; Humans ; Periodicals as Topic/*history
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  • 45
    Publication Date: 2009-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kell, Douglas -- England -- Nature. 2009 Aug 6;460(7256):669. doi: 10.1038/460669e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Manchester, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661875" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Chemistry ; Creutzfeldt-Jakob Syndrome/metabolism ; Ferritins/metabolism ; Humans ; Hydroxyl Radical/metabolism ; Iron/chemistry/*metabolism ; PrPSc Proteins/*metabolism ; Prion Diseases/*metabolism ; Scrapie/metabolism ; Systems Biology
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  • 46
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Mar 26;458(7237):385. doi: 10.1038/458386a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19325578" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; *Genes ; *Genetic Testing/economics/legislation & jurisprudence ; History, 20th Century ; History, 21st Century ; Humans ; Patents as Topic/history/*legislation & jurisprudence/*statistics & numerical ; data ; United States
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  • 47
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    Nature Publishing Group (NPG)
    Publication Date: 2009-12-04
    Description: The ability to produce stem cells by induced pluripotency (iPS reprogramming) has rekindled an interest in earlier studies showing that transcription factors can directly convert specialized cells from one lineage to another. Lineage reprogramming has become a powerful tool to study cell fate choice during differentiation, akin to inducing mutations for the discovery of gene functions. The lessons learnt provide a rubric for how cells may be manipulated for therapeutic purposes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graf, Thomas -- Enver, Tariq -- MC_U137973817/Medical Research Council/United Kingdom -- England -- Nature. 2009 Dec 3;462(7273):587-94. doi: 10.1038/nature08533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genomic Regulation and ICREA, 08003 Barcelona, Spain. thomas.graf@crg.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956253" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage/*physiology ; Cellular Reprogramming/*genetics ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks/physiology ; Humans ; Pluripotent Stem Cells/cytology/*metabolism ; Transcription Factors/*metabolism
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  • 48
    Publication Date: 2009-06-16
    Description: Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712122/" 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/PMC2712122/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Atsunobu -- Baffi, Judit Z -- Kleinman, Mark E -- Cho, Won Gil -- Nozaki, Miho -- Yamada, Kiyoshi -- Kaneko, Hiroki -- Albuquerque, Romulo J C -- Dridi, Sami -- Saito, Kuniharu -- Raisler, Brian J -- Budd, Steven J -- Geisen, Pete -- Munitz, Ariel -- Ambati, Balamurali K -- Green, Martha G -- Ishibashi, Tatsuro -- Wright, John D -- Humbles, Alison A -- Gerard, Craig J -- Ogura, Yuichiro -- Pan, Yuzhen -- Smith, Justine R -- Grisanti, Salvatore -- Hartnett, M Elizabeth -- Rothenberg, Marc E -- Ambati, Jayakrishna -- AI039759/AI/NIAID NIH HHS/ -- AI45898/AI/NIAID NIH HHS/ -- DK076893/DK/NIDDK NIH HHS/ -- EY010572/EY/NEI NIH HHS/ -- EY015130/EY/NEI NIH HHS/ -- EY015422/EY/NEI NIH HHS/ -- EY017011/EY/NEI NIH HHS/ -- EY017182/EY/NEI NIH HHS/ -- EY017950/EY/NEI NIH HHS/ -- EY018350/EY/NEI NIH HHS/ -- EY018836/EY/NEI NIH HHS/ -- R01 DK076893/DK/NIDDK NIH HHS/ -- R01 EY015422/EY/NEI NIH HHS/ -- R01 EY015422-04/EY/NEI NIH HHS/ -- R01 EY018350/EY/NEI NIH HHS/ -- R01 EY018350-02/EY/NEI NIH HHS/ -- R01 EY018836/EY/NEI NIH HHS/ -- R01 EY018836-02/EY/NEI NIH HHS/ -- England -- Nature. 2009 Jul 9;460(7252):225-30. doi: 10.1038/nature08151. Epub 2009 Jun 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology & Visual Science, University of Kentucky, Lexington, Kentucky 40506, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19525930" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chemokine CCL11/antagonists & inhibitors/metabolism ; Chemokine CCL24/antagonists & inhibitors/metabolism ; Chemokines, CC/antagonists & inhibitors/metabolism ; Choroid/blood supply/cytology/metabolism ; Choroidal Neovascularization/diagnosis/metabolism ; Disease Models, Animal ; Endothelial Cells/cytology/metabolism ; Humans ; Inflammation ; Leukocytes ; Ligands ; Macular Degeneration/*diagnosis/metabolism/*therapy ; Mice ; Mice, Inbred C57BL ; Quantum Dots ; Receptors, CCR3/analysis/*antagonists & ; inhibitors/genetics/immunology/*metabolism ; Retina/drug effects/pathology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/immunology
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  • 49
    Publication Date: 2009-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meisenberg, Gerhard -- England -- Nature. 2009 Mar 12;458(7235):145. doi: 10.1038/458145a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279609" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/*genetics ; Genetic Research/ethics ; *Genetics, Medical/ethics/standards ; Genetics, Population/ethics ; Humans ; Intelligence/*genetics ; *Social Justice/ethics/standards
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  • 50
    Publication Date: 2009-02-20
    Description: Nuclear magnetic resonance (NMR) is one of the most versatile experimental methods in chemistry, physics and biology, providing insight into the structure and dynamics of matter at the molecular scale. Its imaging variant-magnetic resonance imaging (MRI)-is widely used to examine the anatomy, physiology and metabolism of the human body. NMR signal detection is traditionally based on Faraday induction in one or multiple radio-frequency resonators that are brought into close proximity with the sample. Alternative principles involving structured-material flux guides, superconducting quantum interference devices, atomic magnetometers, Hall probes or magnetoresistive elements have been explored. However, a common feature of all NMR implementations until now is that they rely on close coupling between the detector and the object under investigation. Here we show that NMR can also be excited and detected by long-range interaction, relying on travelling radio-frequency waves sent and received by an antenna. One benefit of this approach is more uniform coverage of samples that are larger than the wavelength of the NMR signal-an important current issue in MRI of humans at very high magnetic fields. By allowing a significant distance between the probe and the sample, travelling-wave interaction also introduces new possibilities in the design of NMR experiments and systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunner, David O -- De Zanche, Nicola -- Frohlich, Jurg -- Paska, Jan -- Pruessmann, Klaas P -- England -- Nature. 2009 Feb 19;457(7232):994-8. doi: 10.1038/nature07752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225521" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Magnetic Resonance Spectroscopy/instrumentation/*methods ; Phantoms, Imaging
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  • 51
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-04-11
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822621/" 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/PMC2822621/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunet, Anne -- R01 AG031198/AG/NIA NIH HHS/ -- R01 AG031198-01A1/AG/NIA NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):713-4. doi: 10.1038/458713a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19360073" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/physiology ; *Caloric Restriction ; Humans ; Insulin/physiology ; Neoplasms/*diet therapy ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction/physiology ; Tumor Cells, Cultured
