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  • Humans  (4,614)
  • Inorganic Chemistry
  • 2005-2009  (4,614)
  • 1
    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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  • 2
    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
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  • 3
    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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  • 4
    Publication Date: 2009-12-17
    Description: Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951497/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951497/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ruiqiang -- Fan, Wei -- Tian, Geng -- Zhu, Hongmei -- He, Lin -- Cai, Jing -- Huang, Quanfei -- Cai, Qingle -- Li, Bo -- Bai, Yinqi -- Zhang, Zhihe -- Zhang, Yaping -- Wang, Wen -- Li, Jun -- Wei, Fuwen -- Li, Heng -- Jian, Min -- Li, Jianwen -- Zhang, Zhaolei -- Nielsen, Rasmus -- Li, Dawei -- Gu, Wanjun -- Yang, Zhentao -- Xuan, Zhaoling -- Ryder, Oliver A -- Leung, Frederick Chi-Ching -- Zhou, Yan -- Cao, Jianjun -- Sun, Xiao -- Fu, Yonggui -- Fang, Xiaodong -- Guo, Xiaosen -- Wang, Bo -- Hou, Rong -- Shen, Fujun -- Mu, Bo -- Ni, Peixiang -- Lin, Runmao -- Qian, Wubin -- Wang, Guodong -- Yu, Chang -- Nie, Wenhui -- Wang, Jinhuan -- Wu, Zhigang -- Liang, Huiqing -- Min, Jiumeng -- Wu, Qi -- Cheng, Shifeng -- Ruan, Jue -- Wang, Mingwei -- Shi, Zhongbin -- Wen, Ming -- Liu, Binghang -- Ren, Xiaoli -- Zheng, Huisong -- Dong, Dong -- Cook, Kathleen -- Shan, Gao -- Zhang, Hao -- Kosiol, Carolin -- Xie, Xueying -- Lu, Zuhong -- Zheng, Hancheng -- Li, Yingrui -- Steiner, Cynthia C -- Lam, Tommy Tsan-Yuk -- Lin, Siyuan -- Zhang, Qinghui -- Li, Guoqing -- Tian, Jing -- Gong, Timing -- Liu, Hongde -- Zhang, Dejin -- Fang, Lin -- Ye, Chen -- Zhang, Juanbin -- Hu, Wenbo -- Xu, Anlong -- Ren, Yuanyuan -- Zhang, Guojie -- Bruford, Michael W -- Li, Qibin -- Ma, Lijia -- Guo, Yiran -- An, Na -- Hu, Yujie -- Zheng, Yang -- Shi, Yongyong -- Li, Zhiqiang -- Liu, Qing -- Chen, Yanling -- Zhao, Jing -- Qu, Ning -- Zhao, Shancen -- Tian, Feng -- Wang, Xiaoling -- Wang, Haiyin -- Xu, Lizhi -- Liu, Xiao -- Vinar, Tomas -- Wang, Yajun -- Lam, Tak-Wah -- Yiu, Siu-Ming -- Liu, Shiping -- Zhang, Hemin -- Li, Desheng -- Huang, Yan -- Wang, Xia -- Yang, Guohua -- Jiang, Zhi -- Wang, Junyi -- Qin, Nan -- Li, Li -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Wong, Gane Ka-Shu -- Olson, Maynard -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):311-7. doi: 10.1038/nature08696. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010809" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; China ; Conserved Sequence/genetics ; Contig Mapping ; Diet/veterinary ; Dogs ; Evolution, Molecular ; Female ; Fertility/genetics/physiology ; Genome/*genetics ; *Genomics ; Heterozygote ; Humans ; Multigene Family/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Synteny/genetics ; Ursidae/classification/*genetics/physiology
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  • 5
    Publication Date: 2009-12-18
    Description: All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145108/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pleasance, Erin D -- Cheetham, R Keira -- Stephens, Philip J -- McBride, David J -- Humphray, Sean J -- Greenman, Chris D -- Varela, Ignacio -- Lin, Meng-Lay -- Ordonez, Gonzalo R -- Bignell, Graham R -- Ye, Kai -- Alipaz, Julie -- Bauer, Markus J -- Beare, David -- Butler, Adam -- Carter, Richard J -- Chen, Lina -- Cox, Anthony J -- Edkins, Sarah -- Kokko-Gonzales, Paula I -- Gormley, Niall A -- Grocock, Russell J -- Haudenschild, Christian D -- Hims, Matthew M -- James, Terena -- Jia, Mingming -- Kingsbury, Zoya -- Leroy, Catherine -- Marshall, John -- Menzies, Andrew -- Mudie, Laura J -- Ning, Zemin -- Royce, Tom -- Schulz-Trieglaff, Ole B -- Spiridou, Anastassia -- Stebbings, Lucy A -- Szajkowski, Lukasz -- Teague, Jon -- Williamson, David -- Chin, Lynda -- Ross, Mark T -- Campbell, Peter J -- Bentley, David R -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- England -- Nature. 2010 Jan 14;463(7278):191-6. doi: 10.1038/nature08658. Epub 2009 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016485" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Cell Line, Tumor ; DNA Damage/genetics ; DNA Mutational Analysis ; DNA Repair/genetics ; Gene Dosage/genetics ; Genes, Neoplasm/*genetics ; Genome, Human/*genetics ; Humans ; Loss of Heterozygosity/genetics ; Male ; Melanoma/etiology/genetics ; MicroRNAs/genetics ; Mutagenesis, Insertional/genetics ; Mutation/*genetics ; Neoplasms/etiology/*genetics ; Polymorphism, Single Nucleotide/genetics ; Precision Medicine ; Sequence Deletion/genetics ; Ultraviolet Rays
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  • 6
    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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  • 7
    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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  • 8
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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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  • 9
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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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  • 10
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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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  • 11
    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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  • 12
    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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  • 13
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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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  • 14
    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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  • 15
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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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  • 16
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    Nature Publishing Group (NPG)
    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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  • 17
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    Nature Publishing Group (NPG)
    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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  • 18
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    Nature Publishing Group (NPG)
    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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  • 19
    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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  • 20
