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  • 1
    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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    Electronic ISSN: 1476-4687
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  • 2
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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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    Electronic ISSN: 1476-4687
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  • 3
    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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  • 4
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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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  • 5
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Dec 4;456(7222):545. doi: 10.1038/456545a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052574" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/drug therapy/*epidemiology/*mortality ; Anti-HIV Agents/*supply & distribution ; Child ; *Federal Government ; Female ; Humans ; Politics ; Pregnancy ; *Public Policy ; South Africa/epidemiology
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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    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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  • 11
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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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  • 12
    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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  • 13
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Basu, Paroma -- Qiu, Jane -- Powell, Kendall -- England -- Nature. 2008 Oct 16;455(7215):1002-3. doi: 10.1038/nj7215-1002a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18938259" target="_blank"〉PubMed〈/a〉
    Keywords: Bottle Feeding/statistics & numerical data ; Breast Feeding/statistics & numerical data ; China ; Environmental Pollution/analysis ; Female ; Humans ; India/epidemiology ; *Organizations/organization & administration/statistics & numerical data ; *Research/manpower ; *Research Personnel ; Reward
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  • 14
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    Nature Publishing Group (NPG)
    Publication Date: 2008-07-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sloboda, John -- England -- Nature. 2008 Jul 3;454(7200):32-3. doi: 10.1038/454032a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Law, Politics and Justice, Keele University, Newcastle, Staffordshire ST5 5BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596790" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Culture ; Female ; Humans ; Music/*psychology ; Research/trends ; *Science
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  • 15
    Publication Date: 2008-08-15
    Description: Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiaomeng -- Harris, Robin E -- Bayston, Laura J -- Ashe, Hilary L -- BBS/B/11672/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2008 Sep 4;455(7209):72-7. doi: 10.1038/nature07214.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18701888" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Patterning ; Bone Morphogenetic Proteins/genetics/*metabolism ; Cell Count ; Collagen Type IV/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/embryology/genetics/*metabolism ; Female ; Male ; Ovary/cytology/metabolism ; Protein Binding ; *Signal Transduction ; Transforming Growth Factor beta/genetics/metabolism
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  • 16
    Publication Date: 2008-05-13
    Description: The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712082/" 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/PMC2712082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Keisuke -- Bernardi, Rosa -- Morotti, Alessandro -- Matsuoka, Sahoko -- Saglio, Giuseppe -- Ikeda, Yasuo -- Rosenblatt, Jacalyn -- Avigan, David E -- Teruya-Feldstein, Julie -- Pandolfi, Pier Paolo -- K99 CA139009/CA/NCI NIH HHS/ -- R00 CA139009/CA/NCI NIH HHS/ -- R37 CA071692/CA/NCI NIH HHS/ -- R37 CA071692-12/CA/NCI NIH HHS/ -- England -- Nature. 2008 Jun 19;453(7198):1072-8. doi: 10.1038/nature07016. Epub 2008 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18469801" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Arsenicals/pharmacology/therapeutic use ; Cell Line ; Coculture Techniques ; Female ; Gene Expression Regulation, Neoplastic ; Hematopoietic Stem Cells/pathology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism/*pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/metabolism/*pathology ; Nuclear Proteins/antagonists & inhibitors/deficiency/genetics/*metabolism ; Oxides/pharmacology/therapeutic use ; Recurrence ; Regeneration ; Transcription Factors/antagonists & inhibitors/deficiency/genetics/*metabolism ; Tumor Suppressor Proteins/antagonists & ; inhibitors/deficiency/genetics/*metabolism
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  • 17
    Publication Date: 2008-11-14
    Description: Our decisions are guided by information learnt from our environment. This information may come via personal experiences of reward, but also from the behaviour of social partners. Social learning is widely held to be distinct from other forms of learning in its mechanism and neural implementation; it is often assumed to compete with simpler mechanisms, such as reward-based associative learning, to drive behaviour. Recently, neural signals have been observed during social exchange reminiscent of signals seen in studies of associative learning. Here we demonstrate that social information may be acquired using the same associative processes assumed to underlie reward-based learning. We find that key computational variables for learning in the social and reward domains are processed in a similar fashion, but in parallel neural processing streams. Two neighbouring divisions of the anterior cingulate cortex were central to learning about social and reward-based information, and for determining the extent to which each source of information guides behaviour. When making a decision, however, the information learnt using these parallel streams was combined within ventromedial prefrontal cortex. These findings suggest that human social valuation can be realized by means of the same associative processes previously established for learning other, simpler, features of the environment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2605577/" 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/PMC2605577/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Behrens, Timothy E J -- Hunt, Laurence T -- Woolrich, Mark W -- Rushworth, Matthew F S -- G0501316/Medical Research Council/United Kingdom -- G0501316(75487)/Medical Research Council/United Kingdom -- G0600994/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Nov 13;456(7219):245-9. doi: 10.1038/nature07538.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉FMRIB Centre, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. behrens@fmrib.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19005555" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Female ; Humans ; Learning/*physiology ; Male ; Middle Aged ; Models, Statistical ; Prefrontal Cortex/physiology ; Reward ; *Social Behavior
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  • 18
    Publication Date: 2008-11-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coulson, Tim -- Malo, Aurelio -- England -- Nature. 2008 Nov 6;456(7218):43-4. doi: 10.1038/456043a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/*physiology ; *Ecosystem ; Female ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Norway ; Population Dynamics ; Seasons ; Snow ; Temperature
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  • 19
    Publication Date: 2008-04-11
    Description: There exists controversy over the nature of haematopoietic progenitors of T cells. Most T cells develop in the thymus, but the lineage potential of thymus-colonizing progenitors is unknown. One approach to resolving this question is to determine the lineage potentials of the earliest thymic progenitors (ETPs). Previous work has shown that ETPs possess T and natural killer lymphoid potentials, and rare subsets of ETPs also possess B lymphoid potential, suggesting an origin from lymphoid-restricted progenitor cells. However, whether ETPs also possess myeloid potential is unknown. Here we show that nearly all ETPs in adult mice possess both T and myeloid potential in clonal assays. The existence of progenitors possessing T and myeloid potential within the thymus is incompatible with the current dominant model of haematopoiesis, in which T cells are proposed to arise from lymphoid-. Our results indicate that alternative models for lineage commitment during haematopoiesis must be considered.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, J Jeremiah -- Bhandoola, Avinash -- England -- Nature. 2008 Apr 10;452(7188):764-7. doi: 10.1038/nature06840.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401411" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Lineage ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/cytology ; Female ; Granulocytes/cytology ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology/metabolism ; Macrophages/cytology ; Mice ; Models, Biological ; Myeloid Cells/*cytology/metabolism ; Stromal Cells/cytology ; T-Lymphocytes/*cytology/metabolism ; Thymus Gland/*cytology
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  • 20
    Publication Date: 2008-06-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maher, Brendan -- England -- Nature. 2008 Jun 12;453(7197):828-9. doi: 10.1038/453828a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548027" target="_blank"〉PubMed〈/a〉