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  • 52
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Mar 19;458(7236):259-60. doi: 10.1038/458259b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295554" target="_blank"〉PubMed〈/a〉
    Keywords: Confidentiality/ethics/legislation & jurisprudence/standards/trends ; Federal Government ; Humans ; Medical Informatics/*economics/ethics/standards/*trends ; *Medical Records/economics ; United States
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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellars, Paul -- England -- Nature. 2009 May 14;459(7244):176-7. doi: 10.1038/459176a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444200" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Archaeology ; Female ; Germany ; History, Ancient ; Horns/chemistry ; Humans ; Sculpture/*history ; Sex Characteristics ; Symbolism
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  • 54
    Publication Date: 2009-07-03
    Description: The generation and expansion of diverse cardiovascular cell lineages is a critical step during human cardiogenesis, with major implications for congenital heart disease. Unravelling the mechanisms for the diversification of human heart cell lineages has been hampered by the lack of genetic tools to purify early cardiac progenitors and define their developmental potential. Recent studies in the mouse embryo have identified a multipotent cardiac progenitor that contributes to all of the major cell types in the murine heart. In contrast to murine development, human cardiogenesis has a much longer onset of heart cell lineage diversification and expansion, suggesting divergent pathways. Here we identify a diverse set of human fetal ISL1(+) cardiovascular progenitors that give rise to the cardiomyocyte, smooth muscle and endothelial cell lineages. Using two independent transgenic and gene-targeting approaches in human embryonic stem cell lines, we show that purified ISL1(+) primordial progenitors are capable of self-renewal and expansion before differentiation into the three major cell types in the heart. These results lay the foundation for the generation of human model systems for cardiovascular disease and novel approaches for human regenerative cardiovascular medicine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bu, Lei -- Jiang, Xin -- Martin-Puig, Silvia -- Caron, Leslie -- Zhu, Shenjun -- Shao, Ying -- Roberts, Drucilla J -- Huang, Paul L -- Domian, Ibrahim J -- Chien, Kenneth R -- England -- Nature. 2009 Jul 2;460(7251):113-7. doi: 10.1038/nature08191.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3208, 185 Cambridge Street, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571884" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation ; Cell Division ; Cell Line ; *Cell Lineage ; Coculture Techniques ; Embryonic Stem Cells/cytology/metabolism ; Endothelial Cells/cytology ; Fetus/cytology/embryology ; Heart/embryology ; Homeodomain Proteins/*metabolism ; Humans ; LIM-Homeodomain Proteins ; Multipotent Stem Cells/*cytology/*metabolism ; Muscle, Smooth/cytology ; Myocardium/*cytology ; Myocytes, Cardiac/cytology ; Transcription Factors ; Wnt Proteins/metabolism ; Wnt3 Protein
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  • 55
    Publication Date: 2009-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tammaro, Paolo -- England -- Nature. 2009 Mar 5;458(7234):11. doi: 10.1038/458011e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Manchester, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262629" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Arabidopsis/cytology/genetics/metabolism ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Chloride Channels/*chemistry/genetics/*metabolism ; Chlorides/*metabolism ; Humans ; Ion Transport ; Nitrates/*metabolism
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  • 56
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grant, Maria -- England -- Nature. 2009 Jul 9;460(7252):182-3. doi: 10.1038/460182a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587753" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemokine CCL11/antagonists & inhibitors/metabolism ; Chemokine CCL24/antagonists & inhibitors/metabolism ; Chemokines, CC/antagonists & inhibitors/metabolism ; Choroid/blood supply/cytology/metabolism ; Choroidal Neovascularization/diagnosis/metabolism ; Humans ; Hypersensitivity/metabolism ; Inflammation ; Macular Degeneration/diagnosis/*metabolism/therapy ; Mice ; Receptors, CCR3/antagonists & inhibitors/immunology/*metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Mar 12;458(7235):240-1. doi: 10.1038/458240a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279642" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Human/genetics ; DNA, Intergenic/genetics/*metabolism ; Gene Expression Profiling/methods/*trends ; Humans ; RNA/genetics/*metabolism
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchanan, Mark -- England -- Nature. 2009 Jan 29;457(7229):528-30. doi: 10.1038/457528a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177103" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Nonverbal Communication/*physiology/psychology ; *Social Behavior ; Social Sciences/*instrumentation/*methods/trends
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  • 59
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Alice M -- Colpaert, Francis C -- England -- Nature. 2009 Jan 29;457(7229):533. doi: 10.1038/457533a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177109" target="_blank"〉PubMed〈/a〉
    Keywords: Amphetamines/*administration & dosage/adverse effects/*pharmacology ; Animals ; *Biomedical Enhancement ; Cognition/*drug effects/physiology ; *Health ; Humans ; Mental Recall/*drug effects/*physiology
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  • 60
    Publication Date: 2009-11-20
    Description: The release of fossil fuel CO(2) to the atmosphere by human activity has been implicated as the predominant cause of recent global climate change. The ocean plays a crucial role in mitigating the effects of this perturbation to the climate system, sequestering 20 to 35 per cent of anthropogenic CO(2) emissions. Although much progress has been made in recent years in understanding and quantifying this sink, considerable uncertainties remain as to the distribution of anthropogenic CO(2) in the ocean, its rate of uptake over the industrial era, and the relative roles of the ocean and terrestrial biosphere in anthropogenic CO(2) sequestration. Here we address these questions by presenting an observationally based reconstruction of the spatially resolved, time-dependent history of anthropogenic carbon in the ocean over the industrial era. Our approach is based on the recognition that the transport of tracers in the ocean can be described by a Green's function, which we estimate from tracer data using a maximum entropy deconvolution technique. Our results indicate that ocean uptake of anthropogenic CO(2) has increased sharply since the 1950s, with a small decline in the rate of increase in the last few decades. We estimate the inventory and uptake rate of anthropogenic CO(2) in 2008 at 140 +/- 25 Pg C and 2.3 +/- 0.6 Pg C yr(-1), respectively. We find that the Southern Ocean is the primary conduit by which this CO(2) enters the ocean (contributing over 40 per cent of the anthropogenic CO(2) inventory in the ocean in 2008). Our results also suggest that the terrestrial biosphere was a source of CO(2) until the 1940s, subsequently turning into a sink. Taken over the entire industrial period, and accounting for uncertainties, we estimate that the terrestrial biosphere has been anywhere from neutral to a net source of CO(2), contributing up to half as much CO(2) as has been taken up by the ocean over the same period.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khatiwala, S -- Primeau, F -- Hall, T -- England -- Nature. 2009 Nov 19;462(7271):346-9. doi: 10.1038/nature08526.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lamont-Doherty Earth Observatory of Columbia University, Palisades, New York 10964, USA. spk@ldeo.columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924213" target="_blank"〉PubMed〈/a〉