    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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  • 21
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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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  • 22
    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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  • 23
    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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  • 24
    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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  • 25
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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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  • 26
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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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  • 27
    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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  • 28
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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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  • 29
    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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  • 30
    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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  • 31
    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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  • 32
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    Nature Publishing Group (NPG)
    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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  • 33
    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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    Nature Publishing Group (NPG)
    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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  • 35
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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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  • 36
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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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  • 37
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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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  • 38
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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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  • 39
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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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  • 40
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    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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  • 41
    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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  • 42
    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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  • 43
    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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  • 44
    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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  • 45
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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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  • 46
    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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  • 47
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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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  • 48
    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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  • 49
    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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  • 50
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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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  • 51
    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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  • 52
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    Unknown
    Nature Publishing Group (NPG)
    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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  • 53
    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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  • 54
    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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  • 55
    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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  • 56
    Publication Date: 2008-11-14
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685185/" 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/PMC2685185/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bankston, J R -- Kass, R S -- R01 HL056810/HL/NHLBI NIH HHS/ -- R01 HL056810-11/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 Nov 13;456(7219):183-5. doi: 10.1038/456183a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19005542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthropod Venoms/metabolism ; Humans ; Ion Channel Gating/*physiology ; Sodium Channels/*metabolism
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  • 57
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):317-8. doi: 10.1038/456317a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020598" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anniversaries and Special Events ; Biodiversity ; *Biological Evolution ; Epidemiology/trends ; Humans ; Models, Biological ; Mutagenesis ; Religion and Science ; Science/*trends ; Selection, Genetic
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luo, Ji -- Elledge, Stephen J -- England -- Nature. 2008 Jun 19;453(7198):995-6. doi: 10.1038/453995a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Transformation, Neoplastic/*genetics ; Colonic Neoplasms/genetics/pathology ; Gene Expression Regulation, Neoplastic ; Genes, p53/genetics ; Genes, ras/genetics ; Humans ; Models, Biological ; Oncogenes/*genetics
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  • 59
    Publication Date: 2008-10-17
