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  • Humans  (4,614)
  • Engineering
  • 2005-2009  (4,670)
  • 1
    Keywords: Building construction ; Engineering ; Materials ; Physics
    ISBN: 9781852334277
    Language: English
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  • 2
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    Berlin, Heidelberg : Springer
    Keywords: Electronics ; Engineering ; Nanotechnology
    ISBN: 9783540283089
    Language: English
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  • 3
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    Berlin, Heidelberg : Springer
    Keywords: Computer engineering ; Engineering ; Nanotechnology ; Optical materials ; Physical optics ; Quantum optics
    ISBN: 9783540469360
    Language: English
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  • 4
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    Berlin, Heidelberg : Springer
    Keywords: Condensed matter ; Engineering ; Optical materials ; Surfaces (Physics)
    ISBN: 9783540264620
    Language: English
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  • 5
    Keywords: Engineering ; Materials
    ISBN: 9781402085840
    Language: English
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  • 6
    Keywords: Electronics ; Engineering ; Optical materials ; Spectrum analysis
    ISBN: 9783540274124
    Language: English
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  • 7
    Keywords: Chemistry, Physical organic ; Engineering ; Nanotechnology ; Optical materials ; Physics
    ISBN: 9783540687528
    Language: English
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  • 8
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    Berlin, Heidelberg : Springer
    Keywords: Electronics ; Engineering ; Optical materials ; Physical optics
    ISBN: 9783540718925
    Language: English
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  • 9
    Keywords: Condensed matter ; Engineering ; Optical materials
    ISBN: 9783540734567
    Language: English
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    Berlin, Heidelberg : Springer
    Keywords: Condensed matter ; Engineering ; Nanotechnology
    ISBN: 9783540375784
    Language: English
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    New York, NY : Springer
    Keywords: Engineering ; Optical materials ; Physical optics
    ISBN: 9780387748016
    Language: English
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  • 12
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    Berlin, Heidelberg : Springer
    Keywords: Analytical biochemistry ; Chemistry ; Chemistry, Physical organic ; Engineering
    ISBN: 9783540745983
    Language: English
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  • 13
    Keywords: Chemistry, Physical organic ; Chemistry, inorganic ; Condensed matter ; Engineering ; Materials ; Structural control (Engineering)
    ISBN: 9781402034718
    Language: English
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  • 14
    Keywords: Condensed matter ; Engineering ; Engineering design ; Materials ; Physics
    ISBN: 9780387345659
    Language: English
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  • 15
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    Berlin, Heidelberg : Springer
    Keywords: Engineering ; Magnetism ; Nanotechnology ; Optical materials
    ISBN: 9783540493365
    Language: English
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    Berlin, Heidelberg : Springer
    Keywords: Chemistry, Physical organic ; Condensed matter ; Engineering ; Optical materials
    ISBN: 9783540712954
    Language: English
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  • 17
    Keywords: Engineering ; Optical materials ; Particles (Nuclear physics) ; Physical optics ; Polymers
    ISBN: 9783540719236
    Language: English
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  • 18
    Keywords: Engineering ; Laser physics ; Microwaves ; Optical materials ; Physical optics
    ISBN: 9780387686172
    Language: English
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  • 19
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    Dordrecht : Springer
    Keywords: Chemicals ; Safety measures ; Engineering ; Materials ; Polymers
    ISBN: 9781402053566
    Language: English
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  • 20
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    Boston, MA : Springer US
    Keywords: Chemistry ; Engineering ; Materials ; Mechanical engineering ; Surfaces (Physics)
    ISBN: 9780387476858
    Language: English
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  • 21
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    Totowa, NJ : Humana Press
    Keywords: Biochemical engineering ; Biotechnology ; Chemical engineering ; Engineering ; Environmental sciences ; Microbiology
    ISBN: 9781592599967
    Language: English
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  • 22
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    Berlin, Heidelberg : Springer
    Keywords: Analytical biochemistry ; Biotechnology ; Engineering ; Food science ; Medical laboratories
    ISBN: 9783540457435
    Language: English
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  • 23
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    Boston, MA : Springer
    Keywords: Engineering ; Machinery ; Materials
    ISBN: 9780387725284
    Language: English
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  • 24
    Keywords: Electronics ; Engineering ; Nanotechnology ; Optical materials ; System safety
    ISBN: 9783540269458
    Language: English
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  • 25
    Keywords: Biochemistry ; Chemistry, Physical organic ; Engineering ; Life sciences ; Nanotechnology ; Physical optics
    ISBN: 9783540284727
    Language: English
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  • 26
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    Berlin, Heidelberg : Springer
    Keywords: Chemistry ; Mathematics ; Engineering ; Operations research ; Systems theory
    ISBN: 9783540488804
    Language: English
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  • 27
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    Berlin, Heidelberg : Springer
    Keywords: Condensed matter ; Engineering ; Magnetism ; Materials ; Nanotechnology
    ISBN: 9783540495765
    Language: English
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    Berlin, Heidelberg : Springer
    Keywords: Engineering ; Optical materials ; Particles (Nuclear physics) ; Physical optics
    ISBN: 9783540745297
    Language: English
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  • 29
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    Berlin, Heidelberg : Springer
    Keywords: Chemistry, Physical organic ; Engineering ; Nanotechnology ; Surfaces (Physics)
    ISBN: 9783540745518
    Language: English
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  • 30
    Keywords: Condensed matter ; Engineering ; Materials ; Nanotechnology ; Optical materials
    ISBN: 9781402035623
    Language: English
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    Berlin, Heidelberg : Springer
    Keywords: Condensed matter ; Engineering ; Nanotechnology
    ISBN: 9783540726753
    Language: English
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  • 32
    Keywords: Electronics ; Engineering ; Nanotechnology ; Thermodynamics
    ISBN: 9783540736073
    Language: English
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  • 33
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    Berlin, Heidelberg : Springer
    Keywords: Crystallography ; Engineering ; Particles (Nuclear physics) ; Surfaces (Physics)
    Edition: Third Edition
    ISBN: 9783540738862
    Language: English
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  • 34
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    Berlin, Heidelberg : Springer
    Keywords: Condensed matter ; Engineering ; Nanotechnology ; Surfaces (Physics)
    ISBN: 9783540343158
    Language: English
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    Berlin, Heidelberg : Springer
    Keywords: Condensed matter ; Engineering ; Materials ; Nanotechnology ; Optical materials
    ISBN: 9783540401865
    Language: English
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  • 36
    Keywords: Chemistry, inorganic ; Engineering ; Materials
    ISBN: 9783540687580
    Language: English
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  • 37
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    Berlin, Heidelberg : Springer
    Keywords: Chemistry, inorganic ; Condensed matter ; Engineering ; Nanotechnology ; Surfaces (Physics)
    ISBN: 9783540368076
    Language: English
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  • 38
    Keywords: Engineering ; Materials ; Materials ; Materials ; Mechanics ; Nuclear engineering
    ISBN: 9781402053290
    Language: English
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  • 39
    Keywords: Electromagnetism ; Engineering ; Laser physics ; Remote sensing
    ISBN: 9781402065033
    Language: English
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  • 40
    Keywords: Engineering ; Optical materials ; Physical optics
    ISBN: 9781402084256
    Language: English
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  • 41
    Keywords: Computer science ; Engineering ; Materials ; Nuclear engineering ; Thermodynamics
    ISBN: 9781402084225
    Language: English
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  • 42
    Keywords: Chemistry ; Engineering ; Magnetism ; Materials ; Optical materials
    ISBN: 9781402087967
    Language: English
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  • 43
    Keywords: Condensed matter ; Engineering ; Materials ; Nanotechnology ; Optical materials
    ISBN: 9781402089039
    Language: English
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  • 44
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    Berlin, Heidelberg : Springer
    Keywords: Engineering ; Nanotechnology ; Particles (Nuclear physics)
    ISBN: 9783540745570
    Language: English
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  • 45
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    Boston, MA : Kluwer Academic Publishers
    Keywords: Engineering ; Materials
    ISBN: 9781402081330
    Language: English
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  • 46
    Publication Date: 2022-05-25
    Description: The primary objective of this publication is to share with a wider audience the valuable information and extensive dialogue that took place amongst over 140 individuals who attended the second in a series of planned workshops on the science and management of coastal landforms in Massachusetts. This workshop took place at the Woods Hole Oceanographic Institution on January 24, 2001. The individuals who attended this workshop are actively engaged in planning, managing, regulating, engineering, educating, and studying coastal landforms and their beneficial functions. This workshop titled, Can Humans & Coastal Landforms Co-exist?’, was a natural follow-up to a previous workshop, Coastal Landform Management in Massachusetts, held at WHOI October 9-10, 1997 (proceedings published as WHOI Technical Report #WHOI-98-16). The workshop had a very practical, applied focus, providing state-of-the-art scientific understanding of coastal landform function, case history management and regulation of human activities proposed on coastal landforms, a multi-faceted mock conservation commission hearing presented by practicing technical consultants and attorneys that involved all attendees acting as regulators in breakout sessions, and, at the conclusion of the workshop, an open discussion on all issues related to the science and management of coastal landforms, including future research needs.