    Keywords: Carbon Dioxide/*analysis/metabolism ; Humans ; Models, Theoretical ; Oceans and Seas ; Seawater/*chemistry ; Time Factors
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  • 61
    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graves, Jennifer A Marshall -- England -- Nature. 2009 Sep 10;461(7261):177-8. doi: 10.1038/461177a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chick Embryo ; Chickens/*genetics/*physiology ; Disorders of Sex Development ; Evolution, Molecular ; Female ; Gene Dosage/genetics ; Humans ; Male ; Models, Genetic ; Ovary/embryology/metabolism ; RNA Interference ; SOX9 Transcription Factor/genetics/metabolism ; Sex Chromosomes/*genetics ; *Sex Determination Processes ; Testis/embryology/metabolism ; Transcription Factors/deficiency/*genetics/*metabolism
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  • 62
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Larry J -- England -- Nature. 2009 Jan 8;457(7226):148. doi: 10.1038/457148a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA. lyoun03@emory.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19129828" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/genetics/physiology ; Dopamine/metabolism ; Female ; Humans ; *Love ; Male ; Maternal Behavior/physiology ; Oxytocin/*metabolism ; Pair Bond ; Paternal Behavior ; Receptors, Vasopressin/genetics/metabolism ; Sexual Behavior/drug effects/physiology ; Vasopressins/*metabolism
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  • 63
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    Nature Publishing Group (NPG)
    Publication Date: 2009-12-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2009 Dec 24;462(7276):962-3. doi: 10.1038/462962a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20033008" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change ; Economic Recession ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology ; Moon ; *Research/economics/legislation & jurisprudence
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Mar 12;458(7235):125. doi: 10.1038/458125a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279578" target="_blank"〉PubMed〈/a〉
    Keywords: Embryo Research/economics/legislation & jurisprudence ; *Embryonic Stem Cells ; Ethics, Research ; Humans ; *Policy Making ; Public Opinion
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  • 65
    Publication Date: 2009-09-29
    Description: Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signalling cascades. Here we show that human JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates Tyr 41 (Y41) on histone H3. Heterochromatin protein 1alpha (HP1alpha), but not HP1beta, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukaemic cells decreases both the expression of the haematopoietic oncogene lmo2 and the phosphorylation of H3Y41 at its promoter, while simultaneously increasing the binding of HP1alpha at the same site. Tauhese results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, jak2 and lmo2, involved in normal haematopoiesis and leukaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785147/" 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/PMC3785147/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, Mark A -- Bannister, Andrew J -- Gottgens, Berthold -- Foster, Samuel D -- Bartke, Till -- Green, Anthony R -- Kouzarides, Tony -- 089957/Wellcome Trust/United Kingdom -- 12765/Cancer Research UK/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- MC_UP_1102/2/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Oct 8;461(7265):819-22. doi: 10.1038/nature08448. Epub 2009 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19783980" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Binding Sites ; Cell Line ; Cell Nucleus/enzymology ; Chromatin/chemistry/*metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/cytology/enzymology ; Histones/chemistry/genetics/*metabolism ; Humans ; Janus Kinase 2/antagonists & inhibitors/*metabolism ; LIM Domain Proteins ; Leukemia/enzymology/genetics/metabolism/pathology ; Metalloproteins/genetics ; Mice ; Oncogenes/genetics ; Phosphorylation ; Promoter Regions, Genetic/genetics ; Protein Binding ; Proto-Oncogene Proteins ; Signal Transduction ; Tyrosine/metabolism
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  • 66
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    Publication Date: 2009-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daw, Rosamund -- Tonzani, Stefano -- England -- Nature. 2009 Nov 26;462(7272):425. doi: 10.1038/462425a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940911" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biocompatible Materials/chemistry/metabolism/therapeutic use ; *Biomedical Research/trends ; Humans
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  • 67
    Publication Date: 2009-04-24
    Description: Mammals rely heavily on olfaction to interact adequately with each other and with their environment. They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant, trace amine-associated receptor and vomeronasal type 1 (ref. 4) or 2 (refs 5-7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riviere, Stephane -- Challet, Ludivine -- Fluegge, Daniela -- Spehr, Marc -- Rodriguez, Ivan -- England -- Nature. 2009 May 28;459(7246):574-7. doi: 10.1038/nature08029.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology and Animal Biology, and National Center of Competence Frontiers in Genetics, University of Geneva, 1205 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19387439" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium Signaling ; Cell Line ; Dendrites/drug effects/metabolism ; *Disease ; Gene Expression Profiling ; Humans ; Inflammation/pathology ; Ligands ; Mice ; Olfactory Perception/drug effects/*physiology ; Olfactory Receptor Neurons/cytology/drug effects/*metabolism ; Organ Specificity ; Receptors, Formyl Peptide/genetics/*metabolism ; Smell/drug effects/*physiology ; Vomeronasal Organ/*cytology/drug effects/physiology
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  • 68
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    Publication Date: 2009-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2009 Dec 3;462(7273):562-4. doi: 10.1038/462562a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956235" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior/physiology ; *Behavior, Animal ; Behavioral Research/*instrumentation/methods ; Drosophila melanogaster/*physiology ; Female ; Humans ; Male ; Software ; Video Recording/instrumentation/methods
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  • 69
    Publication Date: 2009-09-01
    Description: Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jeong Beom -- Greber, Boris -- Arauzo-Bravo, Marcos J -- Meyer, Johann -- Park, Kook In -- Zaehres, Holm -- Scholer, Hans R -- England -- Nature. 2009 Oct 1;461(7264):649-3. doi: 10.1038/nature08436.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Rontgenstrasse 20, 48149 Munster, NRW, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19718018" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers/analysis ; *Cell Dedifferentiation ; Cell Differentiation ; Cell Line ; *Cellular Reprogramming ; DNA Methylation ; Embryonic Stem Cells/cytology/metabolism ; Epigenesis, Genetic ; Fetus/*cytology ; Gene Expression Profiling ; Germ Layers/cytology/metabolism ; Humans ; Mice ; Neurons/*cytology/metabolism ; Octamer Transcription Factor-3/genetics/*metabolism ; Pluripotent Stem Cells/*cytology/*metabolism
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  • 70
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2009 Nov 26;462(7272):403. doi: 10.1038/462403a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940891" target="_blank"〉PubMed〈/a〉