    Keywords: Embryonic Stem Cells/*cytology ; Female ; Humans ; Oocyte Donation/*economics/ethics/*legislation & jurisprudence/statistics & ; numerical data ; Ovum/cytology ; *Research Embryo Creation/economics/ethics/legislation & jurisprudence ; *State Government ; United States
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  • 21
    Publication Date: 2008-04-04
    Description: In vertebrate oocytes, meiotic progression is driven by the sequential translational activation of maternal messenger RNAs stored in the cytoplasm. This activation is mainly induced by the cytoplasmic elongation of their poly(A) tails, which is mediated by the cytoplasmic polyadenylation element (CPE) present in their 3' untranslated regions. In Xenopus oocytes, sequential phase-specific translation of CPE-regulated mRNAs is required to activate the maturation-promoting factor, which in turn mediates entry into the two consecutive meiotic metaphases (MI and MII). Here we report a genome-wide functional screening to identify previously unknown mRNAs cytoplasmically polyadenylated at meiotic phase transitions. A significant fraction of transcripts containing, in addition to CPEs, (A + U)-rich element (ARE) sequences (characteristic of mRNAs regulated by deadenylation) were identified. Among these is the mRNA encoding C3H-4, an ARE-binding protein that we find to accumulate in MI and the ablation of which induces meiotic arrest. Our results suggest that C3H-4 recruits the CCR4 deadenylase complex to ARE-containing mRNAs and this, in turn, causes shortening of poly(A) tails. We also show that the opposing activities of the CPEs and the AREs define the precise activation times of the mRNAs encoding the anaphase-promoting complex inhibitors Emi1 and Emi2 during distinct phases of the meiotic cycle. Taken together, our results show that an 'early' wave of cytoplasmic polyadenylation activates a negative feedback loop by activating the synthesis of C3H-4, which in turn would recruit the deadenylase complex to mRNAs containing both CPEs and AREs. This negative feedback loop is required to exit from metaphase into interkinesis and for meiotic progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Belloc, Eulalia -- Mendez, Raul -- England -- Nature. 2008 Apr 24;452(7190):1017-21. doi: 10.1038/nature06809. Epub 2008 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG), Pompeu Fabra University (UPF), C/Dr Aiguader 88, 08003, Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18385675" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/genetics ; F-Box Proteins/genetics ; Feedback, Physiological/*genetics ; Female ; Genome/genetics ; *Meiosis/genetics ; *Metaphase ; Oocytes/*cytology/metabolism ; Phosphoproteins/biosynthesis/genetics/metabolism ; *Polyadenylation/genetics ; Protein Biosynthesis/genetics ; RNA, Messenger/genetics/metabolism ; Transcription Factors/metabolism ; Xenopus Proteins/biosynthesis/genetics/metabolism ; Xenopus laevis ; mRNA Cleavage and Polyadenylation Factors/metabolism
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  • 22
    Publication Date: 2008-10-03
    Description: The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Majo, Francois -- Rochat, Ariane -- Nicolas, Michael -- Jaoude, Georges Abou -- Barrandon, Yann -- England -- Nature. 2008 Nov 13;456(7219):250-4. doi: 10.1038/nature07406. Epub 2008 Oct 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne CH, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18830243" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Cattle ; Cells, Cultured ; Child, Preschool ; Clone Cells ; Corneal Transplantation ; Epithelium, Corneal/*cytology/metabolism ; Female ; Gene Expression Regulation ; Humans ; Infant ; Keratinocytes/cytology/metabolism ; Male ; Mice ; Mice, SCID ; Models, Biological ; Multipotent Stem Cells/*cytology ; Proteins/metabolism ; Rats ; Swine
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  • 23
    Publication Date: 2008-01-22
    Description: Understanding the mechanisms that determine an individual's sex remains a primary challenge for evolutionary biology. Chromosome-based systems (genotypic sex determination) that generate roughly equal numbers of sons and daughters accord with theory, but the adaptive significance of environmental sex determination (that is, when embryonic environmental conditions determine offspring sex, ESD) is a major unsolved problem. Theoretical models predict that selection should favour ESD over genotypic sex determination when the developmental environment differentially influences male versus female fitness (that is, the Charnov-Bull model), but empirical evidence for this hypothesis remains elusive in amniote vertebrates--the clade in which ESD is most prevalent. Here we provide the first substantial empirical support for this model by showing that incubation temperatures influence reproductive success of males differently than that of females in a short-lived lizard (Amphibolurus muricatus, Agamidae) with temperature-dependent sex determination. We incubated eggs at a variety of temperatures, and de-confounded sex and incubation temperature by using hormonal manipulations to embryos. We then raised lizards in field enclosures and quantified their lifetime reproductive success. Incubation temperature affected reproductive success differently in males versus females in exactly the way predicted by theory: the fitness of each sex was maximized by the incubation temperature that produces that sex. Our results provide unequivocal empirical support for the Charnov-Bull model for the adaptive significance of temperature-dependent sex determination in amniote vertebrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warner, D A -- Shine, R -- England -- Nature. 2008 Jan 31;451(7178):566-8. doi: 10.1038/nature06519. Epub 2008 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Sydney, Sydney, New South Wales 2006, Australia. dwarner@iastate.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18204437" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/physiology ; Adaptation, Physiological/*physiology ; Animals ; Body Size ; Fadrozole/pharmacology ; Female ; Lizards/*embryology/*physiology ; Male ; Models, Biological ; Ovum/drug effects/growth & development ; Reproduction/physiology ; Sex Characteristics ; Sex Differentiation/*physiology ; *Temperature
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  • 24
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wassarman, Paul M -- England -- Nature. 2008 Dec 4;456(7222):586-7. doi: 10.1038/456586a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Conserved Sequence ; Crystallography, X-Ray ; Egg Proteins/*chemistry/genetics/*metabolism ; Female ; Fertilization/physiology ; Male ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; Mice ; Ovum/*chemistry/*metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Spermatozoa/metabolism
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  • 25
    Publication Date: 2008-05-10
    Description: We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803040/" 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/PMC2803040/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Wesley C -- Hillier, LaDeana W -- Marshall Graves, Jennifer A -- Birney, Ewan -- Ponting, Chris P -- Grutzner, Frank -- Belov, Katherine -- Miller, Webb -- Clarke, Laura -- Chinwalla, Asif T -- Yang, Shiaw-Pyng -- Heger, Andreas -- Locke, Devin P -- Miethke, Pat -- Waters, Paul D -- Veyrunes, Frederic -- Fulton, Lucinda -- Fulton, Bob -- Graves, Tina -- Wallis, John -- Puente, Xose S -- Lopez-Otin, Carlos -- Ordonez, Gonzalo R -- Eichler, Evan E -- Chen, Lin -- Cheng, Ze -- Deakin, Janine E -- Alsop, Amber -- Thompson, Katherine -- Kirby, Patrick -- Papenfuss, Anthony T -- Wakefield, Matthew J -- Olender, Tsviya -- Lancet, Doron -- Huttley, Gavin A -- Smit, Arian F A -- Pask, Andrew -- Temple-Smith, Peter -- Batzer, Mark A -- Walker, Jerilyn A -- Konkel, Miriam K -- Harris, Robert S -- Whittington, Camilla M -- Wong, Emily S W -- Gemmell, Neil J -- Buschiazzo, Emmanuel -- Vargas Jentzsch, Iris M -- Merkel, Angelika -- Schmitz, Juergen -- Zemann, Anja -- Churakov, Gennady -- Kriegs, Jan Ole -- Brosius, Juergen -- Murchison, Elizabeth P -- Sachidanandam, Ravi -- Smith, Carly -- Hannon, Gregory J -- Tsend-Ayush, Enkhjargal -- McMillan, Daniel -- Attenborough, Rosalind -- Rens, Willem -- Ferguson-Smith, Malcolm -- Lefevre, Christophe M -- Sharp, Julie A -- Nicholas, Kevin R -- Ray, David A -- Kube, Michael -- Reinhardt, Richard -- Pringle, Thomas H -- Taylor, James -- Jones, Russell C -- Nixon, Brett -- Dacheux, Jean-Louis -- Niwa, Hitoshi -- Sekita, Yoko -- Huang, Xiaoqiu -- Stark, Alexander -- Kheradpour, Pouya -- Kellis, Manolis -- Flicek, Paul -- Chen, Yuan -- Webber, Caleb -- Hardison, Ross -- Nelson, Joanne -- Hallsworth-Pepin, Kym -- Delehaunty, Kim -- Markovic, Chris -- Minx, Pat -- Feng, Yucheng -- Kremitzki, Colin -- Mitreva, Makedonka -- Glasscock, Jarret -- Wylie, Todd -- Wohldmann, Patricia -- Thiru, Prathapan -- Nhan, Michael N -- Pohl, Craig S -- Smith, Scott M -- Hou, Shunfeng -- Nefedov, Mikhail -- de Jong, Pieter J -- Renfree, Marilyn B -- Mardis, Elaine R -- Wilson, Richard K -- 062023/Wellcome Trust/United Kingdom -- HG002238/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- P01 CA013106/CA/NCI NIH HHS/ -- P01 CA013106-37/CA/NCI NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG004037-02/HG/NHGRI NIH HHS/ -- R01HG02385/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2008 May 8;453(7192):175-83. doi: 10.1038/nature06936.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. wwarren@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Dentition ; *Evolution, Molecular ; Female ; Genome/*genetics ; Genomic Imprinting/genetics ; Humans ; Immunity/genetics ; Male ; Mammals/genetics ; MicroRNAs/genetics ; Milk Proteins/genetics ; Phylogeny ; Platypus/*genetics/immunology/physiology ; Receptors, Odorant/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Reptiles/genetics ; Sequence Analysis, DNA ; Spermatozoa/metabolism ; Venoms/genetics ; Zona Pellucida/metabolism