    Description: Funding for these proceedings was provided by WHOI Sea Grant and the NOAA National Sea Grant College Program Office, Department of Commerce, under NOAA Grant No. M10-2, Woods Hole Oceanographic Institution Sea Grant Project No. NA86R60075.
    Keywords: Coastal ; Landforms ; Humans
    Repository Name: Woods Hole Open Access Server
    Type: Technical Report
    Format: 1574993 bytes
    Format: application/pdf
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  • 47
    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
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 48
    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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  • 49
    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
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 50
    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
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 51
    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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  • 52
    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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  • 53
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lok, Corie -- England -- Nature. 2008 Aug 7;454(7205):686-9. doi: 10.1038/454686a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18685675" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/organization & administration ; Boston ; Humans ; Leadership ; Research/economics/*organization & administration/trends ; Schools, Medical/organization & administration/trends ; Universities/economics/*organization & administration/trends
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  • 54
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chouard, Tanguy -- England -- Nature. 2008 Nov 20;456(7220):300-3. doi: 10.1038/456300a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020592" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Computer Simulation ; Gene Regulatory Networks/genetics/physiology ; Genetic Engineering ; *Genetic Variation ; *Growth and Development/genetics/physiology ; Homeodomain Proteins/genetics/metabolism ; Humans ; *Models, Biological ; Sea Urchins/genetics/growth & development ; Trans-Activators/genetics/metabolism ; Yeasts/genetics/metabolism
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  • 55
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shadan, Sadaf -- England -- Nature. 2008 Mar 20;452(7185):296. doi: 10.1038/452296b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354470" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anthelmintics/*pharmacology/therapeutic use/toxicity ; Antioxidants/metabolism ; Cell Line ; *Drug Evaluation, Preclinical ; Drug Resistance ; Humans ; Mice ; Oxadiazoles/*pharmacology/toxicity ; Praziquantel/pharmacology/therapeutic use/toxicity ; Schistosoma mansoni/drug effects/metabolism ; Schistosomiasis/*drug therapy/*parasitology
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  • 56
    Publication Date: 2008-11-28
    Description: Major histocompatibility complex (MHC) class II alleles HLA-DQ8 and the mouse homologue I-A(g7) lacking a canonical aspartic acid residue at position beta57 are associated with coeliac disease and type I diabetes. However, the role of this single polymorphism in disease initiation and progression remains poorly understood. The lack of Asp 57 creates a positively charged P9 pocket, which confers a preference for negatively charged peptides. Gluten lacks such peptides, but tissue transglutaminase (TG2) introduces negatively charged residues at defined positions into gluten T-cell epitopes by deamidating specific glutamine residues on the basis of their spacing to proline residues. The commonly accepted model, proposing that HLA-DQ8 simply favours binding of negatively charged peptides, does not take into account the fact that TG2 requires inflammation for activation and that T-cell responses against native gluten peptides are found, particularly in children. Here we show that beta57 polymorphism promotes the recruitment of T-cell receptors bearing a negative signature charge in the complementary determining region 3beta (CDR3beta) during the response against native gluten peptides presented by HLA-DQ8 in coeliac disease. These T cells showed a crossreactive and heteroclitic (stronger) response to deamidated gluten peptides. Furthermore, gluten peptide deamidation extended the T-cell-receptor repertoire by relieving the requirement for a charged residue in CDR3beta. Thus, the lack of a negative charge at position beta57 in MHC class II was met by negatively charged residues in the T-cell receptor or in the peptide, the combination of which might explain the role of HLA-DQ8 in amplifying the T-cell response against dietary gluten.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784325/" 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/PMC3784325/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hovhannisyan, Zaruhi -- Weiss, Angela -- Martin, Alexandra -- Wiesner, Martina -- Tollefsen, Stig -- Yoshida, Kenji -- Ciszewski, Cezary -- Curran, Shane A -- Murray, Joseph A -- David, Chella S -- Sollid, Ludvig M -- Koning, Frits -- Teyton, Luc -- Jabri, Bana -- DK42086/DK/NIDDK NIH HHS/ -- DK55037/DK/NIDDK NIH HHS/ -- DK67180/DK/NIDDK NIH HHS/ -- R01 DK067180/DK/NIDDK NIH HHS/ -- R01 DK067180-04/DK/NIDDK NIH HHS/ -- England -- Nature. 2008 Nov 27;456(7221):534-8. doi: 10.1038/nature07524.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Pathology, Pediatrics and Committee of Immunology, University of Chicago, Chicago, Illinois 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19037317" target="_blank"〉PubMed〈/a〉
    Keywords: Amides/chemistry ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; Celiac Disease/*genetics/*immunology ; Complementarity Determining Regions/chemistry/immunology ; Cross Reactions ; Epitopes, T-Lymphocyte/chemistry/immunology ; Gliadin/chemistry/immunology ; Glutens/chemistry/*immunology ; HLA-DQ Antigens/chemistry/*genetics/immunology ; Humans ; Hybridomas/immunology ; Mice ; Mice, Transgenic ; Polymorphism, Genetic/*genetics ; Receptors, Antigen, T-Cell/chemistry/immunology ; Static Electricity
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  • 57
    Publication Date: 2008-09-05
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819144/" 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/PMC2819144/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, Doug -- Costanzo, Maria -- Fey, Petra -- Gojobori, Takashi -- Hannick, Linda -- Hide, Winston -- Hill, David P -- Kania, Renate -- Schaeffer, Mary -- St Pierre, Susan -- Twigger, Simon -- White, Owen -- Rhee, Seung Yon -- P41 HG002659/HG/NHGRI NIH HHS/ -- P41 HG002659-07/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Sep 4;455(7209):47-50. doi: 10.1038/455047a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Zebrafish Information Network, 5291 University of Oregon, Eugene, Oregon 97403-5291, USA. dhowe@cs.uoregon.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18769432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Science Disciplines/*methods/*trends ; Career Choice ; Computational Biology/education/methods/*trends ; Databases, Factual/*trends/utilization ; Education, Graduate ; Humans ; Information Storage and Retrieval/methods/*trends ; Internet/*trends/utilization ; Publishing/trends
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Jun 26;453(7199):1148-9. doi: 10.1038/4531148a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18580905" target="_blank"〉PubMed〈/a〉
    Keywords: California ; Genetic Testing/*legislation & jurisprudence ; Humans ; Marketing/legislation & jurisprudence ; Referral and Consultation/legislation & jurisprudence ; *State Government
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  • 59
    Publication Date: 2008-09-30