    Description: Understanding the pathogenesis of neuropsychiatric disorders is a substantial challenge for neurobiologists. It has long been hoped that identifying alleles that confer increased risk of such disorders would provide clues for neurobiological investigation. But this quest has been stymied by a lack of validated biological markers for characterizing and distinguishing the different disorders and by the genetic complexity underpinning these diseases. Now, modern genomic technologies have begun to facilitate the discovery of relevant genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hyman, Steven E -- England -- Nature. 2008 Oct 16;455(7215):890-3. doi: 10.1038/nature07454.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Office of the Provost, Harvard University, Department of Neurobiology, Harvard Medical School, Massachusetts Hall, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923510" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; *Mental Disorders/diagnosis/epidemiology/genetics/physiopathology ; *Nervous System Diseases/diagnosis/epidemiology/genetics/physiopathology ; Phenotype
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  • 60
    Publication Date: 2008-01-04
    Description: NUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family. NUMB is also an endocytic protein, and the NOTCH-NUMB counteraction has been linked to this function. There might be, however, additional functions of NUMB, as witnessed by its proposed role as a tumour suppressor in breast cancer. Here we describe a previously unknown function for human NUMB as a regulator of tumour protein p53 (also known as TP53). NUMB enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. This results in increased p53 protein levels and activity, and in regulation of p53-dependent phenotypes. In breast cancers there is frequent loss of NUMB expression. We show that, in primary breast tumour cells, this event causes decreased p53 levels and increased chemoresistance. In breast cancers, loss of NUMB expression causes increased activity of the receptor NOTCH. Thus, in these cancers, a single event-loss of NUMB expression-determines activation of an oncogene (NOTCH) and attenuation of the p53 tumour suppressor pathway. Biologically, this results in an aggressive tumour phenotype, as witnessed by findings that NUMB-defective breast tumours display poor prognosis. Our results uncover a previously unknown tumour suppressor circuitry.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colaluca, Ivan N -- Tosoni, Daniela -- Nuciforo, Paolo -- Senic-Matuglia, Francesca -- Galimberti, Viviana -- Viale, Giuseppe -- Pece, Salvatore -- Di Fiore, Pier Paolo -- England -- Nature. 2008 Jan 3;451(7174):76-80. doi: 10.1038/nature06412.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IFOM, the FIRC Institute for Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172499" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/genetics/metabolism/pathology ; Cell Line, Tumor ; Cells, Cultured ; DNA Damage ; Drug Resistance, Neoplasm ; Gene Silencing ; Humans ; Membrane Proteins/deficiency/genetics/*metabolism ; Nerve Tissue Proteins/deficiency/genetics/*metabolism ; Prognosis ; Protein Binding ; Proto-Oncogene Proteins c-mdm2/metabolism ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitination
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  • 61
    Publication Date: 2008-05-24
    Description: Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like receptor for ubiquitin (Pru) domain, which binds K48-linked diubiquitin with an affinity of approximately 90 nM. Like proteasomal ubiquitin receptor Rpn10/S5a, Rpn13 also binds ubiquitin-like (UBL) domains of UBL-ubiquitin-associated (UBA) proteins. In yeast, a synthetic phenotype results when specific mutations of the ubiquitin binding sites of Rpn10 and Rpn13 are combined, indicating functional linkage between these ubiquitin receptors. Because Rpn13 is also the proteasomal receptor for Uch37, a deubiquitinating enzyme, our findings suggest a coupling of chain recognition and disassembly at the proteasome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839886/" 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/PMC2839886/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Husnjak, Koraljka -- Elsasser, Suzanne -- Zhang, Naixia -- Chen, Xiang -- Randles, Leah -- Shi, Yuan -- Hofmann, Kay -- Walters, Kylie J -- Finley, Daniel -- Dikic, Ivan -- CA097004/CA/NCI NIH HHS/ -- GM008700/GM/NIGMS NIH HHS/ -- GM043601/GM/NIGMS NIH HHS/ -- R01 CA097004/CA/NCI NIH HHS/ -- R01 CA097004-05/CA/NCI NIH HHS/ -- R01 CA097004-06A1/CA/NCI NIH HHS/ -- R37 GM043601/GM/NIGMS NIH HHS/ -- R37 GM043601-17/GM/NIGMS NIH HHS/ -- T32 GM008700/GM/NIGMS NIH HHS/ -- T32 GM008700-09/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 May 22;453(7194):481-8. doi: 10.1038/nature06926.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497817" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites/genetics ; Cell Adhesion Molecules/chemistry/genetics/metabolism ; Humans ; Membrane Glycoproteins/chemistry/genetics/metabolism ; Mice ; Molecular Sequence Data ; Mutation/genetics ; Phenotype ; Proteasome Endopeptidase Complex/*chemistry/genetics/*metabolism ; Protein Subunits/chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; Ubiquitin/*metabolism
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  • 62
    Publication Date: 2008-09-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lupski, James R -- England -- Nature. 2008 Sep 11;455(7210):178-9. doi: 10.1038/455178a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784712" target="_blank"〉PubMed〈/a〉
    Keywords: Gene Dosage/genetics ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Humans ; Models, Genetic ; Polymorphism, Single Nucleotide/genetics ; Psychotic Disorders/genetics ; Schizophrenia/genetics ; Sequence Deletion/*genetics
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  • 63
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):282. doi: 10.1038/456282a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020565" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; *Federal Government ; Humans ; Leadership ; National Institutes of Health (U.S.)/*organization & administration ; *Stem Cells/cytology ; United States
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  • 64
    Publication Date: 2008-05-16
    Description: The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 (ref. 7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collins, Patrick J -- Haire, Lesley F -- Lin, Yi Pu -- Liu, Junfeng -- Russell, Rupert J -- Walker, Philip A -- Skehel, John J -- Martin, Stephen R -- Hay, Alan J -- Gamblin, Steven J -- MC_U117512711/Medical Research Council/United Kingdom -- MC_U117512723/Medical Research Council/United Kingdom -- MC_U117570592/Medical Research Council/United Kingdom -- MC_U117584222/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 Jun 26;453(7199):1258-61. doi: 10.1038/nature06956. Epub 2008 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480754" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Crystallography, X-Ray ; *Drug Resistance, Viral ; Enzyme Inhibitors/chemistry/metabolism/pharmacology ; Humans ; Influenza A Virus, H1N1 Subtype/drug effects/enzymology/genetics ; Influenza A Virus, H5N1 Subtype/*drug effects/*enzymology/genetics ; Influenza, Human/virology ; Kinetics ; Models, Molecular ; Molecular Conformation ; Mutation/*genetics ; Neuraminidase/antagonists & inhibitors/*chemistry/*genetics/metabolism ; Oseltamivir/chemistry/metabolism/*pharmacology ; Protein Binding ; Zanamivir/pharmacology
