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  • 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
    Electronic Resource
    Electronic Resource
    Springer
    Environmental management 8 (1984), S. 309-324 
    ISSN: 1432-1009
    Keywords: Animals ; Indicators ; Air pollution ; Ecosystem responses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract With existing and proposed air-quality regulations, ecological disasters resulting from air emissions such as those observed at Copperhill, Tennessee, and Sudbury, Ontario, are unlikely. Current air-quality standards, however, may not protect ecosystems from subacute and chronic exposure to air emissions. The encouragement of the use of coal for energy production and the development of the fossil-fuel industries, including oil shales, tar sands, and coal liquification, point to an increase and spread of fossil-fuel emissions and the potential to influence a number of natural ecosystems. This paper reviews the reported responses of ecosystems to air-borne pollutants and discusses the use of animals as indicators of ecosystem responses to these pollutants. Animal species and populations can act as important indicators of biotic and abiotic responses of aquatic and terrestrial ecosystems. These responses can indicate long-term trends in ecosystem health and productivity, chemical cycling, genetics, and regulation. For short-term trends, fish and wildlife also serve as monitors of changes in community structure, signaling food-web contamination, as well as providing a measure of ecosystem vitality. Information is presented to show not only the importance of animals as indicators of ecosystem responses to air-quality degradation, but also their value as air-pollution indices, that is, as air-quality-related values (AQRV), required in current air-pollution regulation.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2009-12-18
    Description: Avian brood parasites and their hosts provide model systems for investigating links between recognition, learning, and their fitness consequences. One major evolutionary puzzle has continued to capture the attention of naturalists for centuries: why do hosts of brood parasites generally fail to recognize parasitic offspring after they have hatched from the egg, even when the host and parasitic chicks differ to almost comic degrees? One prominent theory to explain this pattern proposes that the costs of mistakenly learning to recognize the wrong offspring make recognition maladaptive. Here we show that American coots, Fulica americana, can recognize and reject parasitic chicks in their brood by using learned cues, despite the fact that the hosts and the brood parasites are of the same species. A series of chick cross-fostering experiments confirm that coots use first-hatched chicks in a brood as referents to learn to recognize their own chicks and then discriminate against later-hatched parasitic chicks in the same brood. When experimentally provided with the wrong reference chicks, coots can be induced to discriminate against their own offspring, confirming that the learning errors proposed by theory can exist. However, learning based on hatching order is reliable in naturally parasitized coot nests because host eggs hatch predictably ahead of parasite eggs. Conversely, a lack of reliable information may help to explain why the evolution of chick recognition is not more common in hosts of most interspecific brood parasites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shizuka, Daizaburo -- Lyon, Bruce E -- England -- Nature. 2010 Jan 14;463(7278):223-6. doi: 10.1038/nature08655. Epub 2009 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, California 95064, USA. shizuka@biology.ucsc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016486" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/*parasitology/*physiology ; British Columbia ; Cues ; Discrimination Learning/*physiology ; Feeding Behavior/physiology ; Genetic Fitness ; Nesting Behavior/*physiology ; Ovum/growth & development ; Pattern Recognition, Visual/physiology ; Survival Rate ; Time Factors ; Wetlands
    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: 2009-10-09
    Description: Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Donald F -- Pinto, Dalila -- Redon, Richard -- Feuk, Lars -- Gokcumen, Omer -- Zhang, Yujun -- Aerts, Jan -- Andrews, T Daniel -- Barnes, Chris -- Campbell, Peter -- Fitzgerald, Tomas -- Hu, Min -- Ihm, Chun Hwa -- Kristiansson, Kati -- Macarthur, Daniel G -- Macdonald, Jeffrey R -- Onyiah, Ifejinelo -- Pang, Andy Wing Chun -- Robson, Sam -- Stirrups, Kathy -- Valsesia, Armand -- Walter, Klaudia -- Wei, John -- Wellcome Trust Case Control Consortium -- Tyler-Smith, Chris -- Carter, Nigel P -- Lee, Charles -- Scherer, Stephen W -- Hurles, Matthew E -- 077006/Z/05/Z/Wellcome Trust/United Kingdom -- 077008/Wellcome Trust/United Kingdom -- 077009/Wellcome Trust/United Kingdom -- 077014/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- GM081533/GM/NIGMS NIH HHS/ -- HG004221/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Apr 1;464(7289):704-12. doi: 10.1038/nature08516. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812545" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/genetics ; DNA Copy Number Variations/*genetics ; Gene Duplication ; Genetic Predisposition to Disease/*genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genotype ; Haplotypes/genetics ; Humans ; Mutagenesis/*genetics ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; Reproducibility of Results
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    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
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  • 6
    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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  • 7
    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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  • 8
    Publication Date: 2009-12-17
    Description: The Red Queen describes a view of nature in which species continually evolve but do not become better adapted. It is one of the more distinctive metaphors of evolutionary biology, but no test of its claim that speciation occurs at a constant rate has ever been made against competing models that can predict virtually identical outcomes, nor has any mechanism been proposed that could cause the constant-rate phenomenon. Here we use 101 phylogenies of animal, plant and fungal taxa to test the constant-rate claim against four competing models. Phylogenetic branch lengths record the amount of time or evolutionary change between successive events of speciation. The models predict the distribution of these lengths by specifying how factors combine to bring about speciation, or by describing how rates of speciation vary throughout a tree. We find that the hypotheses that speciation follows the accumulation of many small events that act either multiplicatively or additively found support in 8% and none of the trees, respectively. A further 8% of trees hinted that the probability of speciation changes according to the amount of divergence from the ancestral species, and 6% suggested speciation rates vary among taxa. By comparison, 78% of the trees fit the simplest model in which new species emerge from single events, each rare but individually sufficient to cause speciation. This model predicts a constant rate of speciation, and provides a new interpretation of the Red Queen: the metaphor of species losing a race against a deteriorating environment is replaced by a view linking speciation to rare stochastic events that cause reproductive isolation. Attempts to understand species-radiations or why some groups have more or fewer species should look to the size of the catalogue of potential causes of speciation shared by a group of closely related organisms rather than to how those causes combine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venditti, Chris -- Meade, Andrew -- Pagel, Mark -- England -- Nature. 2010 Jan 21;463(7279):349-52. doi: 10.1038/nature08630. Epub 2009 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Reading, Reading, Berkshire, RG6 6BX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010607" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; *Genetic Speciation ; *Models, Biological ; *Phylogeny ; Selection, Genetic ; Stochastic Processes