    Keywords: Brain/*anatomy & histology/pathology/*physiology/physiopathology ; Brain Mapping/methods/trends ; Humans ; Male ; Memory/physiology ; Models, Neurological ; Molecular Imaging/methods/trends ; Neuroanatomy/*methods/trends
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  • 71
    Publication Date: 2009-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rockenbach, Bettina -- Milinski, Manfred -- England -- Nature. 2009 Jan 1;457(7225):39-40. doi: 10.1038/457039a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122632" target="_blank"〉PubMed〈/a〉
    Keywords: Altruism ; Biological Evolution ; *Cooperative Behavior ; Cost-Benefit Analysis ; Female ; *Game Theory ; Humans ; Male ; Models, Psychological ; *Punishment/psychology
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  • 72
    Publication Date: 2009-05-02
    Description: The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814168/" 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/PMC2814168/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Douglas R -- Kroemer, Guido -- P01 CA069381/CA/NCI NIH HHS/ -- P01 CA069381-140010/CA/NCI NIH HHS/ -- R01 AI040646/AI/NIAID NIH HHS/ -- R01 AI040646-14/AI/NIAID NIH HHS/ -- R01 AI044828/AI/NIAID NIH HHS/ -- R01 AI044828-12/AI/NIAID NIH HHS/ -- R01 AI047891/AI/NIAID NIH HHS/ -- R01 AI047891-11/AI/NIAID NIH HHS/ -- R37 GM052735/GM/NIGMS NIH HHS/ -- R37 GM052735-19/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1127-30. doi: 10.1038/nature07986.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. douglas.green@stjude.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407794" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Autophagy ; Cell Nucleus/metabolism ; Cytoplasm/*metabolism ; Humans ; Mitochondria/metabolism ; Neoplasms/metabolism/pathology ; Transcription, Genetic ; Tumor Suppressor Protein p53/genetics/*metabolism
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  • 73
    Publication Date: 2009-07-10
    Description: Recent advances in sequencing technologies have initiated an era of personal genome sequences. To date, human genome sequences have been reported for individuals with ancestry in three distinct geographical regions: a Yoruba African, two individuals of northwest European origin, and a person from China. Here we provide a highly annotated, whole-genome sequence for a Korean individual, known as AK1. The genome of AK1 was determined by an exacting, combined approach that included whole-genome shotgun sequencing (27.8x coverage), targeted bacterial artificial chromosome sequencing, and high-resolution comparative genomic hybridization using custom microarrays featuring more than 24 million probes. Alignment to the NCBI reference, a composite of several ethnic clades, disclosed nearly 3.45 million single nucleotide polymorphisms (SNPs), including 10,162 non-synonymous SNPs, and 170,202 deletion or insertion polymorphisms (indels). SNP and indel densities were strongly correlated genome-wide. Applying very conservative criteria yielded highly reliable copy number variants for clinical considerations. Potential medical phenotypes were annotated for non-synonymous SNPs, coding domain indels, and structural variants. The integration of several human whole-genome sequences derived from several ethnic groups will assist in understanding genetic ancestry, migration patterns and population bottlenecks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860965/" 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/PMC2860965/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jong-Il -- Ju, Young Seok -- Park, Hansoo -- Kim, Sheehyun -- Lee, Seonwook -- Yi, Jae-Hyuk -- Mudge, Joann -- Miller, Neil A -- Hong, Dongwan -- Bell, Callum J -- Kim, Hye-Sun -- Chung, In-Soon -- Lee, Woo-Chung -- Lee, Ji-Sun -- Seo, Seung-Hyun -- Yun, Ji-Young -- Woo, Hyun Nyun -- Lee, Heewook -- Suh, Dongwhan -- Lee, Seungbok -- Kim, Hyun-Jin -- Yavartanoo, Maryam -- Kwak, Minhye -- Zheng, Ying -- Lee, Mi Kyeong -- Park, Hyunjun -- Kim, Jeong Yeon -- Gokcumen, Omer -- Mills, Ryan E -- Zaranek, Alexander Wait -- Thakuria, Joseph -- Wu, Xiaodi -- Kim, Ryan W -- Huntley, Jim J -- Luo, Shujun -- Schroth, Gary P -- Wu, Thomas D -- Kim, HyeRan -- Yang, Kap-Seok -- Park, Woong-Yang -- Kim, Hyungtae -- Church, George M -- Lee, Charles -- Kingsmore, Stephen F -- Seo, Jeong-Sun -- HG004221/HG/NHGRI NIH HHS/ -- P20 RR016480/RR/NCRR NIH HHS/ -- P20 RR016480-08/RR/NCRR NIH HHS/ -- RR016480/RR/NCRR NIH HHS/ -- U01 AI066569/AI/NIAID NIH HHS/ -- U01 AI066569-04/AI/NIAID NIH HHS/ -- U19 HD077693/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1011-5. doi: 10.1038/nature08211. Epub 2009 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587683" target="_blank"〉PubMed〈/a〉
    Keywords: Asian Continental Ancestry Group/*genetics ; Chromosomes, Artificial, Bacterial/genetics ; Comparative Genomic Hybridization ; Computational Biology ; Genome, Human/*genetics ; Humans ; INDEL Mutation/genetics ; Korea ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis, DNA
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  • 74
    Publication Date: 2009-10-23
    Description: NF-kappaB transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival. They have also been implicated in cellular transformation and tumorigenesis. However, despite extensive biochemical characterization of NF-kappaB signalling during the past twenty years, the requirement for NF-kappaB in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-kappaB pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-kappaB activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-kappaB inhibition. Furthermore, the inhibition of NF-kappaB signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-kappaB signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-kappaB inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780341/" 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/PMC2780341/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meylan, Etienne -- Dooley, Alison L -- Feldser, David M -- Shen, Lynn -- Turk, Erin -- Ouyang, Chensi -- Jacks, Tyler -- P30 CA014051/CA/NCI NIH HHS/ -- P30 CA014051-37/CA/NCI NIH HHS/ -- P30 CA014051-38/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Nov 5;462(7269):104-7. doi: 10.1038/nature08462. Epub 2009 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Koch Institute for Integrative Cancer Research, and Department of Biology, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847165" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/*metabolism/*pathology ; Animals ; Apoptosis ; Carcinoma, Non-Small-Cell Lung/metabolism/pathology ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Cells, Cultured ; DNA/metabolism ; *Disease Models, Animal ; Fibroblasts ; Genes, p53/genetics ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Mice ; NF-kappa B/antagonists & inhibitors/*metabolism ; Oncogene Protein p21(ras)/genetics/metabolism ; *Signal Transduction ; Transcription Factor RelA/metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/metabolism
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  • 75
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregory, Christopher -- England -- Nature. 2009 Sep 10;461(7261):181-2. doi: 10.1038/461181a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741694" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism/secretion ; Animals ; Apoptosis/*physiology ; Chemotactic Factors/metabolism/secretion ; Chemotaxis/drug effects ; Culture Media, Conditioned/metabolism/pharmacology ; Humans ; Macrophages/cytology/drug effects/metabolism ; Mice ; Monocytes/cytology/drug effects/metabolism ; Phagocytes/*cytology/drug effects/metabolism ; Phagocytosis/drug effects/*physiology ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2Y2 ; *Signal Transduction/drug effects ; Thymus Gland/*cytology ; Uridine Triphosphate/*metabolism/secretion
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  • 76