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  • 26
    Publication Date: 2008-04-12
    Description: RNA interference (RNAi) is a mechanism by which double-stranded RNAs (dsRNAs) suppress specific transcripts in a sequence-dependent manner. dsRNAs are processed by Dicer to 21-24-nucleotide small interfering RNAs (siRNAs) and then incorporated into the argonaute (Ago) proteins. Gene regulation by endogenous siRNAs has been observed only in organisms possessing RNA-dependent RNA polymerase (RdRP). In mammals, where no RdRP activity has been found, biogenesis and function of endogenous siRNAs remain largely unknown. Here we show, using mouse oocytes, that endogenous siRNAs are derived from naturally occurring dsRNAs and have roles in the regulation of gene expression. By means of deep sequencing, we identify a large number of both approximately 25-27-nucleotide Piwi-interacting RNAs (piRNAs) and approximately 21-nucleotide siRNAs corresponding to messenger RNAs or retrotransposons in growing oocytes. piRNAs are bound to Mili and have a role in the regulation of retrotransposons. siRNAs are exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming dsRNA structures. Inverted repeat structures, bidirectional transcription and antisense transcripts from various loci are sources of the dsRNAs. Some precursor transcripts of siRNAs are derived from expressed pseudogenes, indicating that one role of pseudogenes is to adjust the level of the founding source mRNA through RNAi. Loss of Dicer or Ago2 results in decreased levels of siRNAs and increased levels of retrotransposon and protein-coding transcripts complementary to the siRNAs. Thus, the RNAi pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes. Our results reveal a role for endogenous siRNAs in mammalian oocytes and show that organisms lacking RdRP activity can produce functional endogenous siRNAs from naturally occurring dsRNAs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watanabe, Toshiaki -- Totoki, Yasushi -- Toyoda, Atsushi -- Kaneda, Masahiro -- Kuramochi-Miyagawa, Satomi -- Obata, Yayoi -- Chiba, Hatsune -- Kohara, Yuji -- Kono, Tomohiro -- Nakano, Toru -- Surani, M Azim -- Sakaki, Yoshiyuki -- Sasaki, Hiroyuki -- England -- Nature. 2008 May 22;453(7194):539-43. doi: 10.1038/nature06908. Epub 2008 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima 411-8540, Japan. toshwata@lab.nig.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18404146" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Eukaryotic Initiation Factor-2/deficiency/genetics/metabolism ; Female ; Gene Expression Regulation, Developmental ; Gene Library ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Oocytes/growth & development/*metabolism ; Polymerase Chain Reaction ; Pseudogenes/genetics ; *RNA Interference ; RNA, Double-Stranded/*genetics/*metabolism ; RNA, Messenger/*genetics/metabolism ; RNA, Small Interfering/*genetics/*metabolism ; Retroelements/genetics ; Ribonuclease III/deficiency/genetics/metabolism
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  • 27
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mandavilli, Apoorva -- England -- Nature. 2008 May 29;453(7195):581-2. doi: 10.1038/453581a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509413" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Defensins/metabolism ; *Ecosystem ; Feces/*microbiology ; Female ; Humans ; Infant, Newborn ; Intestines/*microbiology/*transplantation ; Models, Biological ; Nod2 Signaling Adaptor Protein/genetics/metabolism
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  • 28
    Publication Date: 2008-05-02
    Description: Half a century ago, the apical ectodermal ridge (AER) at the distal tip of the tetrapod limb bud was shown to produce signals necessary for development along the proximal-distal (P-D) axis, but how these signals influence limb patterning is still much debated. Fibroblast growth factor (FGF) gene family members are key AER-derived signals, with Fgf4, Fgf8, Fgf9 and Fgf17 expressed specifically in the mouse AER. Here we demonstrate that mouse limbs lacking Fgf4, Fgf9 and Fgf17 have normal skeletal pattern, indicating that Fgf8 is sufficient among AER-FGFs to sustain normal limb formation. Inactivation of Fgf8 alone causes a mild skeletal phenotype; however, when we also removed different combinations of the other AER-FGF genes, we obtained unexpected skeletal phenotypes of increasing severity, reflecting the contribution that each FGF can make to the total AER-FGF signal. Analysis of the compound mutant limb buds revealed that, in addition to sustaining cell survival, AER-FGFs regulate P-D-patterning gene expression during early limb bud development, providing genetic evidence that AER-FGFs function to specify a distal domain and challenging the long-standing hypothesis that AER-FGF signalling is permissive rather than instructive for limb patterning. We discuss how a two-signal model for P-D patterning can be integrated with the concept of early specification to explain the genetic data presented here.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631409/" 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/PMC2631409/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mariani, Francesca V -- Ahn, Christina P -- Martin, Gail R -- F32 HD008696/HD/NICHD NIH HHS/ -- F32 HD008696-01/HD/NICHD NIH HHS/ -- F32 HD008696-02/HD/NICHD NIH HHS/ -- F32 HD008696-03/HD/NICHD NIH HHS/ -- R01 HD034380/HD/NICHD NIH HHS/ -- R01 HD034380-05/HD/NICHD NIH HHS/ -- R01 HD034380-06/HD/NICHD NIH HHS/ -- R01 HD034380-07/HD/NICHD NIH HHS/ -- R01 HD034380-08/HD/NICHD NIH HHS/ -- R01 HD034380-09/HD/NICHD NIH HHS/ -- R01 HD34380/HD/NICHD NIH HHS/ -- England -- Nature. 2008 May 15;453(7193):401-5. doi: 10.1038/nature06876. Epub 2008 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, California 94158-2324, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18449196" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Patterning/*genetics/*physiology ; Bone and Bones/embryology/metabolism ; Cell Survival ; Female ; Fibroblast Growth Factor 8/deficiency/genetics/*metabolism ; Fibroblast Growth Factors/deficiency/genetics/*metabolism ; Homeodomain Proteins/genetics ; Limb Buds/cytology/*embryology/metabolism ; Male ; Mice ; Neoplasm Proteins/genetics ; Organ Size ; Signal Transduction
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  • 29
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    Nature Publishing Group (NPG)
    Publication Date: 2008-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berry, Donald A -- England -- Nature. 2008 Aug 7;454(7205):692-3. doi: 10.1038/454692a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Quantitative Sciences, Department of Biostatistics, MD Anderson Cancer Center, University of Texas, 1400 Pressler Street, Houston, Texas 77030-1402, USA. dberry@mdanderson.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18685682" target="_blank"〉PubMed〈/a〉
    Keywords: Doping in Sports/*prevention & control ; False Positive Reactions ; Female ; Humans ; Male ; Probability ; Reproducibility of Results ; Sample Size ; Sensitivity and Specificity ; *Sports/ethics/standards ; Substance Abuse Detection/methods/*standards
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  • 30
    Publication Date: 2008-09-23
    Description: Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T-cell-mediated destruction of insulin-producing beta-cells. Its incidence has increased during the past several decades in developed countries, suggesting that changes in the environment (including the human microbial environment) may influence disease pathogenesis. The incidence of spontaneous T1D in non-obese diabetic (NOD) mice can be affected by the microbial environment in the animal housing facility or by exposure to microbial stimuli, such as injection with mycobacteria or various microbial products. Here we show that specific pathogen-free NOD mice lacking MyD88 protein (an adaptor for multiple innate immune receptors that recognize microbial stimuli) do not develop T1D. The effect is dependent on commensal microbes because germ-free MyD88-negative NOD mice develop robust diabetes, whereas colonization of these germ-free MyD88-negative NOD mice with a defined microbial consortium (representing bacterial phyla normally present in human gut) attenuates T1D. We also find that MyD88 deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of specific pathogen-free MyD88-negative NOD donors attenuates T1D in germ-free NOD recipients. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574766/" 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/PMC2574766/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wen, Li -- Ley, Ruth E -- Volchkov, Pavel Yu -- Stranges, Peter B -- Avanesyan, Lia -- Stonebraker, Austin C -- Hu, Changyun -- Wong, F Susan -- Szot, Gregory L -- Bluestone, Jeffrey A -- Gordon, Jeffrey I -- Chervonsky, Alexander V -- DK063452/DK/NIDDK NIH HHS/ -- DK30292/DK/NIDDK NIH HHS/ -- DK42086/DK/NIDDK NIH HHS/ -- DK45735/DK/NIDDK NIH HHS/ -- DK70977/DK/NIDDK NIH HHS/ -- P30 DK042086/DK/NIDDK NIH HHS/ -- P30 DK042086-16/DK/NIDDK NIH HHS/ -- P30 DK045735/DK/NIDDK NIH HHS/ -- P30 DK045735-10/DK/NIDDK NIH HHS/ -- P30 DK045735-119006/DK/NIDDK NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-07/DK/NIDDK NIH HHS/ -- P30 DK056341-08/DK/NIDDK NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- P30 DK063720-01/DK/NIDDK NIH HHS/ -- P30 DK63720/DK/NIDDK NIH HHS/ -- R01 DK030292/DK/NIDDK NIH HHS/ -- R01 DK030292-24/DK/NIDDK NIH HHS/ -- R01 DK070977/DK/NIDDK NIH HHS/ -- R01 DK070977-04/DK/NIDDK NIH HHS/ -- R21 DK063452/DK/NIDDK NIH HHS/ -- R21 DK063452-02/DK/NIDDK NIH HHS/ -- R37 AI046643/AI/NIAID NIH HHS/ -- R37 AI046643-10/AI/NIAID NIH HHS/ -- R37 AI46643/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1109-13. doi: 10.1038/nature07336. Epub 2008 Sep 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18806780" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/classification/genetics/*immunology/isolation & purification ; CD8-Positive T-Lymphocytes/immunology ; Diabetes Mellitus, Type 1/genetics/*immunology/*microbiology ; Female ; Immunity, Innate/genetics/*immunology ; Interferon-gamma/immunology ; Intestines/*microbiology ; Islets of Langerhans/pathology ; Male ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Molecular Sequence Data ; Myeloid Differentiation Factor 88/genetics ; Phylogeny ; Specific Pathogen-Free Organisms ; Time Factors