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  • 9
    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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  • 10
    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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  • 11
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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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  • 12
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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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  • 13
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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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  • 14
    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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  • 15
    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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  • 16
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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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  • 17
    Publication Date: 2008-05-30
    Description: As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments. Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate (H(13)CO(3)(-)) and (13)CO(2) following intravenous injection of hyperpolarized H(13)CO(3)(-). The technique was demonstrated in a mouse tumour model, which showed that the average tumour interstitial pH was significantly lower than the surrounding tissue. Given that bicarbonate is an endogenous molecule that can be infused in relatively high concentrations into patients, we propose that this technique could be used clinically to image pathological processes that are associated with alterations in tissue pH, such as cancer, ischaemia and inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallagher, Ferdia A -- Kettunen, Mikko I -- Day, Sam E -- Hu, De-En -- Ardenkjaer-Larsen, Jan Henrik -- Zandt, Rene in 't -- Jensen, Pernille R -- Karlsson, Magnus -- Golman, Klaes -- Lerche, Mathilde H -- Brindle, Kevin M -- C197/A3514/Cancer Research UK/United Kingdom -- England -- Nature. 2008 Jun 12;453(7197):940-3. doi: 10.1038/nature07017. Epub 2008 May 28.〈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/18509335" target="_blank"〉PubMed〈/a〉
    Keywords: Acid-Base Equilibrium ; Animals ; Bicarbonates/*metabolism ; Carbon Dioxide/metabolism ; Carbon Isotopes ; Carbonic Anhydrases/metabolism ; Catalysis ; Hydrogen-Ion Concentration ; Lymphoma/*diagnosis/*metabolism/pathology ; Magnetic Resonance Imaging/*methods ; Mice ; Neoplasm Transplantation ; Phantoms, Imaging
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  • 18
    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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  • 19
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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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  • 20
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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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  • 21
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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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  • 22
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    Publication Date: 2008-01-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pera, Martin F -- England -- Nature. 2008 Jan 10;451(7175):135-6. doi: 10.1038/451135a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18185576" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Differentiation ; Embryonic Stem Cells/*cytology/metabolism ; Fetus/cytology ; Fibroblasts/cytology ; HMGB Proteins/genetics/metabolism ; Humans ; Kruppel-Like Transcription Factors/genetics/metabolism ; Mice ; Octamer Transcription Factor-3/genetics/metabolism ; Pluripotent Stem Cells/*cytology/*metabolism ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; SOXB1 Transcription Factors ; Transcription Factors/genetics/metabolism
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  • 23
    Publication Date: 2008-05-30
    Description: The extinct placoderm fishes were the dominant group of vertebrates throughout the Middle Palaeozoic era, yet controversy about their relationships within the gnathostomes (jawed vertebrates) is partly due to different interpretations of their reproductive biology. Here we document the oldest record of a live-bearing vertebrate in a new ptyctodontid placoderm, Materpiscis attenboroughi gen. et sp. nov., from the Late Devonian Gogo Formation of Australia (approximately 380 million years ago). The new specimen, remarkably preserved in three dimensions, contains a single, intra-uterine embryo connected by a permineralized umbilical cord. An amorphous crystalline mass near the umbilical cord possibly represents the recrystallized yolk sac. Another ptyctodont from the Gogo Formation, Austroptyctodus gardineri, also shows three small embryos inside it in the same position. Ptyctodontids have already provided the oldest definite evidence for vertebrate copulation, and the new specimens confirm that some placoderms had a remarkably advanced reproductive biology, comparable to that of some modern sharks and rays. The new discovery points to internal fertilization and viviparity in vertebrates as originating earliest within placoderms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, John A -- Trinajstic, Kate -- Young, Gavin C -- Senden, Tim -- England -- Nature. 2008 May 29;453(7195):650-2. doi: 10.1038/nature06966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Museum Victoria, Melbourne, PO Box 666, Melbourne 3001, Australia. jlong@museum.vic.gov.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509443" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; Biological Evolution ; Female ; Fishes/classification/*embryology/*physiology ; *Fossils ; History, Ancient ; Microscopy, Electron, Scanning ; Viviparity, Nonmammalian/*physiology
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  • 24
    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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  • 25
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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):826-7. doi: 10.1038/456826a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19079062" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/physiology ; *Carrier Proteins/metabolism/radiation effects ; Cells/*cytology ; Halorhodopsins ; Ion Channels/physiology ; *Light ; Retinaldehyde/metabolism