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  • 65
    Publication Date: 2008-10-04
    Description: The development of a safe and effective human immunodeficiency virus (HIV)-1 vaccine is a critically important global health priority. Despite recent advances in our understanding of HIV-1 pathogenesis and immunology, however, major scientific obstacles remain. Prototype HIV-1 vaccine candidates aimed at eliciting humoral and cellular immune responses have so far failed to protect against HIV-1 infection or to reduce viral loads after infection in clinical efficacy studies. A renewed and coordinated commitment to basic discovery research, preclinical studies and clinical trials will therefore be required to overcome the hurdles currently facing the field. Here I review key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572109/" 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/PMC2572109/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barouch, Dan H -- R01 AI058727/AI/NIAID NIH HHS/ -- R01 AI058727-05/AI/NIAID NIH HHS/ -- R01 AI066924/AI/NIAID NIH HHS/ -- R01 AI066924-03/AI/NIAID NIH HHS/ -- U19 AI066305/AI/NIAID NIH HHS/ -- U19 AI066305-04/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI078526-01/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):613-9. doi: 10.1038/nature07352.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. dbarouch@bidmc.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833271" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Antibody Formation ; Clinical Trials as Topic ; HIV Infections/*immunology/*prevention & control/virology ; HIV-1/classification/genetics/*immunology/physiology ; Humans ; Immunity, Cellular
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 20;456(7220):281-2. doi: 10.1038/456281b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020563" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Welfare/ethics/*legislation & jurisprudence/trends ; Animals ; European Union ; Humans ; *Models, Animal ; Neurosciences/ethics/legislation & jurisprudence/*methods ; Politics ; Primates/*physiology ; *Research Personnel
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  • 67
    Publication Date: 2008-10-17
    Description: Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer. High-risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal. Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non-synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild-type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small-molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling (TUNEL). Short hairpin RNA (shRNA)-mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587486/" 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/PMC2587486/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉George, Rani E -- Sanda, Takaomi -- Hanna, Megan -- Frohling, Stefan -- Luther, William 2nd -- Zhang, Jianming -- Ahn, Yebin -- Zhou, Wenjun -- London, Wendy B -- McGrady, Patrick -- Xue, Liquan -- Zozulya, Sergey -- Gregor, Vlad E -- Webb, Thomas R -- Gray, Nathanael S -- Gilliland, D Gary -- Diller, Lisa -- Greulich, Heidi -- Morris, Stephan W -- Meyerson, Matthew -- Look, A Thomas -- CA21765/CA/NCI NIH HHS/ -- CA69129/CA/NCI NIH HHS/ -- K08 NS047983/NS/NINDS NIH HHS/ -- K08 NS047983-03/NS/NINDS NIH HHS/ -- K08 NS047983-04/NS/NINDS NIH HHS/ -- K08 NS047983-05/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Oct 16;455(7215):975-8. doi: 10.1038/nature07397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923525" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Enzyme Activation/genetics ; Genome, Human/genetics ; Humans ; In Situ Hybridization, Fluorescence ; In Situ Nick-End Labeling ; Mice ; Mutation/*genetics ; Neuroblastoma/enzymology/*genetics/pathology/*therapy ; Polymorphism, Single Nucleotide/genetics ; Protein Structure, Tertiary/genetics ; Protein-Tyrosine Kinases/*antagonists & inhibitors/chemistry/*genetics/metabolism ; Receptor Protein-Tyrosine Kinases ; Sequence Analysis, DNA
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  • 68
    Publication Date: 2008-01-22
    Description: The future paths of population ageing result from specific combinations of declining fertility and increasing life expectancies in different parts of the world. Here we measure the speed of population ageing by using conventional measures and new ones that take changes in longevity into account for the world as a whole and for 13 major regions. We report on future levels of indicators of ageing and the speed at which they change. We show how these depend on whether changes in life expectancy are taken into account. We also show that the speed of ageing is likely to increase over the coming decades and to decelerate in most regions by mid-century. All our measures indicate a continuous ageing of the world's population throughout the century. The median age of the world's population increases from 26.6 years in 2000 to 37.3 years in 2050 and then to 45.6 years in 2100, when it is not adjusted for longevity increase. When increases in life expectancy are taken into account, the adjusted median age rises from 26.6 in 2000 to 31.1 in 2050 and only to 32.9 in 2100, slightly less than what it was in the China region in 2005. There are large differences in the regional patterns of ageing. In North America, the median age adjusted for life expectancy change falls throughout almost the entire century, whereas the conventional median age increases significantly. Our assessment of trends in ageing is based on new probabilistic population forecasts. The probability that growth in the world's population will end during this century is 88%, somewhat higher than previously assessed. After mid-century, lower rates of population growth are likely to coincide with slower rates of ageing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lutz, Wolfgang -- Sanderson, Warren -- Scherbov, Sergei -- England -- Nature. 2008 Feb 7;451(7179):716-9. doi: 10.1038/nature06516. Epub 2008 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉World Population Program, International Institute for Applied Systems Analysis, Schlossplatz 1, A-2361 Laxenburg, Austria. lutz@iiasa.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18204438" target="_blank"〉PubMed〈/a〉
    Keywords: Age Distribution ; Aged ; Aged, 80 and over ; Aging/physiology ; Emigration and Immigration ; *Geography ; Humans ; *Internationality ; Life Expectancy/ethnology/*trends ; Longevity ; Middle Aged ; Mortality/trends ; Population Density ; Time Factors
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  • 69