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  • 31
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    Nature Publishing Group (NPG)
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Dan -- England -- Nature. 2008 Jan 31;451(7178):512-5. doi: 10.1038/451512a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235473" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Aggression/*physiology/psychology ; Altruism ; Anger/physiology ; Animals ; Antisocial Personality Disorder/physiopathology ; *Biological Evolution ; Conflict (Psychology) ; Female ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Medieval ; *Homicide/history/psychology ; Humans ; Male ; Models, Biological ; Morals ; Pan troglodytes/physiology ; Prefrontal Cortex/anatomy & histology/physiology ; Sex Characteristics ; United Nations ; Violence/psychology ; Warfare
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  • 32
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crews, David -- Bull, James J -- England -- Nature. 2008 Jan 31;451(7178):527-8. doi: 10.1038/451527a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235487" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*physiology ; Animals ; Body Size ; Fadrozole/pharmacology ; Female ; Lizards/*embryology/*physiology ; Male ; Models, Biological ; Ovum/drug effects/growth & development ; Reproduction/physiology ; Sex Characteristics ; Sex Differentiation/*physiology ; *Temperature
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  • 33
    Publication Date: 2008-02-01
    Description: Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wendt, Kerstin S -- Yoshida, Keisuke -- Itoh, Takehiko -- Bando, Masashige -- Koch, Birgit -- Schirghuber, Erika -- Tsutsumi, Shuichi -- Nagae, Genta -- Ishihara, Ko -- Mishiro, Tsuyoshi -- Yahata, Kazuhide -- Imamoto, Fumio -- Aburatani, Hiroyuki -- Nakao, Mitsuyoshi -- Imamoto, Naoko -- Maeshima, Kazuhiro -- Shirahige, Katsuhiko -- Peters, Jan-Michael -- England -- Nature. 2008 Feb 14;451(7180):796-801. doi: 10.1038/nature06634. Epub 2008 Jan 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Dr. Bohr Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235444" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Brain/cytology/metabolism ; Cell Cycle Proteins/*metabolism ; Cell Differentiation ; Chromosomal Proteins, Non-Histone/*metabolism ; Consensus Sequence/genetics ; DNA/genetics/metabolism ; DNA-Binding Proteins/*metabolism ; Enhancer Elements, Genetic/genetics ; Female ; Gene Expression Regulation/*genetics ; Genome, Human/genetics ; HeLa Cells ; Humans ; Insulin-Like Growth Factor II/genetics ; Mice ; Mitosis ; Mothers ; Nuclear Proteins/*metabolism ; Promoter Regions, Genetic/genetics ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Repressor Proteins/*metabolism ; Transcription, Genetic/*genetics
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  • 34
    Publication Date: 2008-09-06
    Description: Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671642/" 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/PMC2671642/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cancer Genome Atlas Research Network -- R01 CA099041/CA/NCI NIH HHS/ -- R01 CA099041-05/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U24 CA126543-01/CA/NCI NIH HHS/ -- U24 CA126544/CA/NCI NIH HHS/ -- U24 CA126544-01/CA/NCI NIH HHS/ -- U24 CA126546/CA/NCI NIH HHS/ -- U24 CA126546-01/CA/NCI NIH HHS/ -- U24 CA126551-01/CA/NCI NIH HHS/ -- U24 CA126554/CA/NCI NIH HHS/ -- U24 CA126554-01/CA/NCI NIH HHS/ -- U24 CA126561/CA/NCI NIH HHS/ -- U24 CA126561-01/CA/NCI NIH HHS/ -- U24 CA126563/CA/NCI NIH HHS/ -- U24 CA126563-01/CA/NCI NIH HHS/ -- U24CA126543/CA/NCI NIH HHS/ -- U24CA126544/CA/NCI NIH HHS/ -- U24CA126546/CA/NCI NIH HHS/ -- U24CA126551/CA/NCI NIH HHS/ -- U24CA126554/CA/NCI NIH HHS/ -- U24CA126561/CA/NCI NIH HHS/ -- U24CA126563/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-01/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-05/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273-01/HG/NHGRI NIH HHS/ -- U54HG003067/HG/NHGRI NIH HHS/ -- U54HG003079/HG/NHGRI NIH HHS/ -- U54HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1061-8. doi: 10.1038/nature07385. Epub 2008 Sep 4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772890" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/*genetics ; DNA Methylation ; DNA Modification Methylases/genetics ; DNA Repair/genetics ; DNA Repair Enzymes/genetics ; Female ; Gene Dosage ; *Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Genes, erbB-1/genetics ; Genome, Human/genetics ; *Genomics ; Glioblastoma/*genetics ; Humans ; Male ; Middle Aged ; Models, Molecular ; Mutation/genetics ; Neurofibromin 1/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Protein Structure, Tertiary ; Retrospective Studies ; Signal Transduction/genetics ; Tumor Suppressor Proteins/genetics
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  • 35
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    Nature Publishing Group (NPG)
    Publication Date: 2008-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marris, Emma -- England -- Nature. 2008 Mar 27;452(7186):394-5. doi: 10.1038/452394a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368084" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Domestic ; Animals, Wild ; Anura/*physiology ; Biodiversity ; Conservation of Natural Resources/*methods ; *Ecosystem ; Extinction, Biological ; Female ; Male ; Population Density
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  • 36
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    Nature Publishing Group (NPG)
    Publication Date: 2008-09-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitfield, John -- England -- Nature. 2008 Sep 18;455(7211):281-4. doi: 10.1038/455281a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18800108" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Austria ; *Biological Evolution ; Biology/*trends ; Congresses as Topic ; Female ; Heredity ; Humans ; Male ; *Models, Biological ; Selection, Genetic
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  • 37
    Publication Date: 2008-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martens, Koen -- Schon, Isa -- England -- Nature. 2008 May 29;453(7195):587. doi: 10.1038/453587b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crustacea/anatomy & histology/*physiology ; Female ; History, 19th Century ; History, Ancient ; Male ; Reproduction, Asexual/*physiology ; Rotifera/*physiology ; Time Factors
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  • 38
    Publication Date: 2008-05-13
    Description: Despite intense investigation, mechanisms that facilitate the emergence of the pre-eclampsia phenotype in women are still unknown. Placental hypoxia, hypertension, proteinuria and oedema are the principal clinical features of this disease. It is speculated that hypoxia-driven disruption of the angiogenic balance involving vascular endothelial growth factor (VEGF)/placenta-derived growth factor (PLGF) and soluble Fms-like tyrosine kinase-1 (sFLT-1, the soluble form of VEGF receptor 1) might contribute to some of the maternal symptoms of pre-eclampsia. However, pre-eclampsia does not develop in all women with high sFLT-1 or low PLGF levels, and it also occurs in some women with low sFLT-1 and high PLGF levels. Moreover, recent experiments strongly suggest that several soluble factors affecting the vasculature are probably elevated because of placental hypoxia in the pre-eclamptic women, indicating that upstream molecular defect(s) may contribute to pre-eclampsia. Here we show that pregnant mice deficient in catechol-O-methyltransferase (COMT) show a pre-eclampsia-like phenotype resulting from an absence of 2-methoxyoestradiol (2-ME), a natural metabolite of oestradiol that is elevated during the third trimester of normal human pregnancy. 2-ME ameliorates all pre-eclampsia-like features without toxicity in the Comt(-/-) pregnant mice and suppresses placental hypoxia, hypoxia-inducible factor-1alpha expression and sFLT-1 elevation. The levels of COMT and 2-ME are significantly lower in women with severe pre-eclampsia. Our studies identify a genetic mouse model for pre-eclampsia and suggest that 2-ME may have utility as a plasma and urine diagnostic marker for this disease, and may also serve as a therapeutic supplement to prevent or treat this disorder.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kanasaki, Keizo -- Palmsten, Kristin -- Sugimoto, Hikaru -- Ahmad, Shakil -- Hamano, Yuki -- Xie, Liang -- Parry, Samuel -- Augustin, Hellmut G -- Gattone, Vincent H -- Folkman, Judah -- Strauss, Jerome F -- Kalluri, Raghu -- DK 13193/DK/NIDDK NIH HHS/ -- DK 55001/DK/NIDDK NIH HHS/ -- DK 61688/DK/NIDDK NIH HHS/ -- DK 62987/DK/NIDDK NIH HHS/ -- G0700288/Medical Research Council/United Kingdom -- R01 DK055001/DK/NIDDK NIH HHS/ -- R01 DK061688/DK/NIDDK NIH HHS/ -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2008 Jun 19;453(7198):1117-21. doi: 10.1038/nature06951. Epub 2008 May 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18469803" target="_blank"〉PubMed〈/a〉
    Keywords: Albumins/analysis ; Animals ; Anoxia/metabolism ; Blood Pressure ; Catechol O-Methyltransferase/analysis/*deficiency/genetics ; Creatinine/urine ; Disease Models, Animal ; Estradiol/*analogs & derivatives/blood/*deficiency/urine ; Female ; Humans ; Hypertension ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Killer Cells, Natural/immunology ; Litter Size ; Male ; Mice ; Placenta/enzymology/pathology ; Pre-Eclampsia/blood/enzymology/*metabolism/urine ; Pregnancy ; Proteinuria ; Vascular Endothelial Growth Factor Receptor-1/blood