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  • 26
    Publication Date: 2008-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christian, Max -- Finer, Matt -- Ross, Carl -- England -- Nature. 2008 Oct 16;455(7215):861. doi: 10.1038/455861c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923487" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Carbon Dioxide/analysis ; Conservation of Natural Resources/*economics/methods/*trends ; Ecuador ; Fuel Oils/*economics ; *Greenhouse Effect ; *International Cooperation
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  • 27
    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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  • 28
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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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  • 29
    Publication Date: 2008-09-12
    Description: Cell growth and proliferation require coordinated ribosomal biogenesis and translation. Eukaryotic initiation factors (eIFs) control translation at the rate-limiting step of initiation. So far, only two eIFs connect extracellular stimuli to global translation rates: eIF4E acts in the eIF4F complex and regulates binding of capped messenger RNA to 40S subunits, downstream of growth factors, and eIF2 controls loading of the ternary complex on the 40S subunit and is inhibited on stress stimuli. No eIFs have been found to link extracellular stimuli to the activity of the large 60S ribosomal subunit. eIF6 binds 60S ribosomes precluding ribosome joining in vitro. However, studies in yeasts showed that eIF6 is required for ribosome biogenesis rather than translation. Here we show that mammalian eIF6 is required for efficient initiation of translation, in vivo. eIF6 null embryos are lethal at preimplantation. Heterozygous mice have 50% reduction of eIF6 levels in all tissues, and show reduced mass of hepatic and adipose tissues due to a lower number of cells and to impaired G1/S cell cycle progression. eIF6(+/-) cells retain sufficient nucleolar eIF6 and normal ribosome biogenesis. The liver of eIF6(+/-) mice displays an increase of 80S in polysomal profiles, indicating a defect in initiation of translation. Consistently, isolated hepatocytes have impaired insulin-stimulated translation. Heterozygous mouse embryonic fibroblasts recapitulate the organism phenotype and have normal ribosome biogenesis, reduced insulin-stimulated translation, and delayed G1/S phase progression. Furthermore, eIF6(+/-) cells are resistant to oncogene-induced transformation. Thus, eIF6 is the first eIF associated with the large 60S subunit that regulates translation in response to extracellular signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753212/" 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/PMC2753212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gandin, Valentina -- Miluzio, Annarita -- Barbieri, Anna Maria -- Beugnet, Anne -- Kiyokawa, Hiroaki -- Marchisio, Pier Carlo -- Biffo, Stefano -- GGP05043/Telethon/Italy -- R01/PHS HHS/ -- R01 CA112282/CA/NCI NIH HHS/ -- R01 CA112282-04/CA/NCI NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):684-8. doi: 10.1038/nature07267. Epub 2008 Sep 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Histology and Cell Growth Laboratory, San Raffaele Science Institute, Via Olgettina 58, 20132 Milan, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18784653" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/cytology ; Animals ; Body Weight ; Cell Division/drug effects ; Cell Nucleolus/metabolism ; *Cell Transformation, Neoplastic ; Cells, Cultured ; Cytoplasm/metabolism ; Fibroblasts ; G1 Phase/drug effects ; Heterozygote ; Insulin/pharmacology ; Liver/cytology/growth & development ; Mice ; NIH 3T3 Cells ; Oncogenes/genetics ; *Peptide Chain Initiation, Translational/drug effects ; Peptide Initiation Factors/deficiency/genetics/*metabolism ; Ribosomes/chemistry/metabolism ; *S Phase/drug effects
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  • 30
    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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  • 31
    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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  • 32
    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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  • 33
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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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  • 34
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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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  • 35
    Publication Date: 2007
    Description: Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425380/" 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/PMC3425380/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huber, Daniel -- Petreanu, Leopoldo -- Ghitani, Nima -- Ranade, Sachin -- Hromadka, Tomas -- Mainen, Zach -- Svoboda, Karel -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Jan 3;451(7174):61-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18094685" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology/radiation effects ; Algal Proteins/genetics/metabolism ; Animals ; Behavior, Animal/*physiology/*radiation effects ; Cerebral Cortex/cytology/*physiology/*radiation effects ; Electric Stimulation ; Learning/*physiology/radiation effects ; Mice ; Movement/*physiology ; Optics and Photonics ; Photic Stimulation ; Pyramidal Cells/metabolism/radiation effects ; Rhodopsins, Microbial/genetics/metabolism
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  • 36
    Publication Date: 2008-03-28
    Description: Although information storage in the central nervous system is thought to be primarily mediated by various forms of synaptic plasticity, other mechanisms, such as modifications in membrane excitability, are available. Local dendritic spikes are nonlinear voltage events that are initiated within dendritic branches by spatially clustered and temporally synchronous synaptic input. That local spikes selectively respond only to appropriately correlated input allows them to function as input feature detectors and potentially as powerful information storage mechanisms. However, it is currently unknown whether any effective form of local dendritic spike plasticity exists. Here we show that the coupling between local dendritic spikes and the soma of rat hippocampal CA1 pyramidal neurons can be modified in a branch-specific manner through an N-methyl-d-aspartate receptor (NMDAR)-dependent regulation of dendritic Kv4.2 potassium channels. These data suggest that compartmentalized changes in branch excitability could store multiple complex features of synaptic input, such as their spatio-temporal correlation. We propose that this 'branch strength potentiation' represents a previously unknown form of information storage that is distinct from that produced by changes in synaptic efficacy both at the mechanistic level and in the type of information stored.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Losonczy, Attila -- Makara, Judit K -- Magee, Jeffrey C -- England -- Nature. 2008 Mar 27;452(7186):436-41. doi: 10.1038/nature06725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Dr Ashburn, Virginia 20147, USA. losonczya@janelia.hhmi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368112" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology ; Animals ; Cell Shape ; Dendrites/*physiology ; Ion Channel Gating ; Male ; Mice ; Models, Neurological ; Neuronal Plasticity/*physiology ; Pyramidal Cells/*cytology/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Shal Potassium Channels/deficiency/genetics/metabolism