    Publication Date: 2009-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Michalakis, Yannis -- Renaud, Francois -- England -- Nature. 2009 Nov 19;462(7271):298-300. doi: 10.1038/462298a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924207" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Culicidae/microbiology/parasitology/*physiology ; Fungi/physiology ; Humans ; Insect Control ; Insect Vectors/microbiology/*physiology ; Insecticides ; *Malaria/parasitology/physiopathology/prevention & control/transmission ; Mutation ; Plasmodium/genetics/*physiology
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  • 77
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-09-15
    Description: Can Philadelphia's biotechnology industry absorb the jobs lost from pharmaceutical companies? Kerry Grens investigates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grens, Kerry -- England -- Nature. 2009 Sep 10;461(7261):300-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19750593" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/*economics/*manpower ; Drug Industry/*economics/*manpower/organization & administration ; Employment/statistics & numerical data ; Humans ; Investments ; Philadelphia ; Unemployment/statistics & numerical data
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  • 78
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millar, Sarah E -- England -- Nature. 2009 Jul 2;460(7251):44-5. doi: 10.1038/460044a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Choristoma/genetics/metabolism/pathology ; Chromatin/genetics ; DNA Helicases/metabolism ; Humans ; Nuclear Proteins/metabolism ; *Signal Transduction ; Telomerase/*metabolism ; Transcription Factors/metabolism ; Wnt Proteins/genetics/*metabolism ; Xenopus laevis/embryology/metabolism ; beta Catenin/deficiency/genetics/*metabolism
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  • 79
    Publication Date: 2009-04-10
    Description: The repair of DNA double-strand breaks (DSBs) is tightly regulated during the cell cycle. In G1 phase, the absence of a sister chromatid means that repair of DSBs occurs through non-homologous end-joining or microhomology-mediated end-joining (MMEJ). These pathways often involve loss of DNA sequences at the break site and are therefore error-prone. In late S and G2 phases, even though DNA end-joining pathways remain functional, there is an increase in repair of DSBs by homologous recombination, which is mostly error-free. Consequently, the relative contribution of these different pathways to DSB repair in the cell cycle has a large influence on the maintenance of genetic integrity. It has remained unknown how DSBs are directed for repair by different, potentially competing, repair pathways. Here we identify a role for CtIP (also known as RBBP8) in this process in the avian B-cell line DT40. We establish that CtIP is required not only for repair of DSBs by homologous recombination in S/G2 phase but also for MMEJ in G1. The function of CtIP in homologous recombination, but not MMEJ, is dependent on the phosphorylation of serine residue 327 and recruitment of BRCA1. Cells expressing CtIP protein that cannot be phosphorylated at serine 327 are specifically defective in homologous recombination and have a decreased level of single-stranded DNA after DNA damage, whereas MMEJ remains unaffected. Our data support a model in which phosphorylation of serine 327 of CtIP as cells enter S phase and the recruitment of BRCA1 functions as a molecular switch to shift the balance of DSB repair from error-prone DNA end-joining to error-free homologous recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857324/" 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/PMC2857324/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Maximina H -- Hiom, Kevin -- MC_U105184300/Medical Research Council/United Kingdom -- U.1051.03.005(78826)/Medical Research Council/United Kingdom -- England -- Nature. 2009 May 21;459(7245):460-3. doi: 10.1038/nature07955. Epub 2009 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19357644" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avian Proteins/*metabolism ; B-Lymphocytes/cytology/metabolism ; BRCA1 Protein/*metabolism ; Carrier Proteins/genetics/*metabolism ; *Cell Cycle ; Cell Line ; Chickens ; Cisplatin/pharmacology ; *DNA Breaks, Double-Stranded/radiation effects ; DNA Repair/genetics/*physiology ; G1 Phase ; G2 Phase ; Humans ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Recombination, Genetic/genetics ; S Phase ; X-Rays
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  • 80
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchenau, Jurgen -- England -- Nature. 2009 Nov 19;462(7271):284-5. doi: 10.1038/462284a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of History at the University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, North Carolina 28223, USA. jbuchenau@uncc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924194" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; Emigration and Immigration ; Europe ; History, 19th Century ; History, 20th Century ; Humans ; Latin America ; Public Policy/history/*trends
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  • 81
    Publication Date: 2009-04-17
    Description: Interaction specificity is a required feature of biological networks and a necessary characteristic of protein or small-molecule reagents and therapeutics. The ability to alter or inhibit protein interactions selectively would advance basic and applied molecular science. Assessing or modelling interaction specificity requires treating multiple competing complexes, which presents computational and experimental challenges. Here we present a computational framework for designing protein-interaction specificity and use it to identify specific peptide partners for human basic-region leucine zipper (bZIP) transcription factors. Protein microarrays were used to characterize designed, synthetic ligands for all but one of 20 bZIP families. The bZIP proteins share strong sequence and structural similarities and thus are challenging targets to bind specifically. Nevertheless, many of the designs, including examples that bind the oncoproteins c-Jun, c-Fos and c-Maf (also called JUN, FOS and MAF, respectively), were selective for their targets over all 19 other families. Collectively, the designs exhibit a wide range of interaction profiles and demonstrate that human bZIPs have only sparsely sampled the possible interaction space accessible to them. Our computational method provides a way to systematically analyse trade-offs between stability and specificity and is suitable for use with many types of structure-scoring functions; thus, it may prove broadly useful as a tool for protein design.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748673/" 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/PMC2748673/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grigoryan, Gevorg -- Reinke, Aaron W -- Keating, Amy E -- GM67681/GM/NIGMS NIH HHS/ -- R01 GM067681/GM/NIGMS NIH HHS/ -- R01 GM067681-04/GM/NIGMS NIH HHS/ -- R01 GM067681-05/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 16;458(7240):859-64. doi: 10.1038/nature07885.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MIT Department of Biology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19370028" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Basic-Leucine Zipper Transcription Factors/*chemistry/classification/*metabolism ; Computational Biology/*methods ; Drug Design ; Humans ; Leucine Zippers ; Protein Array Analysis ; Protein Binding ; Protein Engineering/*methods ; Reproducibility of Results ; Substrate Specificity
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  • 82
    Publication Date: 2009-05-05