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  • 39
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    Nature Publishing Group (NPG)
    Publication Date: 2008-05-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2008 May 22;453(7194):435. doi: 10.1038/453435a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497781" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/genetics/*physiology ; Animals ; Dengue/*prevention & control/*transmission ; Evaluation Studies as Topic ; Female ; Fertility/genetics/*physiology ; *Genetic Engineering ; Humans ; Malaysia ; Male ; Mosquito Control/*methods
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  • 40
    Publication Date: 2008-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cyranoski, David -- England -- Nature. 2008 Mar 27;452(7186):406-8. doi: 10.1038/452406a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18368095" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Culture Techniques ; Cell Differentiation ; Cell- and Tissue-Based Therapy/ethics/trends ; Embryonic Stem Cells/cytology/transplantation ; Female ; Humans ; Male ; Mice ; Pluripotent Stem Cells/*cytology/transplantation ; Reproductive Techniques, Assisted/ethics/trends ; Research Embryo Creation/ethics/legislation & jurisprudence ; Skin/cytology ; Transduction, Genetic/methods/standards
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  • 41
    Publication Date: 2008-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaplan, Matt -- England -- Nature. 2008 Feb 14;451(7180):760-2. doi: 10.1038/451760a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18272991" target="_blank"〉PubMed〈/a〉
    Keywords: Courtship/*psychology ; Decision Making ; Female ; Humans ; *Love ; Male ; Social Sciences/*methods ; Surveys and Questionnaires ; Time Factors
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  • 42
    Publication Date: 2008-05-02
    Description: Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graupera, Mariona -- Guillermet-Guibert, Julie -- Foukas, Lazaros C -- Phng, Li-Kun -- Cain, Robert J -- Salpekar, Ashreena -- Pearce, Wayne -- Meek, Stephen -- Millan, Jaime -- Cutillas, Pedro R -- Smith, Andrew J H -- Ridley, Anne J -- Ruhrberg, Christiana -- Gerhardt, Holger -- Vanhaesebroeck, Bart -- BB/C505659/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/C505659/2/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0601093/Medical Research Council/United Kingdom -- G0601093(79633)/Medical Research Council/United Kingdom -- G0700711/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2008 May 29;453(7195):662-6. doi: 10.1038/nature06892. Epub 2008 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18449193" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Movement ; Cells, Cultured ; Class I Phosphatidylinositol 3-Kinases ; Endothelial Cells/*cytology/*enzymology ; Female ; Humans ; Mice ; *Neovascularization, Physiologic ; Phosphatidylinositol 3-Kinases/genetics/*metabolism ; RNA Interference ; Rats ; Signal Transduction/drug effects ; Vascular Endothelial Growth Factor A/pharmacology ; Wounds and Injuries ; rho GTP-Binding Proteins/metabolism
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  • 43
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-07-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Jul 17;454(7202):253. doi: 10.1038/454253a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18633362" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Fertilization in Vitro/legislation & jurisprudence/standards/*trends ; Genetic Testing ; Humans ; Infertility/therapy ; Male ; Pregnancy ; Registries
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  • 44
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2008 Oct 30;455(7217):1156-7. doi: 10.1038/4551156a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971985" target="_blank"〉PubMed〈/a〉
    Keywords: Burial ; California ; Decision Making ; Female ; *Fossils ; Humans ; Indians, North American/*ethnology/*legislation & jurisprudence ; Male ; Museums ; Politics ; Seafood ; *Skeleton ; Universities/*legislation & jurisprudence
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  • 45
    Publication Date: 2008-11-11
    Description: Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3103772/" 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/PMC3103772/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stockmann, Christian -- Doedens, Andrew -- Weidemann, Alexander -- Zhang, Na -- Takeda, Norihiko -- Greenberg, Joshua I -- Cheresh, David A -- Johnson, Randall S -- AI060840/AI/NIAID NIH HHS/ -- CA118165/CA/NCI NIH HHS/ -- CA82515/CA/NCI NIH HHS/ -- R01 CA082515/CA/NCI NIH HHS/ -- R01 CA082515-12/CA/NCI NIH HHS/ -- R01 CA118165/CA/NCI NIH HHS/ -- England -- Nature. 2008 Dec 11;456(7223):814-8. doi: 10.1038/nature07445. Epub 2008 Nov 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Section, Division of Biological Sciences, Moores Cancer Center, University of California, San Diego, San Diego, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18997773" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anoxia/genetics ; Antineoplastic Agents, Alkylating/pharmacology ; Carcinoma/blood supply/genetics/*metabolism ; Cytotoxins/pharmacology ; Female ; *Gene Deletion ; Gene Expression Regulation, Neoplastic/drug effects ; Male ; Mammary Neoplasms, Experimental/blood supply/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells/*metabolism ; Neovascularization, Pathologic/metabolism ; Vascular Endothelial Growth Factor A/*genetics/*metabolism/pharmacology
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  • 46
    Publication Date: 2008-10-31
    Description: A long-standing issue in ecology is reconciling the apparent stability of many populations with robust predictions of large-amplitude population cycles from general theory on consumer-resource interactions. Even when consumers are decoupled from dynamic resources, large-amplitude cycles can theoretically emerge from delayed feedback processes found in many consumers. Here we show that resource-dependent mortality and a dynamic developmental delay in consumers produces a new type of small-amplitude cycle that coexists with large-amplitude fluctuations in coupled consumer-resource systems. A distinctive characteristic of the small-amplitude cycles is slow juvenile development for consumers, leading to a developmental delay that is longer than the cycle period. By contrast, the period exceeds the delay in large-amplitude cycles. These theoretical predictions may explain previous empirical results on coexisting attractors found in Daphnia-algal systems. To test this, we used bioassay experiments that measure the growth rates of individuals in populations exhibiting each type of cycle. The results were consistent with predictions. Together, the new theory and experiments establish that two very general features of consumers--a resource-dependent juvenile stage duration and resource-dependent mortality--combine to produce small-amplitude resource-consumer cycles. This phenomenon may contribute to the prevalence of small-amplitude fluctuations in many other consumer-resource populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCauley, Edward -- Nelson, William A -- Nisbet, Roger M -- England -- Nature. 2008 Oct 30;455(7217):1240-3. doi: 10.1038/nature07220.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolution Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada. mccauley@ucalgary.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18972019" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Assay ; Daphnia/growth & development/*physiology ; Eukaryota/*physiology ; Female ; *Food Chain ; Models, Biological ; Ovum/physiology
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  • 47
    Publication Date: 2008-06-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strasser, Hannes -- England -- Nature. 2008 Jun 26;453(7199):1177. doi: 10.1038/4531177c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18580923" target="_blank"〉PubMed〈/a〉
    Keywords: Cohort Studies ; Female ; Humans ; Randomized Controlled Trials as Topic/*ethics ; Stem Cell Transplantation/*ethics ; Urinary Incontinence/*therapy
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  • 48
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-01-04
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2742166/" 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/PMC2742166/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffith, Leslie C -- P01 NS044232/NS/NINDS NIH HHS/ -- P01 NS044232-070003/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Jan 3;451(7174):24-5. doi: 10.1038/451024a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172487" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/metabolism ; Copulation/*physiology ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/cytology/*physiology ; Female ; Genitalia, Female/metabolism ; Humans ; Male ; Mating Preference, Animal/*physiology ; Neurons/metabolism ; Peptides/metabolism
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  • 49
    Publication Date: 2008-10-04
    Description: Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682493/" 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/PMC3682493/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Worobey, Michael -- Gemmel, Marlea -- Teuwen, Dirk E -- Haselkorn, Tamara -- Kunstman, Kevin -- Bunce, Michael -- Muyembe, Jean-Jacques -- Kabongo, Jean-Marie M -- Kalengayi, Raphael M -- Van Marck, Eric -- Gilbert, M Thomas P -- Wolinsky, Steven M -- R21 AI065371/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):661-4. doi: 10.1038/nature07390.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ecology and Evolutionary Biology, University of Arizona, Tucson, Arizona 85721, USA. worobey@email.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833279" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Canada ; Democratic Republic of the Congo/epidemiology ; *Evolution, Molecular ; Female ; Genetic Variation/*genetics ; HIV Infections/*epidemiology/pathology/*virology ; HIV-1/classification/*genetics/*isolation & purification ; History, 20th Century ; Humans ; Male ; Microtomy ; Molecular Sequence Data ; Paraffin Embedding ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA
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  • 50
    Publication Date: 2008-07-03
    Description: Reprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4 (refs 1-11). Considering that ectopic expression of c-Myc causes tumorigenicity in offspring and that retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells. These two-factor iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimaeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jeong Beom -- Zaehres, Holm -- Wu, Guangming -- Gentile, Luca -- Ko, Kinarm -- Sebastiano, Vittorio -- Arauzo-Bravo, Marcos J -- Ruau, David -- Han, Dong Wook -- Zenke, Martin -- Scholer, Hans R -- England -- Nature. 2008 Jul 31;454(7204):646-50. doi: 10.1038/nature07061. Epub 2008 Jun 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Rontgenstrasse 20, 48149 Munster, NRW, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18594515" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology/metabolism ; Animals ; Cell Differentiation/genetics ; Cells, Cultured ; *Cellular Reprogramming ; Chimera ; DNA-Binding Proteins/genetics/metabolism ; Female ; Gene Expression Profiling ; Genes, myc/genetics ; HMGB Proteins/genetics/metabolism ; Homeodomain Proteins/genetics ; Kruppel-Like Transcription Factors/genetics/metabolism ; Male ; Mice ; Mice, Nude ; Mice, Transgenic ; Neurons/*cytology ; Octamer Transcription Factor-3/genetics/metabolism ; Pluripotent Stem Cells/*cytology/*metabolism ; Proteins/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; RNA, Untranslated ; SOXB1 Transcription Factors ; Transcription Factors/genetics/metabolism ; Transduction, Genetic
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  • 51
    Publication Date: 2008-05-30
    Description: Malaria parasites and related Apicomplexans are the causative agents of the some of the most serious infectious diseases of humans, companion animals, livestock and wildlife. These parasites must undergo sexual reproduction to transmit from vertebrate hosts to vectors, and their sex ratios are consistently female-biased. Sex allocation theory, a cornerstone of evolutionary biology, is remarkably successful at explaining female-biased sex ratios in multicellular taxa, but has proved controversial when applied to malaria parasites. Here we show that, as predicted by theory, sex ratio is an important fitness-determining trait and Plasmodium chabaudi parasites adjust their sex allocation in response to the presence of unrelated conspecifics. This suggests that P. chabaudi parasites use kin discrimination to evaluate the genetic diversity of their infections, and they adjust their behaviour in response to environmental cues. Malaria parasites provide a novel way to test evolutionary theory, and support the generality and power of a darwinian approach.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807728/" 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/PMC3807728/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reece, Sarah E -- Drew, Damien R -- Gardner, Andy -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 May 29;453(7195):609-14. doi: 10.1038/nature06954.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Evolutionary Biology, Ashworth Laboratories, School of Biological Science, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK. sarah.reece@ed.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509435" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Cues ; Female ; Fertility/genetics/physiology ; Genetic Variation ; Genotype ; Humans ; Malaria/*parasitology ; Male ; Models, Biological ; Plasmodium chabaudi/genetics/*physiology ; *Sex Ratio
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  • 52
    Publication Date: 2008-11-07
    Description: Intestinal homeostasis is critical for efficient energy extraction from food and protection from pathogens. Its disruption can lead to an array of severe illnesses with major impacts on public health, such as inflammatory bowel disease characterized by self-destructive intestinal immunity. However, the mechanisms regulating the equilibrium between the large bacterial flora and the immune system remain unclear. Intestinal lymphoid tissues generate flora-reactive IgA-producing B cells, and include Peyer's patches and mesenteric lymph nodes, as well as numerous isolated lymphoid follicles (ILFs). Here we show that peptidoglycan from Gram-negative bacteria is necessary and sufficient to induce the genesis of ILFs in mice through recognition by the NOD1 (nucleotide-binding oligomerization domain containing 1) innate receptor in epithelial cells, and beta-defensin 3- and CCL20-mediated signalling through the chemokine receptor CCR6. Maturation of ILFs into large B-cell clusters requires subsequent detection of bacteria by toll-like receptors. In the absence of ILFs, the composition of the intestinal bacterial community is profoundly altered. Our results demonstrate that intestinal bacterial commensals and the immune system communicate through an innate detection system to generate adaptive lymphoid tissues and maintain intestinal homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bouskra, Djahida -- Brezillon, Christophe -- Berard, Marion -- Werts, Catherine -- Varona, Rosa -- Boneca, Ivo Gomperts -- Eberl, Gerard -- England -- Nature. 2008 Nov 27;456(7221):507-10. doi: 10.1038/nature07450. Epub 2008 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur, Laboratory of Lymphoid Tissue Development, CNRS, URA1961.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18987631" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemokine CCL20/metabolism ; Chimera ; Female ; Germ-Free Life ; Gram-Negative Bacteria/genetics/immunology/isolation & purification/*physiology ; *Homeostasis ; Immunoglobulin A/immunology ; Intestines/immunology/*microbiology/*physiology ; Ligands ; Lymph Nodes/immunology ; Lymphoid Tissue/cytology/*immunology ; Male ; Mice ; Nod1 Signaling Adaptor Protein/deficiency/genetics/immunology/*metabolism ; Peptidoglycan/immunology ; Peyer's Patches/immunology ; Receptors, CCR6/deficiency/genetics/metabolism ; beta-Defensins/metabolism
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  • 53
    Publication Date: 2008-01-04
    Description: Epidemiological studies spanning more than 50 yr reach conflicting conclusions as to whether there is a lower incidence of solid tumours in people with trisomy 21 (Down's syndrome). We used mouse models of Down's syndrome and of cancer in a biological approach to investigate the relationship between trisomy and the incidence of intestinal tumours. Apc(Min)-mediated tumour number was determined in aneuploid mouse models Ts65Dn, Ts1Rhr and Ms1Rhr. Trisomy for orthologues of about half of the genes on chromosome 21 (Hsa21) in Ts65Dn mice or just 33 of these genes in Ts1Rhr mice resulted in a significant reduction in the number of intestinal tumours. In Ms1Rhr, segmental monosomy for the same 33 genes that are triplicated in Ts1Rhr resulted in an increased number of tumours. Further studies demonstrated that the Ets2 gene contributed most of the dosage-sensitive effect on intestinal tumour number. The action of Ets2 as a repressor when it is overexpressed differs from tumour suppression, which requires normal gene function to prevent cellular transformation. Upregulation of Ets2 and, potentially, other genes involved in this kind of protective effect may provide a prophylactic effect in all individuals, regardless of ploidy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sussan, Thomas E -- Yang, Annan -- Li, Fu -- Ostrowski, Michael C -- Reeves, Roger H -- R01 CA053271/CA/NCI NIH HHS/ -- England -- Nature. 2008 Jan 3;451(7174):73-5. doi: 10.1038/nature06446.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and The Institute for Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172498" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Chromosomes, Mammalian/genetics ; *Disease Models, Animal ; Down Syndrome/*complications/*genetics/pathology ; Female ; Gene Dosage ; Genes, APC/*physiology ; Intestinal Neoplasms/complications/*genetics/pathology/*prevention & control ; Male ; Mice ; Proto-Oncogene Protein c-ets-2/genetics/metabolism ; Trisomy/*genetics
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  • 54
    Publication Date: 2008-07-04
    Description: Extinction risk in natural populations depends on stochastic factors that affect individuals, and is estimated by incorporating such factors into stochastic models. Stochasticity can be divided into four categories, which include the probabilistic nature of birth and death at the level of individuals (demographic stochasticity), variation in population-level birth and death rates among times or locations (environmental stochasticity), the sex of individuals and variation in vital rates among individuals within a population (demographic heterogeneity). Mechanistic stochastic models that include all of these factors have not previously been developed to examine their combined effects on extinction risk. Here we derive a family of stochastic Ricker models using different combinations of all these stochastic factors, and show that extinction risk depends strongly on the combination of factors that contribute to stochasticity. Furthermore, we show that only with the full stochastic model can the relative importance of environmental and demographic variability, and therefore extinction risk, be correctly determined. Using the full model, we find that demographic sources of stochasticity are the prominent cause of variability in a laboratory population of Tribolium castaneum (red flour beetle), whereas using only the standard simpler models would lead to the erroneous conclusion that environmental variability dominates. Our results demonstrate that current estimates of extinction risk for natural populations could be greatly underestimated because variability has been mistakenly attributed to the environment rather than the demographic factors described here that entail much higher extinction risk for the same variability level.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Melbourne, Brett A -- Hastings, Alan -- England -- Nature. 2008 Jul 3;454(7200):100-3. doi: 10.1038/nature06922.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Colorado, Boulder, Colorado 80309, USA. brett.melbourne@colorado.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18596809" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Environment ; *Extinction, Biological ; Female ; Fishes ; Life Cycle Stages ; Male ; Models, Statistical ; Risk Factors ; Stochastic Processes ; Tribolium/*physiology