    Description: Ca(2+)-release-activated Ca(2+) (CRAC) channels underlie sustained Ca(2+) signalling in lymphocytes and numerous other cells after Ca(2+) liberation from the endoplasmic reticulum (ER). RNA interference screening approaches identified two proteins, Stim and Orai, that together form the molecular basis for CRAC channel activity. Stim senses depletion of the ER Ca(2+) store and physically relays this information by translocating from the ER to junctions adjacent to the plasma membrane, and Orai embodies the pore of the plasma membrane calcium channel. A close interaction between Stim and Orai, identified by co-immunoprecipitation and by Forster resonance energy transfer, is involved in the opening of the Ca(2+) channel formed by Orai subunits. Most ion channels are multimers of pore-forming subunits surrounding a central channel, which are preassembled in the ER and transported in their final stoichiometry to the plasma membrane. Here we show, by biochemical analysis after cross-linking in cell lysates and intact cells and by using non-denaturing gel electrophoresis without cross-linking, that Orai is predominantly a dimer in the plasma membrane under resting conditions. Moreover, single-molecule imaging of green fluorescent protein (GFP)-tagged Orai expressed in Xenopus oocytes showed predominantly two-step photobleaching, again consistent with a dimeric basal state. In contrast, co-expression of GFP-tagged Orai with the carboxy terminus of Stim as a cytosolic protein to activate the Orai channel without inducing Ca(2+) store depletion or clustering of Orai into punctae yielded mostly four-step photobleaching, consistent with a tetrameric stoichiometry of the active Orai channel. Interaction with the C terminus of Stim thus induces Orai dimers to dimerize, forming tetramers that constitute the Ca(2+)-selective pore. This represents a new mechanism in which assembly and activation of the functional ion channel are mediated by the same triggering molecule.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597643/" 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/PMC2597643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Penna, Aubin -- Demuro, Angelo -- Yeromin, Andriy V -- Zhang, Shenyuan L -- Safrina, Olga -- Parker, Ian -- Cahalan, Michael D -- P30 CA062203/CA/NCI NIH HHS/ -- R37 NS014609/NS/NINDS NIH HHS/ -- R37 NS014609-29/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Nov 6;456(7218):116-20. doi: 10.1038/nature07338. Epub 2008 Sep 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of California Irvine, California 92697-4561, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18820677" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium Channels/*chemistry/genetics/*metabolism ; Cell Line ; Cross-Linking Reagents ; Drosophila Proteins/*chemistry/genetics/*metabolism ; Drosophila melanogaster/*chemistry/*metabolism ; Humans ; Membrane Proteins/*chemistry/genetics/*metabolism ; Oocytes/metabolism ; Photobleaching ; Protein Multimerization ; Protein Structure, Quaternary ; Xenopus ; Xenopus Proteins/*chemistry/genetics/*metabolism
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  • 60
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shadan, Sadaf -- England -- Nature. 2008 Mar 6;452(7183):39. doi: 10.1038/452039a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18322520" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Cell Differentiation ; Cell Lineage ; Child, Preschool ; Female ; Humans ; Lamin Type A ; Mesenchymal Stromal Cells/pathology ; Nuclear Proteins/genetics/metabolism ; Progeria/metabolism/*pathology/*physiopathology ; Protein Precursors/genetics/metabolism
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  • 61
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    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 May 8;453(7192):160-2. doi: 10.1038/453160a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464725" target="_blank"〉PubMed〈/a〉
    Keywords: Auditory Perception/physiology ; Brain/physiology ; History, 18th Century ; History, 20th Century ; History, Ancient ; History, Medieval ; Humans ; Mathematics ; *Music/history/psychology ; *Science/history
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  • 62
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    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Jun 12;453(7197):830-1. doi: 10.1038/453830a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics/*organization & administration ; Drug Evaluation, Preclinical ; Dynamins/antagonists & inhibitors ; Humans ; Intellectual Property ; Patents as Topic ; Research Personnel/economics ; *Technology Transfer
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  • 63
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    Publication Date: 2008-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pera, Martin F -- England -- Nature. 2008 Jan 10;451(7175):135-6. doi: 10.1038/451135a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18185576" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Differentiation ; Embryonic Stem Cells/*cytology/metabolism ; Fetus/cytology ; Fibroblasts/cytology ; HMGB Proteins/genetics/metabolism ; Humans ; Kruppel-Like Transcription Factors/genetics/metabolism ; Mice ; Octamer Transcription Factor-3/genetics/metabolism ; Pluripotent Stem Cells/*cytology/*metabolism ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; SOXB1 Transcription Factors ; Transcription Factors/genetics/metabolism
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  • 64
    Publication Date: 2008-07-25
    Description: Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This in turn produces long-term changes in the structure of the affected organs and substantial abnormalities in their function. It is therefore important to understand the characteristics and consequences of acute and chronic allergic inflammation, and in particular to explore how mast cells can contribute to several features of this maladaptive pattern of immunological reactivity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573758/" 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/PMC3573758/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galli, Stephen J -- Tsai, Mindy -- Piliponsky, Adrian M -- R01 AI023990/AI/NIAID NIH HHS/ -- R01 AI023990-20/AI/NIAID NIH HHS/ -- R01 AI070813/AI/NIAID NIH HHS/ -- R01 AI070813-01/AI/NIAID NIH HHS/ -- R01 CA072074/CA/NCI NIH HHS/ -- R01 CA072074-15/CA/NCI NIH HHS/ -- England -- Nature. 2008 Jul 24;454(7203):445-54. doi: 10.1038/nature07204.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA. sgalli@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650915" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/immunology ; Animals ; Chronic Disease ; Epithelium/immunology ; Humans ; Hypersensitivity/genetics/*immunology/*pathology ; Immunoglobulin E/immunology ; Inflammation/genetics/*immunology/*pathology
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  • 65
    Publication Date: 2008-06-24
    Description: The transcription factor IRF4 (interferon regulatory factor 4) is required during an immune response for lymphocyte activation and the generation of immunoglobulin-secreting plasma cells. Multiple myeloma, a malignancy of plasma cells, has a complex molecular aetiology with several subgroups defined by gene expression profiling and recurrent chromosomal translocations. Moreover, the malignant clone can sustain multiple oncogenic lesions, accumulating genetic damage as the disease progresses. Current therapies for myeloma can extend survival but are not curative. Hence, new therapeutic strategies are needed that target molecular pathways shared by all subtypes of myeloma. Here we show, using a loss-of-function, RNA-interference-based genetic screen, that IRF4 inhibition is toxic to myeloma cell lines, regardless of transforming oncogenic mechanism. Gene expression profiling and genome-wide chromatin immunoprecipitation analysis uncovered an extensive network of IRF4 target genes and identified MYC as a direct target of IRF4 in activated B cells and myeloma. Unexpectedly, IRF4 was itself a direct target of MYC transactivation, generating an autoregulatory circuit in myeloma cells. Although IRF4 is not genetically altered in most myelomas, they are nonetheless addicted to an aberrant IRF4 regulatory network that fuses the gene expression programmes of normal plasma cells and activated B cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542904/" 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/PMC2542904/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaffer, Arthur L -- Emre, N C Tolga -- Lamy, Laurence -- Ngo, Vu N -- Wright, George -- Xiao, Wenming -- Powell, John -- Dave, Sandeep -- Yu, Xin -- Zhao, Hong -- Zeng, Yuxin -- Chen, Bangzheng -- Epstein, Joshua -- Staudt, Louis M -- CA113992/CA/NCI NIH HHS/ -- CA97513/CA/NCI NIH HHS/ -- R01 CA113992/CA/NCI NIH HHS/ -- R01 CA113992-02/CA/NCI NIH HHS/ -- R33 CA097513-03/CA/NCI NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- England -- Nature. 