    Description: The proteasome is a protease that controls diverse processes in eukaryotic cells. Its regulatory particle (RP) initiates the degradation of ubiquitin-protein conjugates by unfolding the substrate and translocating it into the proteasome core particle (CP) to be degraded. The RP has 19 subunits, and their pathway of assembly is not understood. Here we show that in the yeast Saccharomyces cerevisiae three proteins are found associated with RP but not with the RP-CP holoenzyme: Nas6, Rpn14 and Hsm3. Mutations in the corresponding genes confer proteasome loss-of-function phenotypes, despite their virtual absence from the holoenzyme. These effects result from deficient RP assembly. Thus, Nas6, Rpn14 and Hsm3 are RP chaperones. The RP contains six ATPases-the Rpt proteins-and each RP chaperone binds to the carboxy-terminal domain of a specific Rpt. We show in an accompanying study that RP assembly is templated through the Rpt C termini, apparently by their insertion into binding pockets in the CP. Thus, RP chaperones may regulate proteasome assembly by directly restricting the accessibility of Rpt C termini to the CP. In addition, competition between the RP chaperones and the CP for Rpt engagement may explain the release of RP chaperones as proteasomes mature.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727592/" 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/PMC2727592/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roelofs, Jeroen -- Park, Soyeon -- Haas, Wilhelm -- Tian, Geng -- McAllister, Fiona E -- Huo, Ying -- Lee, Byung-Hoon -- Zhang, Fan -- Shi, Yigong -- Gygi, Steven P -- Finley, Daniel -- 5F32GM75737-2/GM/NIGMS NIH HHS/ -- GM043601/GM/NIGMS NIH HHS/ -- GM67945/GM/NIGMS NIH HHS/ -- R37 GM043601/GM/NIGMS NIH HHS/ -- R37 GM043601-19/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jun 11;459(7248):861-5. doi: 10.1038/nature08063.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412159" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry/metabolism ; Carrier Proteins/genetics/metabolism ; Conserved Sequence ; Evolution, Molecular ; Holoenzymes/chemistry/metabolism ; Humans ; Models, Molecular ; Molecular Chaperones/genetics/*metabolism ; Mutation ; Phenotype ; Proteasome Endopeptidase Complex/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/genetics/metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism
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  • 83
    Publication Date: 2009-11-13
    Description: Cohesin not only links sister chromatids but also inhibits the transcriptional machinery's interaction with and movement along chromatin. In contrast, replication forks must traverse such cohesin-associated obstructions to duplicate the entire genome in S phase. How this occurs is unknown. Through single-molecule analysis, we demonstrate that the replication factor C (RFC)-CTF18 clamp loader (RFC(CTF18)) controls the velocity, spacing and restart activity of replication forks in human cells and is required for robust acetylation of cohesin's SMC3 subunit and sister chromatid cohesion. Unexpectedly, we discovered that cohesin acetylation itself is a central determinant of fork processivity, as slow-moving replication forks were found in cells lacking the Eco1-related acetyltransferases ESCO1 or ESCO2 (refs 8-10) (including those derived from Roberts' syndrome patients, in whom ESCO2 is biallelically mutated) and in cells expressing a form of SMC3 that cannot be acetylated. This defect was a consequence of cohesin's hyperstable interaction with two regulatory cofactors, WAPL and PDS5A (refs 12, 13); removal of either cofactor allowed forks to progress rapidly without ESCO1, ESCO2, or RFC(CTF18). Our results show a novel mechanism for clamp-loader-dependent fork progression, mediated by the post-translational modification and structural remodelling of the cohesin ring. Loss of this regulatory mechanism leads to the spontaneous accrual of DNA damage and may contribute to the abnormalities of the Roberts' syndrome cohesinopathy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777716/" 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/PMC2777716/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Terret, Marie-Emilie -- Sherwood, Rebecca -- Rahman, Sadia -- Qin, Jun -- Jallepalli, Prasad V -- R01 CA107342/CA/NCI NIH HHS/ -- R01 CA107342-05/CA/NCI NIH HHS/ -- R01 GM094972/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):231-4. doi: 10.1038/nature08550.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907496" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/deficiency/genetics ; Carrier Proteins/genetics/metabolism ; Cell Aging ; Cell Cycle Proteins/chemistry/*metabolism ; Cell Line ; Chromatids/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/deficiency/genetics/*metabolism ; DNA Damage ; DNA Replication/drug effects/*physiology ; Humans ; Mutagens/toxicity ; Nuclear Proteins/genetics/metabolism ; Protein Subunits/metabolism ; Proto-Oncogene Proteins/metabolism ; Replication Protein C/metabolism
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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2009-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Feb 26;457(7233):1057-8. doi: 10.1038/4571057b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242424" target="_blank"〉PubMed〈/a〉
    Keywords: Europe ; *European Union ; *Food, Genetically Modified/standards ; Humans ; *Plants, Genetically Modified ; Politics ; Public Opinion ; *Zea mays/genetics/physiology
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  • 85
    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rockstrom, Johan -- Steffen, Will -- Noone, Kevin -- Persson, Asa -- Chapin, F Stuart 3rd -- Lambin, Eric F -- Lenton, Timothy M -- Scheffer, Marten -- Folke, Carl -- Schellnhuber, Hans Joachim -- Nykvist, Bjorn -- de Wit, Cynthia A -- Hughes, Terry -- van der Leeuw, Sander -- Rodhe, Henning -- Sorlin, Sverker -- Snyder, Peter K -- Costanza, Robert -- Svedin, Uno -- Falkenmark, Malin -- Karlberg, Louise -- Corell, Robert W -- Fabry, Victoria J -- Hansen, James -- Walker, Brian -- Liverman, Diana -- Richardson, Katherine -- Crutzen, Paul -- Foley, Jonathan A -- England -- Nature. 2009 Sep 24;461(7263):472-5. doi: 10.1038/461472a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stockholm Resilience Centre, Stockholm University, Kraftriket 2B, 10691 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779433" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Civilization ; Conservation of Natural Resources/*methods/trends ; *Earth (Planet) ; Ecology/*methods/*trends ; *Ecosystem ; Extinction, Biological ; Fossils ; Green Chemistry Technology/*methods/trends ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Human Activities/history ; Humans ; Nitrogen/metabolism ; Phosphorus/metabolism
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  • 86
    Publication Date: 2009-06-03
    Description: The rapid turnover and exfoliation of mucosal epithelial cells provides an innate defence system against bacterial infection. Nevertheless, many pathogenic bacteria, including Shigella, are able to surmount exfoliation and colonize the epithelium efficiently. Here we show that the Shigella flexneri effector OspE (consisting of OspE1 and OspE2 proteins), which is highly conserved among enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Citrobacter rodentium and Salmonella strains, reinforces host cell adherence to the basement membrane by interacting with integrin-linked kinase (ILK). The number of focal adhesions was augmented along with membrane fraction ILK by ILK-OspE binding. The interaction between ILK and OspE increased cell surface levels of 1 integrin and suppressed phosphorylation of focal adhesion kinase and paxillin, which are required for rapid turnover of focal adhesion in cell motility. Nocodazole-washout-induced focal adhesion disassembly was blocked by expression of OspE. Polarized epithelial cells infected with a Shigella mutant lacking the ospE gene underwent more rapid cell detachment than cells infected with wild-type Shigella. Infection of guinea pig colons with Shigella corroborated the pivotal role of the OspE-ILK interaction in suppressing epithelial detachment, increasing bacterial cell-to-cell spreading, and promoting bacterial colonization. These results indicate that Shigella sustain their infectious foothold by using special tactics to prevent detachment of infected cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Minsoo -- Ogawa, Michinaga -- Fujita, Yukihiro -- Yoshikawa, Yuko -- Nagai, Takeshi -- Koyama, Tomohiro -- Nagai, Shinya -- Lange, Anika -- Fassler, Reinhard -- Sasakawa, Chihiro -- England -- Nature. 