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  • 37
    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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  • 38
    Publication Date: 2008-11-14
    Description: Many complex behaviours, like speech or music, have a hierarchical organization with structure on many timescales, but it is not known how the brain controls the timing of behavioural sequences, or whether different circuits control different timescales of the behaviour. Here we address these issues by using temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We find that cooling the premotor nucleus HVC (formerly known as the high vocal centre) slows song speed across all timescales by up to 45 per cent but only slightly alters the acoustic structure, whereas cooling the downstream motor nucleus RA (robust nucleus of the arcopallium) has no observable effect on song timing. Our observations suggest that dynamics within HVC are involved in the control of song timing, perhaps through a chain-like organization. Local manipulation of brain temperature should be broadly applicable to the identification of neural circuitry that controls the timing of behavioural sequences and, more generally, to the study of the origin and role of oscillatory and other forms of brain dynamics in neural systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723166/" 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/PMC2723166/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Michael A -- Fee, Michale S -- DC009280/DC/NIDCD NIH HHS/ -- K99 DC009280/DC/NIDCD NIH HHS/ -- K99 DC009280-02/DC/NIDCD NIH HHS/ -- MH067105/MH/NIMH NIH HHS/ -- R01 MH067105/MH/NIMH NIH HHS/ -- R01 MH067105-04/MH/NIMH NIH HHS/ -- England -- Nature. 2008 Nov 13;456(7219):189-94. doi: 10.1038/nature07448.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, 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/19005546" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cold Temperature ; Efferent Pathways/physiology ; Finches/*physiology ; High Vocal Center/*physiology ; Neurons/physiology ; Prosencephalon/*physiology/radiography ; Time Factors ; Vocalization, Animal/*physiology
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  • 39
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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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  • 40
    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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  • 41
    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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  • 42
    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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  • 43
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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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  • 44
    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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  • 45
    Publication Date: 2008-04-18
    Description: We often face alternatives that we are free to choose between. Planning movements to select an alternative involves several areas in frontal and parietal cortex that are anatomically connected into long-range circuits. These areas must coordinate their activity to select a common movement goal, but how neural circuits make decisions remains poorly understood. Here we simultaneously record from the dorsal premotor area (PMd) in frontal cortex and the parietal reach region (PRR) in parietal cortex to investigate neural circuit mechanisms for decision making. We find that correlations in spike and local field potential (LFP) activity between these areas are greater when monkeys are freely making choices than when they are following instructions. We propose that a decision circuit featuring a sub-population of cells in frontal and parietal cortex may exchange information to coordinate activity between these areas. Cells participating in this decision circuit may influence movement choices by providing a common bias to the selection of movement goals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728060/" 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/PMC2728060/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pesaran, Bijan -- Nelson, Matthew J -- Andersen, Richard A -- R01 EY007492/EY/NEI NIH HHS/ -- R01 EY007492-19/EY/NEI NIH HHS/ -- England -- Nature. 2008 May 15;453(7193):406-9. doi: 10.1038/nature06849. Epub 2008 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neural Science, New York University, New York, New York 10003, USA. bijan@nyu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18418380" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/physiology ; Animals ; Choice Behavior/*physiology ; Fixation, Ocular/physiology ; Frontal Lobe/*physiology ; Macaca mulatta/*physiology ; Male ; Neural Pathways/*physiology ; Neurons/metabolism ; Parietal Lobe/*physiology ; Photic Stimulation ; Probability ; ROC Curve ; Reward ; Saccades/physiology
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  • 46
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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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  • 47
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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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  • 48
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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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  • 49
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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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  • 50
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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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  • 51
    Publication Date: 2008-08-15
    Description: Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins. It is induced in activated T cells and is reported to process a variety of substrates including the anti-inflammatory cytokine transforming growth factor (TGF)-beta1 (refs 2-4), but the non-redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T-cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta1. Furin-deficient T regulatory (Treg) cells were less protective in a T-cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin-deficient effector cells were inherently over-active and were resistant to suppressive activity of wild-type Treg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non-redundant, essential function in regulating TGF-beta1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2758057/" 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/PMC2758057/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pesu, Marko -- Watford, Wendy T -- Wei, Lai -- Xu, Lili -- Fuss, Ivan -- Strober, Warren -- Andersson, John -- Shevach, Ethan M -- Quezado, Martha -- Bouladoux, Nicolas -- Roebroek, Anton -- Belkaid, Yasmine -- Creemers, John -- O'Shea, John J -- Z99 EY999999/Intramural NIH HHS/ -- England -- Nature. 2008 Sep 11;455(7210):246-50. doi: 10.1038/nature07210.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. pesum@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18701887" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/immunology ; Antigens, CD4/immunology/metabolism ; Autoimmunity/immunology ; Colitis/immunology ; Furin/deficiency/genetics/*metabolism ; Gene Expression Profiling ; Immune Tolerance/*immunology ; Immunologic Memory/immunology ; Integrin alpha Chains/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes/cytology/*enzymology/*immunology ; Thymus Gland/cytology/immunology ; Transforming Growth Factor beta1/biosynthesis/genetics/immunology