2008 Jul 10;454(7201):226-31. doi: 10.1038/nature07064. Epub 2008 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18568025" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism/pathology ; Cell Survival ; Cell Transformation, Neoplastic/genetics ; Cells, Cultured ; Chromatin Immunoprecipitation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, myc/genetics ; Humans ; Interferon Regulatory Factors/deficiency/genetics/*metabolism ; Mice ; Multiple Myeloma/genetics/*metabolism/*pathology ; Proto-Oncogene Proteins c-myc/metabolism ; RNA Interference ; Transcriptional Activation
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 May 8;453(7192):140-1. doi: 10.1038/453140a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464702" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Use Alternatives/statistics & numerical data/*trends ; Animals ; Computer Simulation/utilization ; General Surgery/*education ; Humans ; Manikins ; *Plastics ; *Schools, Medical/ethics ; *Swine/surgery ; User-Computer Interface
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  • 67
    Publication Date: 2008-10-03
    Description: Bacterial virulence determinants can be identified, according to the molecular Koch's postulates, if inactivation of a gene associated with a suspected virulence trait results in a loss in pathogenicity. This approach is commonly used with genetically tractable organisms. However, the current lack of tools for targeted gene disruptions in obligate intracellular microbial pathogens seriously hampers the identification of their virulence factors. Here we demonstrate an approach to studying potential virulence factors of genetically intractable organisms, such as Chlamydia. Heterologous expression of Chlamydia pneumoniae CopN in yeast and mammalian cells resulted in a cell cycle arrest, presumably owing to alterations in the microtubule cytoskeleton. A screen of a small molecule library identified two compounds that alleviated CopN-induced growth inhibition in yeast. These compounds interfered with C. pneumoniae replication in mammalian cells, presumably by 'knocking out' CopN function, revealing an essential role of CopN in the support of C. pneumoniae growth during infection. This work demonstrates the role of a specific chlamydial protein in virulence. The chemical biology approach described here can be used to identify virulence factors, and the reverse chemical genetic strategy can result in the identification of lead compounds for the development of novel therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673727/" 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/PMC2673727/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jin -- Lesser, Cammie F -- Lory, Stephen -- R01 AI064285/AI/NIAID NIH HHS/ -- R01 AI064285-03/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Nov 6;456(7218):112-5. doi: 10.1038/nature07355. Epub 2008 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18830244" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/antagonists & inhibitors/genetics/*metabolism ; Cell Cycle ; Cell Line ; Chlamydophila pneumoniae/drug effects/genetics/*growth & ; development/*pathogenicity ; Gene Expression ; Genes, Essential ; Heterocyclic Compounds with 4 or More Rings/pharmacology ; Humans ; Intracellular Space/*microbiology ; Microtubules/metabolism ; Saccharomyces cerevisiae/cytology/drug effects/genetics/metabolism ; Virulence/drug effects ; Virulence Factors/antagonists & inhibitors/genetics/*metabolism
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  • 68
    Publication Date: 2008-12-17
    Description: Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758999/" 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/PMC3758999/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Malaria Genomic Epidemiology Network -- 076934/Wellcome Trust/United Kingdom -- 077383/Wellcome Trust/United Kingdom -- 077383/Z/05/Z/Wellcome Trust/United Kingdom -- G0200454/Medical Research Council/United Kingdom -- G0200454(62635)/Medical Research Council/United Kingdom -- G0600230/Medical Research Council/United Kingdom -- G0600230(77610)/Medical Research Council/United Kingdom -- G0600718/Medical Research Council/United Kingdom -- G19/9/Medical Research Council/United Kingdom -- England -- Nature. 2008 Dec 11;456(7223):732-7. doi: 10.1038/nature07632.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Buea, PO Box 63, Buea, South West Province, Cameroon.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19079050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/genetics ; Epidemiologic Research Design ; Genome, Human/*genetics ; Genome-Wide Association Study ; Global Health ; Humans ; Immunity, Innate/genetics ; Malaria/*epidemiology/*genetics ; Plasmodium/genetics ; Polymorphism, Single Nucleotide
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  • 69
    Publication Date: 2008-06-13
    Description: The 'certainty effect' is a notable violation of expected utility theory by decision makers. It shows that people's tendency to select the safer of two prospects increases when this prospect provides a good outcome with certainty (for example, people prefer a monetary gain of 3 with certainty over 4 with a probability of 0.8, but do not prefer 3 with a probability of 0.25 over 4 with a probability of 0.2). Subsequent work on experience-based decision making in rats extended the certainty effect to other animals, suggesting its generality across different species and different decision-making mechanisms. However, an attempt to replicate this study with human subjects showed a surprising 'reversed certainty effect', namely, the tendency to prefer the safer option decreases when this prospect is associated with certainty (and people now prefer 4 with a probability of 0.8 over 3 with certainty). Here we show that these conflicting results can be explained by perceptual noise and that the certainty effect can be restored experimentally by reducing perceptual accuracy. Using complementary experiments in humans and honeybees (Apis mellifera), we show that by manipulating perceptual accuracy in experience-based tasks, both the certainty and the reversed certainty effects can be exhibited by humans and other animals: the certainty effect emerges when it is difficult to discriminate between the different rewards, whereas the reversed certainty effect emerges when discrimination is easy. Our results fit a simple process-based model of matching behaviour, capable of explaining the certainty effect in humans and other animals that make repeated decisions based on experience. This mechanism should probably be distinguished from those involved in the original certainty effect that was exhibited by human subjects in single description-based problems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shafir, Sharoni -- Reich, Taly -- Tsur, Erez -- Erev, Ido -- Lotem, Arnon -- England -- Nature. 2008 Jun 12;453(7197):917-20. doi: 10.1038/nature06841.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉B. Triwaks Bee Research Center, Department of Entomology, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548069" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bees/*physiology ; Choice Behavior/*physiology ; Humans ; Models, Psychological ; Photic Stimulation ; *Reward ; *Risk-Taking ; *Uncertainty
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  • 70