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pierce, Robin -- Illes, Judy -- England -- Nature. 2008 Jan 31;451(7178):521. doi: 10.1038/451521c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235479" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Enhancement/*ethics/standards ; Cognition/*drug effects ; Humans ; Legislation, Drug ; Pharmaceutical Preparations/economics/supply & distribution
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  • 70
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lynch, Clifford -- England -- Nature. 2008 Sep 4;455(7209):28-9. doi: 10.1038/455028a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Coalition for Networked Information, 21 Dupont Circle, Washington DC 20036, USA. cliff@cni.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18769419" target="_blank"〉PubMed〈/a〉
    Keywords: Archives ; Databases, Factual/economics/standards ; Humans ; Information Management/economics/*methods/organization & ; administration/*standards ; Information Storage and Retrieval/economics/methods/standards ; Research/economics/organization & administration/standards ; *Research Design ; Time Factors
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  • 71
    Publication Date: 2008-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coll-Seck, Awa Marie -- Ghebreyesus, Tedros Adhanom -- Court, Alan -- England -- Nature. 2008 Apr 17;452(7189):810. doi: 10.1038/452810b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421325" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; International Cooperation ; Malaria/economics/epidemiology/*prevention & control/therapy ; Public Health/economics/*trends
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  • 72
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bartram, Jamie -- England -- Nature. 2008 Mar 20;452(7185):283-4. doi: 10.1038/452283a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉WHO's headquarters in Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354459" target="_blank"〉PubMed〈/a〉
    Keywords: Benchmarking ; *Global Health ; Humans ; Internationality ; Sanitation/*economics/standards/*statistics & numerical data/trends ; Social Class ; United Nations ; Water Supply/economics/standards/statistics & numerical data ; World Health Organization
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  • 73
    Publication Date: 2008-11-04
    Description: Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3' untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2593745/" 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/PMC2593745/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Eric T -- Sandberg, Rickard -- Luo, Shujun -- Khrebtukova, Irina -- Zhang, Lu -- Mayr, Christine -- Kingsmore, Stephen F -- Schroth, Gary P -- Burge, Christopher B -- R01 GM085319/GM/NIGMS NIH HHS/ -- R01 GM085319-01/GM/NIGMS NIH HHS/ -- R01 HG002439/HG/NHGRI NIH HHS/ -- R01 HG002439-07/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Nov 27;456(7221):470-6. doi: 10.1038/nature07509.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18978772" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/*genetics ; Base Sequence ; Cell Line ; Exons/genetics ; *Gene Expression Profiling ; Humans ; Open Reading Frames/genetics ; Organ Specificity ; Polyadenylation ; Protein Isoforms/*genetics ; RNA, Messenger/*analysis/*genetics ; RNA-Binding Proteins/metabolism ; Repressor Proteins/metabolism
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  • 74
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barron, Michael -- England -- Nature. 2008 Jun 12;453(7197):859-60. doi: 10.1038/453859a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Architecture and Civil Engineering, University of Bath, BA2 7AY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548056" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; *Acoustics ; Auditory Perception ; *Facility Design and Construction/history ; Hearing/physiology ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; *Music/history
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  • 75
    Publication Date: 2008-08-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Inglis, Stephen -- Wood, John -- Minor, Philip -- England -- Nature. 2008 Aug 21;454(7207):939. doi: 10.1038/454939c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719565" target="_blank"〉PubMed〈/a〉
    Keywords: Drug Industry/organization & administration/standards ; Humans ; Influenza Vaccines/classification/standards/*supply & distribution ; Orthomyxoviridae/physiology ; Orthomyxoviridae Infections/prevention & control ; Time Factors ; Virus Cultivation ; World Health Organization
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  • 76
    Publication Date: 2008-10-14
    Description: Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Sabine -- Renninger, Markus -- Hennenlotter, Jorg -- Wiesner, Tina -- Just, Lothar -- Bonin, Michael -- Aicher, Wilhelm -- Buhring, Hans-Jorg -- Mattheus, Ulrich -- Mack, Andreas -- Wagner, Hans-Joachim -- Minger, Stephen -- Matzkies, Matthias -- Reppel, Michael -- Hescheler, Jurgen -- Sievert, Karl-Dietrich -- Stenzl, Arnulf -- Skutella, Thomas -- England -- Nature. 2008 Nov 20;456(7220):344-9. doi: 10.1038/nature07404. Epub 2008 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Anatomy, Department of Experimental Embryology, Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18849962" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Biomarkers/metabolism ; Cell Culture Techniques ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cells, Cultured ; Embryonic Stem Cells/cytology/metabolism ; Epigenesis, Genetic ; Gene Expression Profiling ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pluripotent Stem Cells/*cytology/metabolism ; Spermatogonia/cytology/ultrastructure ; Teratoma/pathology ; Testis/*cytology
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  • 77
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ings, Simon -- England -- Nature. 2008 Nov 20;456(7220):304-9. doi: 10.1038/456304a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Eye/anatomy & histology ; Humans ; *Ocular Physiological Phenomena
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  • 78
    Publication Date: 2008-02-22
    Description: Despite considerable advances in the treatment of cardiovascular disease, it remains the leading cause of death in developed countries. Assessment of classic cardiovascular risk factors--including high blood pressure, diabetes and smoking--has a central role in disease prevention. However, many individuals with coronary heart disease (a narrowing of the blood vessels that supply the heart) have only one, or none, of the classic risk factors. Thus, new biomarkers are needed to augment the information obtained from traditional indicators and to illuminate disease mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerszten, Robert E -- Wang, Thomas J -- England -- Nature. 2008 Feb 21;451(7181):949-52. doi: 10.1038/nature06802.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital, Cardiology Division, 55 Fruit Street, Boston, Massachusetts 02114, USA. rgerszten@partners.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288185" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers/*analysis ; Cardiovascular System/*metabolism/*physiopathology ; Humans ; Proteomics ; ROC Curve ; Risk Factors ; Transcription, Genetic