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  • 55
    Publication Date: 2008-08-30
    Description: Sensory hair cells in the mammalian cochlea convert mechanical stimuli into electrical impulses that subserve audition. Loss of hair cells and their innervating neurons is the most frequent cause of hearing impairment. Atonal homologue 1 (encoded by Atoh1, also known as Math1) is a basic helix-loop-helix transcription factor required for hair-cell development, and its misexpression in vitro and in vivo generates hair-cell-like cells. Atoh1-based gene therapy to ameliorate auditory and vestibular dysfunction has been proposed. However, the biophysical properties of putative hair cells induced by Atoh1 misexpression have not been characterized. Here we show that in utero gene transfer of Atoh1 produces functional supernumerary hair cells in the mouse cochlea. The induced hair cells display stereociliary bundles, attract neuronal processes and express the ribbon synapse marker carboxy-terminal binding protein 2 (refs 12,13). Moreover, the hair cells are capable of mechanoelectrical transduction and show basolateral conductances with age-appropriate specializations. Our results demonstrate that manipulation of cell fate by transcription factor misexpression produces functional sensory cells in the postnatal mammalian cochlea. We expect that our in utero gene transfer paradigm will enable the design and validation of gene therapies to ameliorate hearing loss in mouse models of human deafness.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925035/" 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/PMC2925035/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gubbels, Samuel P -- Woessner, David W -- Mitchell, John C -- Ricci, Anthony J -- Brigande, John V -- R01 DC008595/DC/NIDCD NIH HHS/ -- R01 DC008595-03/DC/NIDCD NIH HHS/ -- England -- Nature. 2008 Sep 25;455(7212):537-41. doi: 10.1038/nature07265. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Otolaryngology, Oregon Hearing Research Center, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics/*metabolism ; Cochlea/*cytology/embryology/growth & development/innervation/*metabolism ; Deafness/genetics/therapy ; Disease Models, Animal ; Dyneins/metabolism ; Electric Conductivity ; Female ; Genetic Therapy ; Hair Cells, Auditory/cytology/*physiology ; Humans ; Mechanotransduction, Cellular ; Mice ; Myosins/metabolism ; Pregnancy ; Synapses/metabolism ; *Transfection ; *Uterus
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  • 56
    Publication Date: 2008-10-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirkpatrick, Mark -- Price, Trevor -- England -- Nature. 2008 Oct 2;455(7213):601-2. doi: 10.1038/455601a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18833264" target="_blank"〉PubMed〈/a〉
    Keywords: Africa, Eastern ; Animals ; Biodiversity ; Cichlids/classification/*genetics/*physiology ; Color ; Female ; Fish Proteins/genetics/metabolism ; Fresh Water ; *Genetic Speciation ; Male ; Mating Preference, Animal/*physiology ; Phenotype ; Pigmentation/genetics/*physiology ; Reproduction/physiology ; Rod Opsins/genetics/metabolism
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  • 57
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-10-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirkwood, Thomas B L -- England -- Nature. 2008 Oct 9;455(7214):739-40. doi: 10.1038/455739a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18843351" target="_blank"〉PubMed〈/a〉
    Keywords: Aged, 80 and over ; Aging/*physiology ; Cross-Sectional Studies ; Denmark ; Disabled Persons/statistics & numerical data ; Female ; *Health ; Health Care Costs/statistics & numerical data ; Humans ; Life Expectancy/ethnology/trends ; Longevity/*physiology ; Longitudinal Studies ; Male ; *Quality of Life ; Sex Characteristics
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  • 58
    Publication Date: 2008-06-13
    Description: Osteoclasts are multinucleated haematopoietic cells that resorb bone. Increased osteoclast activity causes osteoporosis, a disorder resulting in a low bone mass and a high risk of fractures. Increased osteoclast size and numbers are also a hallmark of other disorders, such as Paget's disease and multiple myeloma. The protein c-Fos, a component of the AP-1 transcription factor complex, is essential for osteoclast differentiation. Here we show that the Fos-related protein Fra-2 controls osteoclast survival and size. The bones of Fra-2-deficient newborn mice have giant osteoclasts, and signalling through leukaemia inhibitory factor (LIF) and its receptor is impaired. Similarly, newborn animals lacking LIF have giant osteoclasts, and we show that LIF is a direct transcriptional target of Fra-2 and c-Jun. Moreover, bones deficient in Fra-2 and LIF are hypoxic and express increased levels of hypoxia-induced factor 1alpha (HIF1alpha) and Bcl-2. Overexpression of Bcl-2 is sufficient to induce giant osteoclasts in vivo, whereas Fra-2 and LIF affect HIF1alpha through transcriptional modulation of the HIF prolyl hydroxylase PHD2. This pathway is operative in the placenta, because specific inactivation of Fra-2 in the embryo alone does not cause hypoxia or the giant osteoclast phenotype. Thus placenta-induced hypoxia during embryogenesis leads to the formation of giant osteoclasts in young pups. These findings offer potential targets for the treatment of syndromes associated with increased osteoclastogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bozec, Aline -- Bakiri, Latifa -- Hoebertz, Astrid -- Eferl, Robert -- Schilling, Arndt F -- Komnenovic, Vukoslav -- Scheuch, Harald -- Priemel, Matthias -- Stewart, Colin L -- Amling, Michael -- Wagner, Erwin F -- England -- Nature. 2008 Jul 10;454(7201):221-5. doi: 10.1038/nature07019. Epub 2008 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (I.M.P.), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548006" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Anoxia/*metabolism/pathology ; Bone and Bones/cytology/metabolism/pathology ; *Cell Size ; Cell Survival ; DNA-Binding Proteins/metabolism ; Female ; Fos-Related Antigen-2/deficiency/genetics/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; Immediate-Early Proteins/metabolism ; Leukemia Inhibitory Factor/deficiency/genetics/*metabolism ; Leukemia Inhibitory Factor Receptor alpha Subunit/*metabolism ; Male ; Mice ; Osteoclasts/*cytology/metabolism/pathology ; Procollagen-Proline Dioxygenase ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2 ; *Signal Transduction
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  • 59
    Publication Date: 2008-02-29
    Description: Courtship is an innate sexually dimorphic behaviour that can be observed in naive animals without previous learning or experience, suggesting that the neural circuits that mediate this behaviour are developmentally programmed. In Drosophila, courtship involves a complex yet stereotyped array of dimorphic behaviours that are regulated by Fru(M), a male-specific isoform of the fruitless gene. Fru(M) is expressed in about 2,000 neurons in the fly brain, including three subpopulations of olfactory sensory neurons and projection neurons (PNs). One set of Fru(+) olfactory neurons expresses the odorant receptor Or67d and responds to the male-specific pheromone cis-vaccenyl acetate (cVA). These neurons converge on the DA1 glomerulus in the antennal lobe. In males, activation of Or67d(+) neurons by cVA inhibits courtship of other males, whereas in females their activation promotes receptivity to other males. These observations pose the question of how a single pheromone acting through the same set of sensory neurons can elicit different behaviours in male and female flies. Anatomical or functional dimorphisms in this neural circuit might be responsible for the dimorphic behaviour. We therefore developed a neural tracing procedure that employs two-photon laser scanning microscopy to activate the photoactivatable green fluorescent protein. Here we show, using this technique, that the projections from the DA1 glomerulus to the protocerebrum are sexually dimorphic. We observe a male-specific axonal arbor in the lateral horn whose elaboration requires the expression of the transcription factor Fru(M) in DA1 projection neurons and other Fru(+) cells. The observation that cVA activates a sexually dimorphic circuit in the protocerebrum suggests a mechanism by which a single pheromone can elicit different behaviours in males and in females.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Datta, Sandeep Robert -- Vasconcelos, Maria Luisa -- Ruta, Vanessa -- Luo, Sean -- Wong, Allan -- Demir, Ebru -- Flores, Jorge -- Balonze, Karen -- Dickson, Barry J -- Axel, Richard -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 27;452(7186):473-7. doi: 10.1038/nature06808. Epub 2008 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18305480" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/*pharmacology ; Animals ; Courtship ; Drosophila/cytology/*drug effects/*physiology ; Drosophila Proteins/deficiency/genetics/metabolism ; Female ; Male ; Nerve Tissue Proteins/deficiency/genetics/metabolism ; Neural Pathways/*drug effects ; Neurons/drug effects/physiology ; Oleic Acids/*pharmacology ; Pheromones/*pharmacology ; Protein Isoforms/genetics/metabolism ; *Sex Characteristics ; Sexual Behavior, Animal/*drug effects/physiology ; Smell/drug effects/physiology ; Transcription Factors/deficiency/genetics/metabolism