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 May 1;453(7191):9. doi: 10.1038/453009a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18461710" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; Genetic Privacy/*legislation & jurisprudence ; Genetics, Medical/*legislation & jurisprudence ; Genomics/legislation & jurisprudence/trends ; Humans ; Individuality ; *Prejudice ; United States
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  • 71
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    Nature Publishing Group (NPG)
    Publication Date: 2008-01-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shannon, Kevin M -- Le Beau, Michelle M -- England -- Nature. 2008 Jan 17;451(7176):252-3. doi: 10.1038/451252a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Human, Pair 5/*genetics ; Erythroid Cells/cytology/metabolism ; *Genes, Tumor Suppressor ; Genetic Predisposition to Disease/*genetics ; Humans ; *RNA Interference ; Ribosomal Proteins/deficiency/*genetics/metabolism ; Syndrome
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  • 72
    Publication Date: 2008-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Persson, Anders -- England -- Nature. 2008 Oct 23;455(7216):1036. doi: 10.1038/4551036a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948933" target="_blank"〉PubMed〈/a〉
    Keywords: Diagnosis ; Diagnostic Imaging/*methods/*trends ; Humans ; Imaging, Three-Dimensional/trends ; Magnetic Resonance Imaging/trends ; Photography ; Sweden
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  • 73
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Apr 17;452(7189):788. doi: 10.1038/452788b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18431822" target="_blank"〉PubMed〈/a〉
    Keywords: Genetic Counseling/trends ; *Genome, Human ; Genomics/economics/*trends ; History, 21st Century ; Humans ; Individuality ; Male ; Reference Standards ; Sequence Analysis, DNA/economics/*trends ; Time Factors
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  • 74
    Publication Date: 2008-03-14
    Description: Growth factors stimulate cells to take up excess nutrients and to use them for anabolic processes. The biochemical mechanism by which this is accomplished is not fully understood but it is initiated by phosphorylation of signalling proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine-binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2), binds directly and selectively to tyrosine-phosphorylated peptides. We show that binding of phosphotyrosine peptides to PKM2 results in release of the allosteric activator fructose-1,6-bisphosphate, leading to inhibition of PKM2 enzymatic activity. We also provide evidence that this regulation of PKM2 by phosphotyrosine signalling diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Collectively, our results indicate that expression of this phosphotyrosine-binding form of pyruvate kinase is critical for rapid growth in cancer cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christofk, Heather R -- Vander Heiden, Matthew G -- Wu, Ning -- Asara, John M -- Cantley, Lewis C -- R01 GM056203/GM/NIGMS NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- England -- Nature. 2008 Mar 13;452(7184):181-6. doi: 10.1038/nature06667.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337815" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Site ; Animals ; Catalysis ; Cell Line ; Cell Proliferation/drug effects ; Cells/drug effects/metabolism ; HeLa Cells ; Humans ; Lysine/metabolism ; Models, Molecular ; Peptide Library ; Phosphotyrosine/*metabolism ; Protein Binding ; Proteomics ; Pyruvate Kinase/antagonists & inhibitors/*metabolism ; Substrate Specificity
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  • 75
    Publication Date: 2008-03-14
    Description: Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago. How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christofk, Heather R -- Vander Heiden, Matthew G -- Harris, Marian H -- Ramanathan, Arvind -- Gerszten, Robert E -- Wei, Ru -- Fleming, Mark D -- Schreiber, Stuart L -- Cantley, Lewis C -- R01 GM056203/GM/NIGMS NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 13;452(7184):230-3. doi: 10.1038/nature06734.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337823" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/*genetics ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Fructosediphosphates/metabolism ; Gene Expression Regulation, Neoplastic ; Glycolysis ; Humans ; Lactic Acid/metabolism ; Lung Neoplasms/genetics/metabolism/pathology ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms/enzymology/genetics/*metabolism/*pathology ; Oxidative Phosphorylation ; Oxygen Consumption ; Pyruvate Kinase/*genetics/*metabolism ; Pyruvic Acid/metabolism
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  • 76
    Publication Date: 2008-03-21
    Description: One of the most pervasive problems afflicting people throughout the world is inadequate access to clean water and sanitation. Problems with water are expected to grow worse in the coming decades, with water scarcity occurring globally, even in regions currently considered water-rich. Addressing these problems calls out for a tremendous amount of research to be conducted to identify robust new methods of purifying water at lower cost and with less energy, while at the same time minimizing the use of chemicals and impact on the environment. Here we highlight some of the science and technology being developed to improve the disinfection and decontamination of water, as well as efforts to increase water supplies through the safe re-use of wastewater and efficient desalination of sea and brackish water.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shannon, Mark A -- Bohn, Paul W -- Elimelech, Menachem -- Georgiadis, John G -- Marinas, Benito J -- Mayes, Anne M -- England -- Nature. 2008 Mar 20;452(7185):301-10. doi: 10.1038/nature06599.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NSF STC WaterCAMPWS, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. mshannon@uiuc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354474" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/statistics & numerical data/trends ; Conservation of Natural Resources/methods/trends ; Disinfection/methods ; Humans ; Technology/economics/*trends ; Water Purification/economics/*methods ; *Water Supply
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  • 77
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    Publication Date: 2008-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 Apr 10;452(7188):676. doi: 10.1038/452676a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401371" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; *Electromagnetic Fields ; Exercise/physiology ; Humans ; Lie Detection ; Sweat Glands/drug effects/*physiology/*radiation effects ; Sweating/drug effects/physiology
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  • 78
    Publication Date: 2008-08-22
    Description: DNA double-strand breaks (DSBs) are repaired by two principal mechanisms: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR is the most accurate DSB repair mechanism but is generally restricted to the S and G2 phases of the cell cycle, when DNA has been replicated and a sister chromatid is available as a repair template. By contrast, NHEJ operates throughout the cell cycle but assumes most importance in G1 (refs 4, 6). The choice between repair pathways is governed by cyclin-dependent protein kinases (CDKs), with a major site of control being at the level of DSB resection, an event that is necessary for HR but not NHEJ, and which takes place most effectively in S and G2 (refs 2, 5). Here we establish that cell-cycle control of DSB resection in Saccharomyces cerevisiae results from the phosphorylation by CDK of an evolutionarily conserved motif in the Sae2 protein. We show that mutating Ser 267 of Sae2 to a non-phosphorylatable residue causes phenotypes comparable to those of a sae2Delta null mutant, including hypersensitivity to camptothecin, defective sporulation, reduced hairpin-induced recombination, severely impaired DNA-end processing and faulty assembly and disassembly of HR factors. Furthermore, a Sae2 mutation that mimics constitutive Ser 267 phosphorylation complements these phenotypes and overcomes the necessity of CDK activity for DSB resection. The Sae2 mutations also cause cell-cycle-stage specific hypersensitivity to DNA damage and affect the balance between HR and NHEJ. These findings therefore provide a mechanistic basis for cell-cycle control of DSB repair and highlight the importance of regulating DSB resection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635538/" 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/PMC2635538/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huertas, Pablo -- Cortes-Ledesma, Felipe -- Sartori, Alessandro A -- Aguilera, Andres -- Jackson, Stephen P -- A5290/Cancer Research UK/United Kingdom -- LSHG-CT-2005-512113/Cancer Research UK/United Kingdom -- England -- Nature. 