2009 May 28;459(7246):578-82. doi: 10.1038/nature07952.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectious Disease Control, International Research Center for Infectious Diseases, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19489119" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD29/metabolism ; Bacterial Outer Membrane Proteins/genetics/metabolism ; Cell Adhesion/drug effects/*physiology ; Cell Polarity ; Colon/microbiology ; Epithelial Cells/cytology/microbiology ; Focal Adhesions/drug effects/*physiology ; Guinea Pigs ; HeLa Cells ; Humans ; Mice ; Nocodazole/pharmacology ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/*metabolism ; Shigella flexneri/pathogenicity/*physiology ; Virulence Factors/deficiency/genetics/metabolism
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  • 87
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    Nature Publishing Group (NPG)
    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Waal, Frans B M -- England -- Nature. 2009 Jul 9;460(7252):175. doi: 10.1038/460175a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Living Links Center, Emory University, 954 N. Gatewood Road, Atlanta, Georgia 30322, USA. dewaal@emory.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587747" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology ; *Biological Evolution ; Cognition/*physiology ; Humans ; Laughter ; Phylogeny ; Selection, Genetic
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  • 88
    Publication Date: 2009-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gross, Michael L -- England -- Nature. 2009 Sep 17;461(7262):340. doi: 10.1038/461340a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759597" target="_blank"〉PubMed〈/a〉
    Keywords: *Chemical Warfare Agents ; Fentanyl/adverse effects/poisoning ; Humans ; *Military Science ; Moscow ; *Warfare/ethics
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  • 89
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    Nature Publishing Group (NPG)
    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theopold, Ulrich -- England -- Nature. 2009 Sep 24;461(7263):486-7. doi: 10.1038/461486a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779443" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Cells/cytology/metabolism ; *Cell Differentiation ; Drosophila melanogaster/*cytology/growth & development/*metabolism ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism ; Humans ; Immune System/cytology ; Larva/cytology/metabolism ; Reactive Oxygen Species/*metabolism ; Signal Transduction
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  • 90
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Feb 19;457(7232):935. doi: 10.1038/457935a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225472" target="_blank"〉PubMed〈/a〉
    Keywords: China ; *Government Regulation ; Humans ; Research Personnel/legislation & jurisprudence/*organization & ; administration/standards ; Societies, Scientific/*legislation & jurisprudence/*organization & administration ; Stem Cell Transplantation/ethics
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  • 91
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rose, Steven -- England -- Nature. 2009 Nov 5;462(7269):35. doi: 10.1038/462035c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890309" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/*genetics ; *Ethics, Research ; Female ; Humans ; Intelligence/*genetics ; Male ; Reproducibility of Results ; *Sex Characteristics
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  • 92
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-03-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rose, Steven -- England -- Nature. 2009 Mar 12;458(7235):146-7. doi: 10.1038/458146c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279610" target="_blank"〉PubMed〈/a〉
    Keywords: *Bioethics ; Continental Population Groups ; Humans ; Intelligence/*genetics
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  • 93
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Feb 19;457(7232):935-6. doi: 10.1038/457935b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225471" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Specimen Banks/economics/*standards ; *Cell Line ; DNA Fingerprinting/economics ; Humans ; Quality Control ; Reproducibility of Results ; *Research Design
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  • 94
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Scott -- Ubel, Peter -- De Vries, Raymond -- England -- Nature. 2009 Jan 29;457(7229):534-5. doi: 10.1038/457534a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Michigan, 300 North Ingalls Street, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177111" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/economics/ethics/*legislation & jurisprudence/standards ; Cost-Benefit Analysis ; Humans ; Informed Consent/ethics ; Patient Rights/*legislation & jurisprudence/*standards ; Risk Assessment ; United States
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  • 95
    Publication Date: 2009-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rose, Steven -- England -- Nature. 2009 Feb 12;457(7231):786-8. doi: 10.1038/457786a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Open University, UK. S.P.R.Rose@open.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212384" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/*genetics ; Humans ; Intelligence/*genetics ; Science/*ethics/*standards ; *Sociology
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  • 96
    Publication Date: 2009-04-03
    Description: Fungal infections represent a serious threat, particularly in immunocompromised patients. Interleukin-1beta (IL-1beta) is a key pro-inflammatory factor in innate antifungal immunity. The mechanism by which the mammalian immune system regulates IL-1beta production after fungal recognition is unclear. Two signals are generally required for IL-1beta production: an NF-kappaB-dependent signal that induces the synthesis of pro-IL-1beta (p35), and a second signal that triggers proteolytic pro-IL-1beta processing to produce bioactive IL-1beta (p17) via Caspase-1-containing multiprotein complexes called inflammasomes. Here we demonstrate that the tyrosine kinase Syk, operating downstream of several immunoreceptor tyrosine-based activation motif (ITAM)-coupled fungal pattern recognition receptors, controls both pro-IL-1beta synthesis and inflammasome activation after cell stimulation with Candida albicans. Whereas Syk signalling for pro-IL-1beta synthesis selectively uses the Card9 pathway, inflammasome activation by the fungus involves reactive oxygen species production and potassium efflux. Genetic deletion or pharmalogical inhibition of Syk selectively abrogated inflammasome activation by C. albicans but not by inflammasome activators such as Salmonella typhimurium or the bacterial toxin nigericin. Nlrp3 (also known as NALP3) was identified as the critical NOD-like receptor family member that transduces the fungal recognition signal to the inflammasome adaptor Asc (Pycard) for Caspase-1 (Casp1) activation and pro-IL-1beta processing. Consistent with an essential role for Nlrp3 inflammasomes in antifungal immunity, we show that Nlrp3-deficient mice are hypersusceptible to Candida albicans infection. Thus, our results demonstrate the molecular basis for IL-1beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gross, Olaf -- Poeck, Hendrik -- Bscheider, Michael -- Dostert, Catherine -- Hannesschlager, Nicole -- Endres, Stefan -- Hartmann, Gunther -- Tardivel, Aubry -- Schweighoffer, Edina -- Tybulewicz, Victor -- Mocsai, Attila -- Tschopp, Jurg -- Ruland, Jurgen -- MC_U117527252/Medical Research Council/United Kingdom -- England -- Nature. 2009 May 21;459(7245):433-6. doi: 10.1038/nature07965. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Str. 22, 81675 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339971" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Candida albicans/*immunology/physiology ; Carrier Proteins/*immunology/*metabolism ; Caspase 1/metabolism ; Enzyme Activation ; Humans ; Inflammation/immunology ; Interleukin-1beta/biosynthesis/immunology ; Intracellular Signaling Peptides and Proteins/antagonists & ; inhibitors/deficiency/genetics/*metabolism ; Macrophages/metabolism ; Mice ; Monocytes/metabolism ; Nigericin/pharmacology ; Potassium/metabolism ; Protein-Tyrosine Kinases/antagonists & inhibitors/deficiency/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; *Signal Transduction