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  • 79
    Publication Date: 2008-08-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pitsouli, Chrysoula -- Perrimon, Norbert -- England -- Nature. 2008 Jul 31;454(7204):592-3. doi: 10.1038/454592a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18668098" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; *Cell Proliferation ; Drosophila melanogaster/cytology/*growth & development ; Epithelial Cells/*cytology/metabolism ; Humans ; Intestinal Mucosa/cytology/*growth & development/metabolism ; Signal Transduction
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  • 80
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lynch, Matthew -- England -- Nature. 2008 Apr 17;452(7189):810. doi: 10.1038/452810a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421326" target="_blank"〉PubMed〈/a〉
    Keywords: Humans ; Investments/*trends ; Malaria/*economics/prevention & control/therapy
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  • 81
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 6;456(7218):2. doi: 10.1038/456002a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987684" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Genetically Modified ; Biotechnology/legislation & jurisprudence ; Food, Genetically Modified/standards ; *Guidelines as Topic ; Humans ; *Legislation, Drug ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 82
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conti, Fiorenzo -- Corbellini, Gilberto -- England -- Nature. 2008 Feb 7;451(7179):627. doi: 10.1038/451627b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256642" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Enhancement/ethics ; Humans ; Italy ; Neurosciences/*ethics ; Persuasive Communication ; *Research Personnel ; *Societies, Scientific ; *Surveys and Questionnaires
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  • 83
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Basu, Paroma -- Qiu, Jane -- Powell, Kendall -- England -- Nature. 2008 Oct 16;455(7215):1002-3. doi: 10.1038/nj7215-1002a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18938259" target="_blank"〉PubMed〈/a〉
    Keywords: Bottle Feeding/statistics & numerical data ; Breast Feeding/statistics & numerical data ; China ; Environmental Pollution/analysis ; Female ; Humans ; India/epidemiology ; *Organizations/organization & administration/statistics & numerical data ; *Research/manpower ; *Research Personnel ; Reward
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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-16
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645842/" 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/PMC3645842/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geschwind, Daniel H -- P50 HD055784/HD/NICHD NIH HHS/ -- R01 MH081754/MH/NIMH NIH HHS/ -- England -- Nature. 2008 Aug 14;454(7206):838-9. doi: 10.1038/454838a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18704077" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/*genetics ; Consanguinity ; *Genetic Predisposition to Disease ; Humans ; Membrane Proteins/genetics ; Mutation
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  • 85
    Publication Date: 2008-11-21
    Description: Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation. Here we identify nucleases from Saccharomyces cerevisiae and human cells that promote Holliday junction resolution, in a manner analogous to that shown by the Escherichia coli Holliday junction resolvase RuvC. The human Holliday junction resolvase, GEN1, and its yeast orthologue, Yen1, were independently identified using two distinct experimental approaches: GEN1 was identified by mass spectrometry following extensive fractionation of HeLa cell-free extracts, whereas Yen1 was detected by screening a yeast gene fusion library for nucleases capable of Holliday junction resolution. The eukaryotic Holliday junction resolvases represent a new subclass of the Rad2/XPG family of nucleases. Recombinant GEN1 and Yen1 resolve Holliday junctions by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ip, Stephen C Y -- Rass, Ulrich -- Blanco, Miguel G -- Flynn, Helen R -- Skehel, J Mark -- West, Stephen C -- Cancer Research UK/United Kingdom -- England -- Nature. 2008 Nov 20;456(7220):357-61. doi: 10.1038/nature07470.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetic Recombination Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020614" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/chemistry/metabolism ; DNA Repair ; HeLa Cells ; Holliday Junction Resolvases/chemistry/genetics/*isolation & ; purification/*metabolism ; Humans ; Recombination, Genetic ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Substrate Specificity
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  • 86
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    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 6;456(7218):2. doi: 10.1038/456002b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987683" target="_blank"〉PubMed〈/a〉
    Keywords: *Human Rights ; Humans ; *Research Personnel
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  • 87
    Publication Date: 2008-11-07
    Description: Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716080/" 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/PMC2716080/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Jun -- Wang, Wei -- Li, Ruiqiang -- Li, Yingrui -- Tian, Geng -- Goodman, Laurie -- Fan, Wei -- Zhang, Junqing -- Li, Jun -- Zhang, Juanbin -- Guo, Yiran -- Feng, Binxiao -- Li, Heng -- Lu, Yao -- Fang, Xiaodong -- Liang, Huiqing -- Du, Zhenglin -- Li, Dong -- Zhao, Yiqing -- Hu, Yujie -- Yang, Zhenzhen -- Zheng, Hancheng -- Hellmann, Ines -- Inouye, Michael -- Pool, John -- Yi, Xin -- Zhao, Jing -- Duan, Jinjie -- Zhou, Yan -- Qin, Junjie -- Ma, Lijia -- Li, Guoqing -- Yang, Zhentao -- Zhang, Guojie -- Yang, Bin -- Yu, Chang -- Liang, Fang -- Li, Wenjie -- Li, Shaochuan -- Li, Dawei -- Ni, Peixiang -- Ruan, Jue -- Li, Qibin -- Zhu, Hongmei -- Liu, Dongyuan -- Lu, Zhike -- Li, Ning -- Guo, Guangwu -- Zhang, Jianguo -- Ye, Jia -- Fang, Lin -- Hao, Qin -- Chen, Quan -- Liang, Yu -- Su, Yeyang -- San, A -- Ping, Cuo -- Yang, Shuang -- Chen, Fang -- Li, Li -- Zhou, Ke -- Zheng, Hongkun -- Ren, Yuanyuan -- Yang, Ling -- Gao, Yang -- Yang, Guohua -- Li, Zhuo -- Feng, Xiaoli -- Kristiansen, Karsten -- Wong, Gane Ka-Shu -- Nielsen, Rasmus -- Durbin, Richard -- Bolund, Lars -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- 077192/Wellcome Trust/United Kingdom -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-04/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Nov 6;456(7218):60-5. doi: 10.1038/nature07484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beijing Genomics Institute at Shenzhen, Shenzhen 518000, China. wangj@genomics.org.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987735" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Asian Continental Ancestry Group/*genetics ; Consensus Sequence ; Databases, Genetic ; *Diploidy ; Genetic Predisposition to Disease/genetics ; Genome, Human/*genetics ; *Genomics ; Haplotypes/genetics ; Humans ; Internet ; Pan troglodytes/genetics ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Sensitivity and Specificity ; Sequence Alignment