2008 Oct 2;455(7213):689-92. doi: 10.1038/nature07215. Epub 2008 Aug 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18716619" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; CDC28 Protein Kinase, S cerevisiae/*metabolism ; Cell Cycle ; Cell Line ; Cell Survival ; Conserved Sequence ; *DNA Breaks, Double-Stranded ; *DNA Repair ; Endodeoxyribonucleases/metabolism ; Endonucleases ; Exodeoxyribonucleases/metabolism ; Humans ; Mutation ; Phosphorylation ; Phosphoserine/metabolism ; Rad52 DNA Repair and Recombination Protein/metabolism ; *Recombination, Genetic ; Saccharomyces cerevisiae/enzymology/*genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism
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  • 79
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    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharp, Paul M -- Hahn, Beatrice H -- England -- Nature. 2008 Oct 2;455(7213):605-6. doi: 10.1038/455605a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Democratic Republic of the Congo/epidemiology ; *Evolution, Molecular ; Genetic Variation/*genetics ; HIV Infections/*epidemiology/*virology ; HIV-1/classification/*genetics/*isolation & purification ; History, 20th Century ; Humans ; Phylogeny
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  • 80
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Dec 11;456(7223):675-6. doi: 10.1038/456675b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19079000" target="_blank"〉PubMed〈/a〉
    Keywords: Databases, Nucleic Acid/legislation & jurisprudence ; Europe ; Genetic Privacy/*legislation & jurisprudence/trends ; Human Rights/*legislation & jurisprudence ; Humans
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  • 81
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hugenholtz, Philip -- Tyson, Gene W -- England -- Nature. 2008 Sep 25;455(7212):481-3. doi: 10.1038/455481a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818648" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; Computational Biology/trends ; *Ecosystem ; *Environmental Microbiology ; Eukaryotic Cells/metabolism ; Evolution, Molecular ; *Genetics, Microbial/methods ; Genome/genetics ; *Genomics/economics/methods/trends ; Humans ; Marine Biology ; Prokaryotic Cells/metabolism ; Sequence Analysis, DNA/economics ; Time Factors ; Viruses/genetics
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  • 82
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaughnessy, John D -- England -- Nature. 2008 Jul 10;454(7201):172-3. doi: 10.1038/454172a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615074" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism/pathology ; Cell Survival ; Cell Transformation, Neoplastic/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics ; Genes, myc/genetics ; Health ; Humans ; Interferon Regulatory Factors/deficiency/genetics/*metabolism ; Multiple Myeloma/genetics/*metabolism/*pathology ; Proto-Oncogene Proteins c-myc/metabolism
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Mar 6;452(7183):6-7. doi: 10.1038/452006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18322484" target="_blank"〉PubMed〈/a〉
    Keywords: Celecoxib ; Confidentiality/*legislation & jurisprudence ; *Drug Industry ; Humans ; *Isoxazoles/adverse effects/pharmacology ; Peer Review, Research/*legislation & jurisprudence ; Periodicals as Topic/*legislation & jurisprudence ; *Pyrazoles/adverse effects/pharmacology ; *Sulfonamides/adverse effects/pharmacology ; United States
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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2008 Feb 7;451(7179):622-6. doi: 10.1038/451622a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256640" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/economics/legislation & jurisprudence ; Female ; Humans ; New Jersey ; *Politics ; Research Embryo Creation/economics/legislation & jurisprudence ; *State Government ; *Stem Cells
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  • 85
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Dec 4;456(7222):545. doi: 10.1038/456545a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052574" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/drug therapy/*epidemiology/*mortality ; Anti-HIV Agents/*supply & distribution ; Child ; *Federal Government ; Female ; Humans ; Politics ; Pregnancy ; *Public Policy ; South Africa/epidemiology
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  • 86
    Publication Date: 2008-11-18
    Description: Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein, which are two of the acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q (refs 3 and 4). More recently, members of the pentraxin family were found to interact with cell-surface Fcgamma receptors (FcgammaR) and activate leukocyte-mediated phagocytosis. Here we describe the structural mechanism for pentraxin's binding to FcgammaR and its functional activation of FcgammaR-mediated phagocytosis and cytokine secretion. The complex structure between human SAP and FcgammaRIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1:1 stoichiometry between SAP and FcgammaRIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for FcgammaR isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for FcgammaR binding and the inhibition of immune-complex-mediated phagocytosis by soluble pentraxins. These results establish antibody-like functions for pentraxins in the FcgammaR pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688732/" 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/PMC2688732/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Jinghua -- Marnell, Lorraine L -- Marjon, Kristopher D -- Mold, Carolyn -- Du Clos, Terry W -- Sun, Peter D -- R01 AI28358/AI/NIAID NIH HHS/ -- T32 AI007538/AI/NIAID NIH HHS/ -- Z01 AI000853-09/Intramural NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):989-92. doi: 10.1038/nature07468. Epub 2008 Nov 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19011614" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Binding, Competitive ; C-Reactive Protein/chemistry/*immunology/*metabolism ; Crystallography, X-Ray ; Cytokines/immunology/secretion ; Humans ; Immunity, Innate/*immunology ; Immunoglobulin G/immunology/metabolism ; Macrophages/cytology/immunology ; Models, Molecular ; Phagocytosis ; Protein Conformation ; Receptors, IgG/chemistry/*immunology/*metabolism ; Serum Amyloid P-Component/chemistry/*immunology/*metabolism
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  • 87
    Publication Date: 2008-05-13