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  • 97
    Publication Date: 2009-06-19
    Description: T-cell acute lymphoblastic leukaemia (T-ALL) is a blood malignancy afflicting mainly children and adolescents. T-ALL patients present at diagnosis with increased white cell counts and hepatosplenomegaly, and are at an increased risk of central nervous system (CNS) relapse. For that reason, T-ALL patients usually receive cranial irradiation in addition to intensified intrathecal chemotherapy. The marked increase in survival is thought to be worth the considerable side-effects associated with this therapy. Such complications include secondary tumours, neurocognitive deficits, endocrine disorders and growth impairment. Little is known about the mechanism of leukaemic cell infiltration of the CNS, despite its clinical importance. Here we show, using T-ALL animal modelling and gene-expression profiling, that the chemokine receptor CCR7 (ref. 5) is the essential adhesion signal required for the targeting of leukaemic T-cells into the CNS. Ccr7 gene expression is controlled by the activity of the T-ALL oncogene Notch1 and is expressed in human tumours carrying Notch1-activating mutations. Silencing of either CCR7 or its chemokine ligand CCL19 (ref. 6) in an animal model of T-ALL specifically inhibits CNS infiltration. Furthermore, murine CNS-targeting by human T-ALL cells depends on their ability to express CCR7. These studies identify a single chemokine-receptor interaction as a CNS 'entry' signal, and open the way for future pharmacological targeting. Targeted inhibition of CNS involvement in T-ALL could potentially decrease the intensity of CNS-targeted therapy, thus reducing its associated short- and long-term complications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750496/" 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/PMC3750496/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buonamici, Silvia -- Trimarchi, Thomas -- Ruocco, Maria Grazia -- Reavie, Linsey -- Cathelin, Severine -- Mar, Brenton G -- Klinakis, Apostolos -- Lukyanov, Yevgeniy -- Tseng, Jen-Chieh -- Sen, Filiz -- Gehrie, Eric -- Li, Mengling -- Newcomb, Elizabeth -- Zavadil, Jiri -- Meruelo, Daniel -- Lipp, Martin -- Ibrahim, Sherif -- Efstratiadis, Argiris -- Zagzag, David -- Bromberg, Jonathan S -- Dustin, Michael L -- Aifantis, Iannis -- 1 P01 CA97403/CA/NCI NIH HHS/ -- P30CA016087/CA/NCI NIH HHS/ -- R01 AI041428/AI/NIAID NIH HHS/ -- R01 AI062765/AI/NIAID NIH HHS/ -- R01 AI072039/AI/NIAID NIH HHS/ -- R01 CA105129/CA/NCI NIH HHS/ -- R01 CA149655/CA/NCI NIH HHS/ -- R01AI072039/AI/NIAID NIH HHS/ -- R01AI41428/AI/NIAID NIH HHS/ -- R01CA105129/CA/NCI NIH HHS/ -- R01CA133379/CA/NCI NIH HHS/ -- R21 CA141399/CA/NCI NIH HHS/ -- R56AI070310/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Jun 18;459(7249):1000-4. doi: 10.1038/nature08020.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and New York University Cancer Institute, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536265" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion ; Cell Line, Tumor ; Central Nervous System/*metabolism/*pathology ; Chemokine CCL19/deficiency/metabolism ; Chemokine CCL21/metabolism ; Humans ; Leukemia, T-Cell/*metabolism/*pathology ; Mice ; Mice, Inbred C57BL ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism/pathology ; Receptor, Notch1/genetics/metabolism ; Receptors, CCR7/deficiency/*metabolism ; *Signal Transduction
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  • 98
    Publication Date: 2009-05-22
    Description: G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases. They are also fascinating molecules from the perspective of membrane-protein structure and biology. Great progress has been made over the past three decades in understanding diverse GPCRs, from pharmacology to functional characterization in vivo. Recent high-resolution structural studies have provided insights into the molecular mechanisms of GPCR activation and constitutive activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967846/" 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/PMC3967846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenbaum, Daniel M -- Rasmussen, Soren G F -- Kobilka, Brian K -- F32 GM082028/GM/NIGMS NIH HHS/ -- R01 GM083118/GM/NIGMS NIH HHS/ -- R01-GM083118/GM/NIGMS NIH HHS/ -- R01-NS28471/NS/NINDS NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):356-63. doi: 10.1038/nature08144.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Palo Alto, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19458711" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Cytoplasm/metabolism ; Humans ; Opsins/chemistry/metabolism ; Protein Conformation ; Receptors, G-Protein-Coupled/*chemistry/*metabolism ; Signal Transduction
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  • 99
    Publication Date: 2009-09-18
    Description: Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance. Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172006/" 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/PMC3172006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, David L -- Thio, Chloe L -- Martin, Maureen P -- Qi, Ying -- Ge, Dongliang -- O'Huigin, Colm -- Kidd, Judith -- Kidd, Kenneth -- Khakoo, Salim I -- Alexander, Graeme -- Goedert, James J -- Kirk, Gregory D -- Donfield, Sharyne M -- Rosen, Hugo R -- Tobler, Leslie H -- Busch, Michael P -- McHutchison, John G -- Goldstein, David B -- Carrington, Mary -- HHSN261200800001E/CO/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 DA004334/DA/NIDA NIH HHS/ -- R01DA004334/DA/NIDA NIH HHS/ -- R01DA013324/DA/NIDA NIH HHS/ -- R01DK60590/DK/NIDDK NIH HHS/ -- R01HD41224/HD/NICHD NIH HHS/ -- R01HL076902/HL/NHLBI NIH HHS/ -- R56 DA004334/DA/NIDA NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2009 Oct 8;461(7265):798-801. doi: 10.1038/nature08463.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University, Division of Infectious Diseases, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759533" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Africa/ethnology ; Europe/ethnology ; Female ; Gene Frequency ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Genotype ; Hepacivirus/drug effects/*immunology/physiology ; Hepatitis C/drug therapy/*genetics/*immunology/virology ; Humans ; Interleukins/*genetics/*immunology ; Male ; Polymorphism, Single Nucleotide/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
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    Nature Publishing Group (NPG)
    Publication Date: 2009-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Feb 12;457(7231):763-4. doi: 10.1038/457763a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212352" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; History, 19th Century ; *Humanism/history ; Humans
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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