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  • 88
    Publication Date: 2008-02-22
    Description: Thrombosis--localized clotting of the blood--can occur in the arterial or the venous circulation and has a major medical impact. Acute arterial thrombosis is the proximal cause of most cases of myocardial infarction (heart attack) and of about 80% of strokes, collectively the most common cause of death in the developed world. Venous thromboembolism is the third leading cause of cardiovascular-associated death. The pathogenic changes that occur in the blood vessel wall and in the blood itself resulting in thrombosis are not fully understood. Understanding these processes is crucial for developing safer and more effective antithrombotic drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848509/" 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/PMC2848509/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mackman, Nigel -- R01 HL095096/HL/NHLBI NIH HHS/ -- R01 HL095096-01/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 Feb 21;451(7181):914-8. doi: 10.1038/nature06797.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA. nmackman@med.unc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288180" target="_blank"〉PubMed〈/a〉
    Keywords: Anticoagulants/pharmacology ; Atherosclerosis/complications/pathology ; Drug-Eluting Stents ; Humans ; Platelet Aggregation Inhibitors/pharmacology ; Thrombosis/complications/*metabolism/pathology/*therapy ; Venous Thrombosis/complications/pathology/therapy
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  • 89
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Nov 6;456(7218):1. doi: 10.1038/456001a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987682" target="_blank"〉PubMed〈/a〉
    Keywords: China/ethnology ; Genetic Counseling/trends ; Genetic Privacy/*legislation & jurisprudence ; *Genome, Human ; Genomics/*legislation & jurisprudence/trends ; Humans ; Individuality ; Male ; Nigeria/ethnology ; Pharmacogenetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 90
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sloboda, John -- England -- Nature. 2008 Jul 3;454(7200):32-3. doi: 10.1038/454032a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Law, Politics and Justice, Keele University, Newcastle, Staffordshire ST5 5BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596790" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Culture ; Female ; Humans ; Music/*psychology ; Research/trends ; *Science
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 91
    Publication Date: 2008-10-17
    Description: Neuropsychiatric conditions such as autism and schizophrenia have long been attributed to genetic alterations, but identifying the genes responsible has proved challenging. Microarray experiments have now revealed abundant copy-number variation--a type of variation in which stretches of DNA are duplicated, deleted and sometimes rearranged--in the human population. Genes affected by copy-number variation are good candidates for research into disease susceptibility. The complexity of neuropsychiatric genetics, however, dictates that assessment of the biomedical relevance of copy-number variants and the genes that they affect needs to be considered in an integrated context.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, Edwin H Jr -- Scherer, Stephen W -- HD055751/HD/NICHD NIH HHS/ -- England -- Nature. 2008 Oct 16;455(7215):919-23. doi: 10.1038/nature07458.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Juvenile Research, Department of Psychiatry, University of Illinois, 1747 West Roosevelt Road, Chicago, Illinois 60608, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923514" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics ; Gene Dosage/*genetics ; Genetic Predisposition to Disease/genetics ; Genomics ; Humans ; Mental Disorders/*genetics ; Nervous System Diseases/*genetics ; Schizophrenia/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 92
    Publication Date: 2008-11-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bayry, Jagadeesh -- England -- Nature. 2008 Nov 20;456(7220):285. doi: 10.1038/456285e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Paris.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/genetics/immunology/*metabolism ; Autoimmune Diseases/genetics/immunology ; CTLA-4 Antigen ; Dendritic Cells/immunology ; Humans ; Immune Tolerance/*immunology ; Mice ; Neoplasms/drug therapy/immunology ; T-Lymphocytes, Regulatory/*immunology/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 93
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gewin, Virginia -- England -- Nature. 2008 Mar 27;452(7186):498-500. doi: 10.1038/nj7186-498a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18444262" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Allergy and Immunology/education/manpower ; Biotechnology/education/manpower/*trends ; *Drug Design ; Drug Industry/education/manpower/*trends ; Humans ; Internationality ; Vaccines/economics/*immunology
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  • 94
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smaglik, Paul -- England -- Nature. 2008 Jun 5;453(7196):818-20. doi: 10.1038/nj7196-818a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18623624" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*organization & administration/trends ; Alabama ; Biomedical Research/trends ; Biotechnology/*manpower/*organization & administration/trends ; Employment/trends ; Entrepreneurship/trends ; Humans ; United States ; United States National Aeronautics and Space Administration/*trends ; Universities/manpower
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  • 95
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-31
    Description: An experiment by the Gates Foundation is food for thought for other research agencies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Oct 30;455(7217):1150. doi: 10.1038/4551150a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971970" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics ; Creativity ; Foundations/*economics ; Humans ; Investments ; National Institutes of Health (U.S.)/economics ; Peer Review, Research/*standards ; Research Support as Topic/*economics ; *Risk-Taking ; United States