    Description: Sound communication plays a vital role in frog reproduction, in which vocal advertisement is generally the domain of males. Females are typically silent, but in a few anuran species they can produce a feeble reciprocal call or rapping sounds during courtship. Males of concave-eared torrent frogs (Odorrana tormota) have demonstrated ultrasonic communication capacity. Although females of O. tormota have an unusually well-developed vocal production system, it is unclear whether or not they produce calls or are only passive partners in a communication system dominated by males. Here we show that before ovulation, gravid females of O. tormota emit calls that are distinct from males' advertisement calls, having higher fundamental frequencies and harmonics and shorter call duration. In the field and in a quiet, darkened indoor arena, these female calls evoke vocalizations and extraordinarily precise positive phonotaxis (a localization error of 〈1 degrees ), rivalling that of vertebrates with the highest localization acuity (barn owls, dolphins, elephants and humans). The localization accuracy of O. tormota is remarkable in light of their small head size (interaural distance of 〈1 cm), and suggests an additional selective advantage of high-frequency hearing beyond the ability to avoid masking by low-frequency background noise.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Jun-Xian -- Feng, Albert S -- Xu, Zhi-Min -- Yu, Zu-Lin -- Arch, Victoria S -- Yu, Xin-Jian -- Narins, Peter M -- England -- Nature. 2008 Jun 12;453(7197):914-6. doi: 10.1038/nature06719. Epub 2008 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. shenjx@sun5.ibp.ac.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18469804" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; China ; *Courtship ; Female ; Humans ; Male ; Motor Activity/*physiology ; Ranidae/*physiology ; *Sex Characteristics ; Sound ; *Ultrasonics ; Vocalization, Animal/*physiology
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  • 88
    Publication Date: 2008-01-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ball, Philip -- England -- Nature. 2008 Jan 24;451(7177):385. doi: 10.1038/451385a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18216817" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*physiology ; Biological Clocks/physiology ; Electric Stimulation ; *Environment ; Humans ; Intelligence ; Memory/*physiology ; Physarum/cytology/*physiology
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  • 89
    Publication Date: 2008-10-04
    Description: HIV has advanced from high-risk groups such as intravenous drug users to some in the general population, according to comprehensive new data from the south of China. What needs to be done to halt its spread?〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Lin -- Jia, Manhong -- Ma, Yanling -- Yang, Li -- Chen, Zhiwei -- Ho, David D -- Jiang, Yan -- Zhang, Linqi -- England -- Nature. 2008 Oct 2;455(7213):609-11. doi: 10.1038/455609a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yunnan Center for Disease Control and Prevention, Yunnan, People's Republic of China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833270" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; China/epidemiology ; Ethnic Groups/statistics & numerical data ; Female ; HIV Infections/*epidemiology/prevention & control/transmission/virology ; HIV-1/genetics ; Humans ; Male ; Pregnancy ; Prevalence ; Prostitution/statistics & numerical data ; Sentinel Surveillance ; Sex Ratio ; Substance Abuse, Intravenous/epidemiology
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  • 90
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petherick, Anna -- England -- Nature. 2008 Aug 28;454(7208):1042-5. doi: 10.1038/4541042a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756228" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Profiling ; Gene Expression Regulation/genetics ; Genome/*genetics ; Humans ; Mice ; *Models, Genetic ; Oligonucleotide Array Sequence Analysis ; RNA, Untranslated/*biosynthesis/genetics/*metabolism ; *Transcription, Genetic ; Yeasts/genetics
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  • 91
    Publication Date: 2008-10-25
    Description: BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597110/" 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/PMC2597110/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gavathiotis, Evripidis -- Suzuki, Motoshi -- Davis, Marguerite L -- Pitter, Kenneth -- Bird, Gregory H -- Katz, Samuel G -- Tu, Ho-Chou -- Kim, Hyungjin -- Cheng, Emily H-Y -- Tjandra, Nico -- Walensky, Loren D -- 5P01CA92625/CA/NCI NIH HHS/ -- 5R01CA125562/CA/NCI NIH HHS/ -- 5R01CA50239/CA/NCI NIH HHS/ -- K99 HL095929/HL/NHLBI NIH HHS/ -- K99 HL095929-01A1/HL/NHLBI NIH HHS/ -- K99 HL095929-02/HL/NHLBI NIH HHS/ -- R00 HL095929/HL/NHLBI NIH HHS/ -- R01 CA050239/CA/NCI NIH HHS/ -- R01 CA125562/CA/NCI NIH HHS/ -- R01 CA125562-02/CA/NCI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1076-81. doi: 10.1038/nature07396.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948948" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins/chemistry/metabolism ; BH3 Interacting Domain Death Agonist Protein/metabolism ; Cell Line ; *Gene Expression Regulation ; Humans ; Membrane Proteins/chemistry/metabolism ; Mice ; Mutagenesis, Site-Directed ; Mutation/genetics ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Proto-Oncogene Proteins/chemistry/metabolism ; Sequence Alignment ; bcl-2-Associated X Protein/chemistry/*metabolism
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  • 92
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baltimore, David -- England -- Nature. 2008 Apr 17;452(7189):811. doi: 10.1038/452811a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421330" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines/immunology ; Clinical Trials as Topic/*methods/*trends ; Humans
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  • 93
    Publication Date: 2008-03-14
    Description: Genetic data from two or more species provide information about the process of speciation. In their analysis of DNA from humans, chimpanzees, gorillas, orangutans and macaques (HCGOM), Patterson et al. suggest that the apparently short divergence time between humans and chimpanzees on the X chromosome is explained by a massive interspecific hybridization event in the ancestry of these two species. However, Patterson et al. do not statistically test their own null model of simple speciation before concluding that speciation was complex, and--even if the null model could be rejected--they do not consider other explanations of a short divergence time on the X chromosome. These include natural selection on the X chromosome in the common ancestor of humans and chimpanzees, changes in the ratio of male-to-female mutation rates over time, and less extreme versions of divergence with gene flow (see ref. 2, for example). I therefore believe that their claim of hybridization is unwarranted.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakeley, John -- England -- Nature. 2008 Mar 13;452(7184):E3-4; discussion E4. doi: 10.1038/nature06805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA. wakeley@fas.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337768" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/genetics ; Female ; *Genetic Speciation ; Humans ; Male ; *Models, Genetic ; Mutagenesis/genetics ; Pan troglodytes/*genetics ; Phylogeny ; Reproducibility of Results ; Selection, Genetic ; Sex Characteristics ; Time Factors ; X Chromosome/genetics
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  • 94
    Publication Date: 2008-04-04
    Description: Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hung, Rayjean J -- McKay, James D -- Gaborieau, Valerie -- Boffetta, Paolo -- Hashibe, Mia -- Zaridze, David -- Mukeria, Anush -- Szeszenia-Dabrowska, Neonilia -- Lissowska, Jolanta -- Rudnai, Peter -- Fabianova, Eleonora -- Mates, Dana -- Bencko, Vladimir -- Foretova, Lenka -- Janout, Vladimir -- Chen, Chu -- Goodman, Gary -- Field, John K -- Liloglou, Triantafillos -- Xinarianos, George -- Cassidy, Adrian -- McLaughlin, John -- Liu, Geoffrey -- Narod, Steven -- Krokan, Hans E -- Skorpen, Frank -- Elvestad, Maiken Bratt -- Hveem, Kristian -- Vatten, Lars -- Linseisen, Jakob -- Clavel-Chapelon, Francoise -- Vineis, Paolo -- Bueno-de-Mesquita, H Bas -- Lund, Eiliv -- Martinez, Carmen -- Bingham, Sheila -- Rasmuson, Torgny -- Hainaut, Pierre -- Riboli, Elio -- Ahrens, Wolfgang -- Benhamou, Simone -- Lagiou, Pagona -- Trichopoulos, Dimitrios -- Holcatova, Ivana -- Merletti, Franco -- Kjaerheim, Kristina -- Agudo, Antonio -- Macfarlane, Gary -- Talamini, Renato -- Simonato, Lorenzo -- Lowry, Ray -- Conway, David I -- Znaor, Ariana -- Healy, Claire -- Zelenika, Diana -- Boland, Anne -- Delepine, Marc -- Foglio, Mario -- Lechner, Doris -- Matsuda, Fumihiko -- Blanche, Helene -- Gut, Ivo -- Heath, Simon -- Lathrop, Mark -- Brennan, Paul -- G9900432/Medical Research Council/United Kingdom -- R01 CA092039/CA/NCI NIH HHS/ -- England -- Nature. 2008 Apr 3;452(7187):633-7. doi: 10.1038/nature06885.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International Agency for Research on Cancer (IARC), Lyon 69008, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18385738" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Human, Pair 15/*genetics ; Europe ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Lung Neoplasms/*genetics ; Odds Ratio ; Polymorphism, Single Nucleotide/genetics ; Protein Subunits/*genetics ; Receptors, Nicotinic/*genetics