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  • 52
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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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  • 53
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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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  • 54
    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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  • 55
    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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  • 56
    Publication Date: 2008-03-28
    Description: As perceived by Darwin, evolutionary adaptation by the processes of mutation and selection is difficult to understand for complex features that are the product of numerous traits acting in concert, for example the eye or the apparatus of flight. Typically, mutations simultaneously affect multiple phenotypic characters. This phenomenon is known as pleiotropy. The impact of pleiotropy on evolution has for decades been the subject of formal analysis. Some authors have suggested that pleiotropy can impede evolutionary progress (a so-called 'cost of complexity'). The plausibility of various phenomena attributed to pleiotropy depends on how many traits are affected by each mutation and on our understanding of the correlation between the number of traits affected by each gene substitution and the size of mutational effects on individual traits. Here we show, by studying pleiotropy in mice with the use of quantitative trait loci (QTLs) affecting skeletal characters, that most QTLs affect a relatively small subset of traits and that a substitution at a QTL has an effect on each trait that increases with the total number of traits affected. This suggests that evolution of higher organisms does not suffer a 'cost of complexity' because most mutations affect few traits and the size of the effects does not decrease with pleiotropy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wagner, Gunter P -- Kenney-Hunt, Jane P -- Pavlicev, Mihaela -- Peck, Joel R -- Waxman, David -- Cheverud, James M -- England -- Nature. 2008 Mar 27;452(7186):470-2. doi: 10.1038/nature06756.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06520-8106, USA. gunter.wagner@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368117" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Body Size/*genetics ; Body Weight/genetics ; Crosses, Genetic ; Female ; Male ; Mice ; Mice, Inbred Strains ; *Models, Genetic ; Mutation/*genetics ; Phenotype ; Quantitative Trait Loci/*genetics ; Selection, Genetic ; *Skeleton
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  • 57
    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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  • 58
    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hunt, Patricia -- England -- Nature. 2008 Jun 19;453(7198):964. doi: 10.1038/453964a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563110" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Laboratory/abnormalities ; Benzalkonium Compounds/*toxicity ; Benzhydryl Compounds ; Disinfectants/chemistry/*toxicity ; Environmental Exposure ; Female ; Fertility/*drug effects ; Fetal Death/chemically induced ; *Housing, Animal ; *Laboratories ; Male ; Mice ; Phenols ; Pregnancy ; Quaternary Ammonium Compounds/*toxicity
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  • 59
    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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  • 60
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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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  • 61
    Publication Date: 2008-08-22
    Description: The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gaspard, Nicolas -- Bouschet, Tristan -- Hourez, Raphael -- Dimidschstein, Jordane -- Naeije, Gilles -- van den Ameele, Jelle -- Espuny-Camacho, Ira -- Herpoel, Adele -- Passante, Lara -- Schiffmann, Serge N -- Gaillard, Afsaneh -- Vanderhaeghen, Pierre -- England -- Nature. 2008 Sep 18;455(7211):351-7. doi: 10.1038/nature07287. Epub 2008 Aug 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IRIBHM (Institute for Interdisciplinary Research), Universite Libre de Bruxelles (ULB).〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18716623" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/drug effects/physiology ; *Cell Differentiation/drug effects ; Cell Lineage/drug effects ; Cerebral Cortex/*cytology/drug effects/*embryology ; Embryonic Stem Cells/*cytology/drug effects ; Mice ; Pyramidal Cells/drug effects ; Veratrum Alkaloids/pharmacology
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  • 62
    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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  • 63
    Publication Date: 2008-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petherick, Anna -- England -- Nature. 2008 Apr 17;452(7189):789. doi: 10.1038/452789a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421322" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Conservation of Natural Resources/*methods ; Madagascar ; Species Specificity
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  • 64
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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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  • 65
    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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  • 66
    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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  • 67
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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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  • 68
    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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  • 69
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gee, Henry -- England -- Nature. 2008 Jun 19;453(7198):999-1000. doi: 10.1038/453999a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563145" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chordata/classification/*genetics ; *Evolution, Molecular ; Genome/*genetics ; Phylogeny ; Vertebrates/classification/genetics
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  • 70
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    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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  • 71
    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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  • 72