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  • 96
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    Nature Publishing Group (NPG)
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bazan, Gene -- England -- Nature. 2008 Nov 6;456(7218):30. doi: 10.1038/456030a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987718" target="_blank"〉PubMed〈/a〉
    Keywords: *Bioelectric Energy Sources/economics/trends ; Conservation of Energy Resources/economics/*methods ; Cost-Benefit Analysis ; Ecosystem ; *Feces ; Humans ; *Power Plants ; Soil
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  • 97
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smaglik, Paul -- England -- Nature. 2008 Mar 20;452(7185):382-3. doi: 10.1038/nj7185-382a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18409208" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*manpower ; Continental Population Groups/genetics/statistics & numerical data ; Environment ; Humans ; Minority Groups/*statistics & numerical data ; Personnel Selection ; Philippines/ethnology ; Physician-Patient Relations ; *Prejudice ; Public Health/*statistics & numerical data ; Research Personnel/*statistics & numerical data ; United States/epidemiology ; Wounds, Gunshot/epidemiology
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  • 98
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, Nicholas -- England -- Nature. 2008 Jun 26;453(7199):1186-7. doi: 10.1038/4531186a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉AHRC Research Centre for the History and Analysis of Recorded Music, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18580933" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Humans ; Music/*psychology ; Time Factors
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  • 99
    Publication Date: 2008-07-11
    Description: Polo-like kinase-1 (PLK1) is an essential mitotic kinase regulating multiple aspects of the cell division process. Activation of PLK1 requires phosphorylation of a conserved threonine residue (Thr 210) in the T-loop of the PLK1 kinase domain, but the kinase responsible for this has not yet been affirmatively identified. Here we show that in human cells PLK1 activation occurs several hours before entry into mitosis, and requires aurora A (AURKA, also known as STK6)-dependent phosphorylation of Thr 210. We find that aurora A can directly phosphorylate PLK1 on Thr 210, and that activity of aurora A towards PLK1 is greatly enhanced by Bora (also known as C13orf34 and FLJ22624), a known cofactor for aurora A (ref. 7). We show that Bora/aurora-A-dependent phosphorylation is a prerequisite for PLK1 to promote mitotic entry after a checkpoint-dependent arrest. Importantly, expression of a PLK1-T210D phospho-mimicking mutant partially overcomes the requirement for aurora A in checkpoint recovery. Taken together, these data demonstrate that the initial activation of PLK1 is a primary function of aurora A.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macurek, Libor -- Lindqvist, Arne -- Lim, Dan -- Lampson, Michael A -- Klompmaker, Rob -- Freire, Raimundo -- Clouin, Christophe -- Taylor, Stephen S -- Yaffe, Michael B -- Medema, Rene H -- CA112967/CA/NCI NIH HHS/ -- GM-60594/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Sep 4;455(7209):119-23. doi: 10.1038/nature07185. Epub 2008 Jul 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, University Medical Center Utrecht, Utrecht 3584CG, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615013" target="_blank"〉PubMed〈/a〉
    Keywords: Aurora Kinase A ; Aurora Kinases ; Cell Cycle/*physiology ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; DNA Damage ; Enzyme Activation ; Humans ; Mitosis ; Molecular Sequence Data ; Phosphorylation ; Phosphothreonine/metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Time Factors
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  • 100
    Publication Date: 2008-05-30
    Description: With the recent recognition of non-coding RNAs (ncRNAs) flanking many genes, a central issue is to obtain a full understanding of their potential roles in regulated gene transcription programmes, possibly through different mechanisms. Here we show that an RNA-binding protein, TLS (for translocated in liposarcoma), serves as a key transcriptional regulatory sensor of DNA damage signals that, on the basis of its allosteric modulation by RNA, specifically binds to and inhibits CREB-binding protein (CBP) and p300 histone acetyltransferase activities on a repressed gene target, cyclin D1 (CCND1) in human cell lines. Recruitment of TLS to the CCND1 promoter to cause gene-specific repression is directed by single-stranded, low-copy-number ncRNA transcripts tethered to the 5' regulatory regions of CCND1 that are induced in response to DNA damage signals. Our data suggest that signal-induced ncRNAs localized to regulatory regions of transcription units can act cooperatively as selective ligands, recruiting and modulating the activities of distinct classes of RNA-binding co-regulators in response to specific signals, providing an unexpected ncRNA/RNA-binding protein-based strategy to integrate transcriptional programmes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823488/" 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/PMC2823488/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiangting -- Arai, Shigeki -- Song, Xiaoyuan -- Reichart, Donna -- Du, Kun -- Pascual, Gabriel -- Tempst, Paul -- Rosenfeld, Michael G -- Glass, Christopher K -- Kurokawa, Riki -- CA097134/CA/NCI NIH HHS/ -- CA52599/CA/NCI NIH HHS/ -- DK074868/DK/NIDDK NIH HHS/ -- DK39949/DK/NIDDK NIH HHS/ -- HL59694/HL/NHLBI NIH HHS/ -- NS34934/NS/NINDS NIH HHS/ -- P30 CA08748/CA/NCI NIH HHS/ -- R01 CA052599/CA/NCI NIH HHS/ -- R01 CA052599-19/CA/NCI NIH HHS/ -- R01 DK091183/DK/NIDDK NIH HHS/ -- R01 HL059694/HL/NHLBI NIH HHS/ -- R01 HL059694-10/HL/NHLBI NIH HHS/ -- R01 NS034934/NS/NINDS NIH HHS/ -- R01 NS034934-20A1/NS/NINDS NIH HHS/ -- R37 DK039949/DK/NIDDK NIH HHS/ -- R37 DK039949-26/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jul 3;454(7200):126-30. doi: 10.1038/nature06992. Epub 2008 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509338" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; CREB-Binding Protein/antagonists & inhibitors/metabolism ; Cell Line ; Consensus Sequence ; Cyclin D1/genetics ; DNA Damage ; *Down-Regulation ; HeLa Cells ; Histone Acetyltransferases/antagonists & inhibitors/metabolism ; Humans ; Oligonucleotides/genetics ; Promoter Regions, Genetic/genetics ; RNA, Untranslated/genetics/*metabolism ; RNA-Binding Protein FUS/genetics/*metabolism ; *Transcription, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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