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  • 95
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huron, David -- England -- Nature. 2008 May 22;453(7194):456-7. doi: 10.1038/453456a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Music & Center for Cognitive Science, Ohio State University, Columbus, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497806" target="_blank"〉PubMed〈/a〉
    Keywords: *Cultural Diversity ; *Cultural Evolution ; History, 17th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; *Music/history ; *Neurosciences
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  • 96
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cobb, Matthew -- Coyne, Jerry -- England -- Nature. 2008 Aug 28;454(7208):1049. doi: 10.1038/4541049d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756233" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Religion ; Religion and Psychology ; Religion and Science ; *Science ; Spirituality ; Superstitions
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  • 97
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    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Joel E -- England -- Nature. 2008 Dec 4;456(7222):572-3. doi: 10.1038/456572a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, 1230 York Avenue, New York 10065, USA. cohen@rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052604" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Child Mortality/trends ; *Developing Countries ; Education/economics/*organization & administration/statistics & numerical ; data/*trends ; Female ; Humans ; Population Growth
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2008-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gee, Harriet E -- Camps, Carme -- Buffa, Francesca M -- Colella, Stefano -- Sheldon, Helen -- Gleadle, Jonathan M -- Ragoussis, Jiannis -- Harris, Adrian L -- England -- Nature. 2008 Oct 23;455(7216):E8-9; author reply E9. doi: 10.1038/nature07362.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948893" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/*pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; MicroRNAs/*genetics ; Neoplasm Metastasis/*genetics
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2008-07-04
    Description: Ca(2+)-release-activated Ca(2+) (CRAC) channels generate sustained Ca(2+) signals that are essential for a range of cell functions, including antigen-stimulated T lymphocyte activation and proliferation. Recent studies have revealed that the depletion of Ca(2+) from the endoplasmic reticulum (ER) triggers the oligomerization of stromal interaction molecule 1 (STIM1), the ER Ca(2+) sensor, and its redistribution to ER-plasma membrane (ER-PM) junctions where the CRAC channel subunit ORAI1 accumulates in the plasma membrane and CRAC channels open. However, how the loss of ER Ca(2+) sets into motion these coordinated molecular rearrangements remains unclear. Here we define the relationships among [Ca(2+)](ER), STIM1 redistribution and CRAC channel activation and identify STIM1 oligomerization as the critical [Ca(2+)](ER)-dependent event that drives store-operated Ca(2+) entry. In human Jurkat leukaemic T cells expressing an ER-targeted Ca(2+) indicator, CRAC channel activation and STIM1 redistribution follow the same function of [Ca(2+)](ER), reaching half-maximum at approximately 200 microM with a Hill coefficient of approximately 4. Because STIM1 binds only a single Ca(2+) ion, the high apparent cooperativity suggests that STIM1 must first oligomerize to enable its accumulation at ER-PM junctions. To assess directly the causal role of STIM1 oligomerization in store-operated Ca(2+) entry, we replaced the luminal Ca(2+)-sensing domain of STIM1 with the 12-kDa FK506- and rapamycin-binding protein (FKBP12, also known as FKBP1A) or the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR, also known as FRAP1). A rapamycin analogue oligomerizes the fusion proteins and causes them to accumulate at ER-PM junctions and activate CRAC channels without depleting Ca(2+) from the ER. Thus, STIM1 oligomerization is the critical transduction event through which Ca(2+) store depletion controls store-operated Ca(2+) entry, acting as a switch that triggers the self-organization and activation of STIM1-ORAI1 clusters at ER-PM junctions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712442/" 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/PMC2712442/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luik, Riina M -- Wang, Bin -- Prakriya, Murali -- Wu, Minnie M -- Lewis, Richard S -- R01 GM045374/GM/NIGMS NIH HHS/ -- R01 GM045374-18/GM/NIGMS NIH HHS/ -- T32 AI007290/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Jul 24;454(7203):538-42. doi: 10.1038/nature07065. Epub 2008 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596693" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/*metabolism ; Calcium Channels/*metabolism ; Cell Membrane/metabolism ; Endoplasmic Reticulum/*metabolism ; Humans ; Jurkat Cells ; Membrane Proteins/*chemistry/genetics/*metabolism ; Neoplasm Proteins/*chemistry/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2008-11-14
    Description: Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug response, yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen-ER and tamoxifen-ER complexes directly repress ERBB2 transcription by means of a cis-regulatory element within the ERBB2 gene in human cell lines. We implicate the paired box 2 gene product (PAX2), in a previously unrecognized role, as a crucial mediator of ER repression of ERBB2 by the anti-cancer drug tamoxifen. We show that PAX2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ERBB2 transcription, the outcome of which determines tamoxifen response in breast cancer cells. The repression of ERBB2 by ER-PAX2 links these two breast cancer subtypes and suggests that aggressive ERBB2-positive tumours can originate from ER-positive luminal tumours by circumventing this repressive mechanism. These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920208/" 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/PMC2920208/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hurtado, Antoni -- Holmes, Kelly A -- Geistlinger, Timothy R -- Hutcheson, Iain R -- Nicholson, Robert I -- Brown, Myles -- Jiang, Jie -- Howat, William J -- Ali, Simak -- Carroll, Jason S -- P01CA8011105/CA/NCI NIH HHS/ -- R01 DK074967/DK/NIDDK NIH HHS/ -- R01 DK074967-03/DK/NIDDK NIH HHS/ -- R01DK074967/DK/NIDDK NIH HHS/ -- Cancer Research UK/United Kingdom -- England -- Nature. 2008 Dec 4;456(7222):663-6. doi: 10.1038/nature07483. Epub 2008 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19005469" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/drug therapy/genetics/pathology ; Cell Line ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; Drug Resistance, Neoplasm/genetics ; Estrogens/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Silencing ; Genes, erbB-2/*genetics ; Histone Acetyltransferases ; Humans ; Nuclear Receptor Coactivator 3 ; PAX2 Transcription Factor/deficiency/genetics/*metabolism ; Receptor, ErbB-2/*genetics ; Receptors, Estrogen/*metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; Repressor Proteins/metabolism ; Tamoxifen/metabolism/*pharmacology ; Trans-Activators
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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