    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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  • 73
    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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  • 74
    Publication Date: 2008-11-04
    Description: The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain. Layer-specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis have been identified. However, most of the neuronal cell-surface molecules critical for layer organization are expressed broadly in the developing nervous system, raising the question of how these so-called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc-finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target-layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia-induced axon targeting is mediated through the ubiquitously expressed Cadherin-N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth-order-dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division but also connection diversity of projecting neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petrovic, Milan -- Hummel, Thomas -- England -- Nature. 2008 Dec 11;456(7223):800-3. doi: 10.1038/nature07407. Epub 2008 Nov 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Neurobiologie, Universitat Munster, Badestrasse 9, D-48149 Munster, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18978776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/metabolism/physiology ; Cadherins/metabolism ; Compound Eye, Arthropod/growth & development ; DNA-Binding Proteins/genetics/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/genetics/*growth & development/*metabolism ; Gene Expression Regulation, Developmental ; Nerve Tissue Proteins/genetics/metabolism ; Photoreceptor Cells, Invertebrate/metabolism/physiology ; Protein Transport ; Time Factors
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  • 75
    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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  • 76
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    Unknown
    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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  • 77
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    Unknown
    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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  • 78
    Publication Date: 2008-07-22
    Description: Although many animals use the Earth's magnetic field for orientation and navigation, the precise biophysical mechanisms underlying magnetic sensing have been elusive. One theoretical model proposes that geomagnetic fields are perceived by chemical reactions involving specialized photoreceptors. However, the specific photoreceptor involved in such magnetoreception has not been demonstrated conclusively in any animal. Here we show that the ultraviolet-A/blue-light photoreceptor cryptochrome (Cry) is necessary for light-dependent magnetosensitive responses in Drosophila melanogaster. In a binary-choice behavioural assay for magnetosensitivity, wild-type flies show significant naive and trained responses to a magnetic field under full-spectrum light ( approximately 300-700 nm) but do not respond to the field when wavelengths in the Cry-sensitive, ultraviolet-A/blue-light part of the spectrum (〈420 nm) are blocked. Notably, Cry-deficient cry(0) and cry(b) flies do not show either naive or trained responses to a magnetic field under full-spectrum light. Moreover, Cry-dependent magnetosensitivity does not require a functioning circadian clock. Our work provides, to our knowledge, the first genetic evidence for a Cry-based magnetosensitive system in any animal.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2559964/" 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/PMC2559964/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gegear, Robert J -- Casselman, Amy -- Waddell, Scott -- Reppert, Steven M -- R01 MH069883/MH/NIMH NIH HHS/ -- R01 MH069883-05/MH/NIMH NIH HHS/ -- R01 NS047141/NS/NINDS NIH HHS/ -- R01 NS047141-05/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Aug 21;454(7207):1014-8. doi: 10.1038/nature07183. Epub 2008 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18641630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology/radiation effects ; Circadian Rhythm/physiology/radiation effects ; Cryptochromes ; Drosophila melanogaster/*physiology/*radiation effects ; Flavoproteins/genetics/*metabolism ; *Light ; *Magnetics ; Mutation ; Sensation/physiology/*radiation effects
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  • 79
    Publication Date: 2008-02-19
    Description: Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences. Recent genomic studies in Arabidopsis thaliana have revealed that many endogenous genes are methylated either within their promoters or within their transcribed regions, and that gene methylation is highly correlated with transcription levels. However, plants have different types of methylation controlled by different genetic pathways, and detailed information on the methylation status of each cytosine in any given genome is lacking. To this end, we generated a map at single-base-pair resolution of methylated cytosines for Arabidopsis, by combining bisulphite treatment of genomic DNA with ultra-high-throughput sequencing using the Illumina 1G Genome Analyser and Solexa sequencing technology. This approach, termed BS-Seq, unlike previous microarray-based methods, allows one to sensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts. Here we describe methylation on previously inaccessible components of the genome and analyse the DNA methylation sequence composition and distribution. We also describe the effect of various DNA methylation mutants on genome-wide methylation patterns, and demonstrate that our newly developed library construction and computational methods can be applied to large genomes such as that of mouse.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377394/" 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/PMC2377394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cokus, Shawn J -- Feng, Suhua -- Zhang, Xiaoyu -- Chen, Zugen -- Merriman, Barry -- Haudenschild, Christian D -- Pradhan, Sriharsa -- Nelson, Stanley F -- Pellegrini, Matteo -- Jacobsen, Steven E -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 13;452(7184):215-9. doi: 10.1038/nature06745. Epub 2008 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18278030" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Arabidopsis/*genetics ; Base Sequence ; Computational Biology ; Cytosine/metabolism ; *DNA Methylation ; Gene Expression Regulation, Plant/genetics ; Gene Library ; Genome, Plant/*genetics ; Mice ; Mutation/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; Sulfites/*metabolism ; Uracil/metabolism
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  • 80
    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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  • 81
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-09-19
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071742/" 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/PMC3071742/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pfaff, Samuel L -- R01 NS037116/NS/NINDS NIH HHS/ -- R01 NS037116-03/NS/NINDS NIH HHS/ -- R01 NS037116-04/NS/NINDS NIH HHS/ -- R01 NS037116-04S1/NS/NINDS NIH HHS/ -- R01 NS037116-05/NS/NINDS NIH HHS/ -- R01 NS037116-06A1/NS/NINDS NIH HHS/ -- R01 NS037116-07/NS/NINDS NIH HHS/ -- R01 NS037116-07S1/NS/NINDS NIH HHS/ -- R01 NS037116-08/NS/NINDS NIH HHS/ -- R01 NS037116-08S1/NS/NINDS NIH HHS/ -- R01 NS037116-09/NS/NINDS NIH HHS/ -- R01 NS037116-10/NS/NINDS NIH HHS/ -- R01 NS054172/NS/NINDS NIH HHS/ -- R01 NS054172-01A2/NS/NINDS NIH HHS/ -- R01 NS054172-02/NS/NINDS NIH HHS/ -- R01 NS054172-03/NS/NINDS NIH HHS/ -- R01 NS054172-04/NS/NINDS NIH HHS/ -- R01 NS054172-05/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Sep 18;455(7211):295-7. doi: 10.1038/455295a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800121" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Cell Differentiation ; Forkhead Transcription Factors/chemistry/genetics/*metabolism ; Homeodomain Proteins/*metabolism ; Mice ; Motor Neurons/cytology/*metabolism ; Repressor Proteins/chemistry/genetics/metabolism ; Spinal Cord/*cytology/*embryology
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  • 82
    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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  • 83
    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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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geim, Andre -- England -- Nature. 2008 Jun 12;453(7197):850. doi: 10.1038/453850a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548048" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Europe ; Pan troglodytes ; *Public Policy ; Research/economics/*standards/trends
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  • 85
    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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  • 86
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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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  • 87
    Publication Date: 2008-02-15
    Description: Transcriptional activation of cytokines, such as type-I interferons (interferon (IFN)-alpha and IFN-beta), constitutes the first line of antiviral defence. Here we show that translational control is critical for induction of type-I IFN production. In mouse embryonic fibroblasts lacking the translational repressors 4E-BP1 and 4E-BP2, the threshold for eliciting type-I IFN production is lowered. Consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus and Sindbis virus is markedly suppressed. Furthermore, mice with both 4E- and 4E-BP2 genes (also known as Eif4ebp1 and Eif4ebp2, respectively) knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an enhanced type-I IFN production in plasmacytoid dendritic cells and the expression of IFN-regulated genes in the lungs. The enhanced type-I IFN response in 4E-BP1-/- 4E-BP2-/- double knockout mouse embryonic fibroblasts is caused by upregulation of interferon regulatory factor 7 (Irf7) messenger RNA translation. These findings highlight the role of 4E-BPs as negative regulators of type-I IFN production, via translational repression of Irf7 mRNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colina, Rodney -- Costa-Mattioli, Mauro -- Dowling, Ryan J O -- Jaramillo, Maritza -- Tai, Lee-Hwa -- Breitbach, Caroline J -- Martineau, Yvan -- Larsson, Ola -- Rong, Liwei -- Svitkin, Yuri V -- Makrigiannis, Andrew P -- Bell, John C -- Sonenberg, Nahum -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 20;452(7185):323-8. doi: 10.1038/nature06730. Epub 2008 Feb 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec H3G 1Y6, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18272964" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/metabolism ; Cells, Cultured ; Dendritic Cells/immunology ; Embryo, Mammalian/cytology ; Eukaryotic Initiation Factors/deficiency/genetics/metabolism ; Fibroblasts/virology ; Gene Deletion ; Immunity, Innate/genetics/*immunology ; Interferon Regulatory Factor-7/*biosynthesis/genetics/metabolism ; Interferon Type I/biosynthesis/immunology ; Mice ; Mice, Knockout ; Phosphoproteins/deficiency/genetics/metabolism ; *Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; Vesicular stomatitis Indiana virus/physiology ; Virus Physiological Phenomena ; Virus Replication
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  • 88
    Publication Date: 2008-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barbosa, Andre Frainer -- England -- Nature. 2008 May 15;453(7193):280. doi: 10.1038/453280b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18480789" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere/*chemistry ; Brazil ; Carbon Dioxide/analysis ; *Conservation of Natural Resources ; Federal Government ; *Greenhouse Effect ; Methane/analysis ; Power Plants/*trends ; *Trees
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  • 89
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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. doi: 10.1038/456281a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anniversaries and Special Events ; *Biological Evolution ; Biological Science Disciplines/history ; Genetic Speciation ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Ancient ; Selection, Genetic
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  • 90
    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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  • 91
    Publication Date: 2008-02-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Phillips, Patrick C -- England -- Nature. 2008 Feb 7;451(7179):640-1. doi: 10.1038/451640a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18256655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Caenorhabditis elegans/classification/embryology/*genetics/*physiology ; Chromosomes/genetics ; Crosses, Genetic ; Disorders of Sex Development ; Embryo Loss/genetics ; Embryo, Nonmammalian/embryology ; Female ; Genetic Markers/genetics ; Great Britain ; Hawaii ; Hybridization, Genetic ; Male ; Reproduction/genetics/physiology
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  • 92
    Publication Date: 2008-11-18
    Description: The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA. Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Emu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc-overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap-dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (also known as Cdc2l and PITSLRE), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Emu-Myc/+ mice. When accurate translational control is re-established in Emu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880952/" 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/PMC2880952/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barna, Maria -- Pusic, Aya -- Zollo, Ornella -- Costa, Maria -- Kondrashov, Nadya -- Rego, Eduardo -- Rao, Pulivarthi H -- Ruggero, Davide -- R01 HL085572/HL/NHLBI NIH HHS/ -- R01 HL085572-03/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 Dec 18;456(7224):971-5. doi: 10.1038/nature07449. Epub 2008 Nov 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry & Biophysics, University of California San Francisco, Rock Hall Room 384C, 1550 Fourth Street, San Francisco, California 94158-2517, USA. maria.barna@ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19011615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; B-Lymphocytes/cytology/metabolism/pathology ; Cell Division ; Cell Size ; Cells, Cultured ; Cytokinesis ; Gene Expression Regulation, Neoplastic ; Genes, myc/*genetics ; Genomic Instability ; Heterozygote ; Lymphoma/genetics/pathology ; Mice ; Mice, Inbred C57BL ; Mitosis ; Oncogene Protein p55(v-myc)/*genetics/*metabolism ; Precancerous Conditions/metabolism/pathology ; *Protein Biosynthesis ; Protein-Serine-Threonine Kinases/metabolism ; Ribosomal Proteins/*deficiency/*genetics
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  • 93
    Publication Date: 2008-02-14
    Description: Bats (Chiroptera) represent one of the largest and most diverse radiations of mammals, accounting for one-fifth of extant species. Although recent studies unambiguously support bat monophyly and consensus is rapidly emerging about evolutionary relationships among extant lineages, the fossil record of bats extends over 50 million years, and early evolution of the group remains poorly understood. Here we describe a new bat from the Early Eocene Green River Formation of Wyoming, USA, with features that are more primitive than seen in any previously known bat. The evolutionary pathways that led to flapping flight and echolocation in bats have been in dispute, and until now fossils have been of limited use in documenting transitions involved in this marked change in lifestyle. Phylogenetically informed comparisons of the new taxon with other bats and non-flying mammals reveal that critical morphological and functional changes evolved incrementally. Forelimb anatomy indicates that the new bat was capable of powered flight like other Eocene bats, but ear morphology suggests that it lacked their echolocation abilities, supporting a 'flight first' hypothesis for chiropteran evolution. The shape of the wings suggests that an undulating gliding-fluttering flight style may be primitive for bats, and the presence of a long calcar indicates that a broad tail membrane evolved early in Chiroptera, probably functioning as an additional airfoil rather than as a prey-capture device. Limb proportions and retention of claws on all digits indicate that the new bat may have been an agile climber that employed quadrupedal locomotion and under-branch hanging behaviour.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simmons, Nancy B -- Seymour, Kevin L -- Habersetzer, Jorg -- Gunnell, Gregg F -- England -- Nature. 2008 Feb 14;451(7180):818-21. doi: 10.1038/nature06549.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉American Museum of Natural History, Central Park West at 79th Street, New York, New York 10024, USA. simmons@amnh.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18270539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Chiroptera/*anatomy & histology/classification/*physiology ; Cochlea/anatomy & histology/physiology ; Echolocation/*physiology ; Extremities/anatomy & histology/physiology ; Flight, Animal/*physiology ; Fossils ; History, Ancient ; Phylogeny ; Rivers ; Wyoming
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  • 94
    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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  • 95
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    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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  • 96
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2008-02-29
    Description: Many free-ranging predators have to make foraging decisions with little, if any, knowledge of present resource distribution and availability. The optimal search strategy they should use to maximize encounter rates with prey in heterogeneous natural environments remains a largely unresolved issue in ecology. Levy walks are specialized random walks giving rise to fractal movement trajectories that may represent an optimal solution for searching complex landscapes. However, the adaptive significance of this putative strategy in response to natural prey distributions remains untested. Here we analyse over a million movement displacements recorded from animal-attached electronic tags to show that diverse marine predators-sharks, bony fishes, sea turtles and penguins-exhibit Levy-walk-like behaviour close to a theoretical optimum. Prey density distributions also display Levy-like fractal patterns, suggesting response movements by predators to prey distributions. Simulations show that predators have higher encounter rates when adopting Levy-type foraging in natural-like prey fields compared with purely random landscapes. This is consistent with the hypothesis that observed search patterns are adapted to observed statistical patterns of the landscape. This may explain why Levy-like behaviour seems to be widespread among diverse organisms, from microbes to humans, as a 'rule' that evolved in response to patchy resource distributions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sims, David W -- Southall, Emily J -- Humphries, Nicolas E -- Hays, Graeme C -- Bradshaw, Corey J A -- Pitchford, Jonathan W -- James, Alex -- Ahmed, Mohammed Z -- Brierley, Andrew S -- Hindell, Mark A -- Morritt, David -- Musyl, Michael K -- Righton, David -- Shepard, Emily L C -- Wearmouth, Victoria J -- Wilson, Rory P -- Witt, Matthew J -- Metcalfe, Julian D -- England -- Nature. 2008 Feb 28;451(7182):1098-102. doi: 10.1038/nature06518.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marine Biological Association of the United Kingdom, The Laboratory, Citadel Hill, Plymouth PL1 2PB, UK. dws@mba.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Euphausiacea ; *Feeding Behavior ; Fractals ; Gadiformes ; *Marine Biology ; *Models, Biological ; *Motor Activity ; Oceans and Seas ; Population Density ; *Predatory Behavior ; Probability ; Seals, Earless ; Sharks ; Spheniscidae ; Tuna ; Turtles
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  • 100
    Publication Date: 2008-05-27
    Description: Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested that cue-induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed 'incubation of cocaine craving': time-dependent increases in cue-induced cocaine-seeking over the first months after withdrawal from self-administered cocaine. Cocaine-seeking requires the activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the nucleus accumbens. Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 (GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2-lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2-lacking AMPA receptors causes increased reactivity of accumbens neurons to cocaine-related cues, leading to an intensification of drug craving and relapse.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574981/" 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/PMC2574981/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Conrad, Kelly L -- Tseng, Kuei Y -- Uejima, Jamie L -- Reimers, Jeremy M -- Heng, Li-Jun -- Shaham, Yavin -- Marinelli, Michela -- Wolf, Marina E -- DA00453/DA/NIDA NIH HHS/ -- DA015835/DA/NIDA NIH HHS/ -- DA020654/DA/NIDA NIH HHS/ -- DA09621/DA/NIDA NIH HHS/ -- Z01 DA000434-08/Intramural NIH HHS/ -- England -- Nature. 2008 Jul 3;454(7200):118-21. doi: 10.1038/nature06995. Epub 2008 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18500330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cocaine ; Cocaine-Related Disorders/genetics/metabolism/*physiopathology ; Cues ; Gene Expression Regulation ; Male ; Nucleus Accumbens/*metabolism/physiopathology ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; Receptors, AMPA/deficiency/genetics/*metabolism ; Self Administration ; Time Factors
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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