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  • 60
    Publication Date: 2008-05-09
    Description: Cancer stem cells, which share many common properties and regulatory machineries with normal stem cells, have recently been proposed to be responsible for tumorigenesis and to contribute to cancer resistance. The main challenges in cancer biology are to identify cancer stem cells and to define the molecular events required for transforming normal cells to cancer stem cells. Here we show that Pten deletion in mouse haematopoietic stem cells leads to a myeloproliferative disorder, followed by acute T-lymphoblastic leukaemia (T-ALL). Self-renewable leukaemia stem cells (LSCs) are enriched in the c-Kit(mid)CD3(+)Lin(-) compartment, where unphosphorylated beta-catenin is significantly increased. Conditional ablation of one allele of the beta-catenin gene substantially decreases the incidence and delays the occurrence of T-ALL caused by Pten loss, indicating that activation of the beta-catenin pathway may contribute to the formation or expansion of the LSC population. Moreover, a recurring chromosomal translocation, T(14;15), results in aberrant overexpression of the c-myc oncogene in c-Kit(mid)CD3(+)Lin(-) LSCs and CD3(+) leukaemic blasts, recapitulating a subset of human T-ALL. No alterations in Notch1 signalling are detected in this model, suggesting that Pten inactivation and c-myc overexpression may substitute functionally for Notch1 abnormalities, leading to T-ALL development. Our study indicates that multiple genetic or molecular alterations contribute cooperatively to LSC transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840044/" 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/PMC2840044/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Wei -- Lasky, Joseph L -- Chang, Chun-Ju -- Mosessian, Sherly -- Lewis, Xiaoman -- Xiao, Yun -- Yeh, Jennifer E -- Chen, James Y -- Iruela-Arispe, M Luisa -- Varella-Garcia, Marileila -- Wu, Hong -- CA16042/CA/NCI NIH HHS/ -- R01 CA121110/CA/NCI NIH HHS/ -- R01 CA121110-01A1/CA/NCI NIH HHS/ -- England -- Nature. 2008 May 22;453(7194):529-33. doi: 10.1038/nature06933. Epub 2008 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18463637" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD3/metabolism ; Cell Proliferation ; Chromosomes, Mammalian/genetics ; Female ; Hematopoietic Stem Cells/cytology/pathology ; In Situ Hybridization, Fluorescence ; Leukemia-Lymphoma, Adult T-Cell/*pathology ; Male ; Mice ; Neoplastic Stem Cells/*metabolism/*pathology ; PTEN Phosphohydrolase/*deficiency/*genetics ; Proto-Oncogene Proteins c-kit/metabolism ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Receptors, Antigen, T-Cell/genetics ; Translocation, Genetic ; beta Catenin/metabolism
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  • 61
    Publication Date: 2008-04-12
    Description: Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways. Here we show that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endo-siRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endo-siRNA targets, demonstrating their regulatory activity. Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute-mediated catalysis in mammals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981145/" 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/PMC2981145/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tam, Oliver H -- Aravin, Alexei A -- Stein, Paula -- Girard, Angelique -- Murchison, Elizabeth P -- Cheloufi, Sihem -- Hodges, Emily -- Anger, Martin -- Sachidanandam, Ravi -- Schultz, Richard M -- Hannon, Gregory J -- P01 CA013106-34/CA/NCI NIH HHS/ -- R01 GM062534/GM/NIGMS NIH HHS/ -- R01 GM062534-07/GM/NIGMS NIH HHS/ -- R01 GM062534-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 May 22;453(7194):534-8. doi: 10.1038/nature06904. Epub 2008 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18404147" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computational Biology ; DNA Transposable Elements/genetics ; Female ; Gene Expression Regulation, Developmental ; Gene Library ; Mice ; Oocytes/*metabolism ; Pseudogenes/*genetics ; *RNA Interference ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/*genetics ; Ribonuclease III/deficiency/genetics/metabolism
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  • 62
    Publication Date: 2008-07-03
    Description: Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tammela, Tuomas -- Zarkada, Georgia -- Wallgard, Elisabet -- Murtomaki, Aino -- Suchting, Steven -- Wirzenius, Maria -- Waltari, Marika -- Hellstrom, Mats -- Schomber, Tibor -- Peltonen, Reetta -- Freitas, Catarina -- Duarte, Antonio -- Isoniemi, Helena -- Laakkonen, Pirjo -- Christofori, Gerhard -- Yla-Herttuala, Seppo -- Shibuya, Masabumi -- Pytowski, Bronislaw -- Eichmann, Anne -- Betsholtz, Christer -- Alitalo, Kari -- 5 R01 HL075183-02/HL/NHLBI NIH HHS/ -- England -- Nature. 2008 Jul 31;454(7204):656-60. doi: 10.1038/nature07083. Epub 2008 Jun 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and the Haartman Institute University of Helsinki, PO Box 63 (Haartmaninkatu 8), 00014 Helsinki, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18594512" target="_blank"〉PubMed〈/a〉
    Keywords: Angiogenesis Inhibitors/pharmacology ; Animals ; Antibodies, Monoclonal/pharmacology ; Cell Line, Tumor ; Dipeptides/pharmacology ; Down-Regulation ; Endothelial Cells/metabolism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Ligands ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Neoplasms/*blood supply/drug therapy ; Neovascularization, Pathologic/genetics/*metabolism ; Receptors, Notch/metabolism ; Signal Transduction ; Vascular Endothelial Growth Factor Receptor-3/*antagonists & ; inhibitors/*metabolism
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  • 63
    Publication Date: 2008-05-20
    Description: Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of human diseases. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10-15 years of the onset of the symptoms. HD is caused by the expansion of cytosine-adenine-guanine (CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin (HTT) gene. Mutant HTT with expanded polyglutamine (polyQ) is widely expressed in the brain and peripheral tissues, but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological, neurological and genetic similarities between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases. Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine-expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652570/" 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/PMC2652570/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Shang-Hsun -- Cheng, Pei-Hsun -- Banta, Heather -- Piotrowska-Nitsche, Karolina -- Yang, Jin-Jing -- Cheng, Eric C H -- Snyder, Brooke -- Larkin, Katherine -- Liu, Jun -- Orkin, Jack -- Fang, Zhi-Hui -- Smith, Yoland -- Bachevalier, Jocelyne -- Zola, Stuart M -- Li, Shi-Hua -- Li, Xiao-Jiang -- Chan, Anthony W S -- R01 AG019206/AG/NIA NIH HHS/ -- R01 AG019206-07/AG/NIA NIH HHS/ -- R01 NS036232/NS/NINDS NIH HHS/ -- R01 NS036232-09/NS/NINDS NIH HHS/ -- R01 NS041669/NS/NINDS NIH HHS/ -- R01 NS041669-07/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Jun 12;453(7197):921-4. doi: 10.1038/nature06975. Epub 2008 May 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18488016" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Animals, Newborn ; Brain/metabolism/pathology ; Chorea/genetics/physiopathology ; *Disease Models, Animal ; Dystonia/genetics/physiopathology ; Exons/genetics ; Female ; Humans ; Huntington Disease/*genetics/metabolism/pathology/*physiopathology ; Macaca mulatta/*genetics ; Male ; Nerve Tissue Proteins/*genetics/metabolism ; Nuclear Proteins/*genetics/metabolism ; Peptides/genetics/metabolism ; Pregnancy ; Survival Analysis ; Trinucleotide Repeat Expansion/*genetics
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  • 64
    Publication Date: 2007
    Description: Mating in many species induces a dramatic switch in female reproductive behaviour. In most insects, this switch is triggered by factors present in the male's seminal fluid. How these factors exert such profound effects in females is unknown. Here we identify a receptor for the Drosophila melanogaster sex peptide (SP, also known as Acp70A), the primary trigger of post-mating responses in this species. Females that lack the sex peptide receptor (SPR, also known as CG16752), either entirely or only in the nervous system, fail to respond to SP and continue to show virgin behaviours even after mating. SPR is expressed in the female's reproductive tract and central nervous system. The behavioural functions of SPR map to the subset of neurons that also express the fruitless gene, a key determinant of sex-specific reproductive behaviour. SPR is highly conserved across insects, opening up the prospect of new strategies to control the reproductive and host-seeking behaviours of agricultural pests and human disease vectors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yapici, Nilay -- Kim, Young-Joon -- Ribeiro, Carlos -- Dickson, Barry J -- England -- Nature. 2008 Jan 3;451(7174):33-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18066048" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/metabolism ; Conserved Sequence ; Copulation/physiology ; Drosophila Proteins/chemistry/deficiency/genetics/*metabolism ; Drosophila melanogaster/cytology/*physiology ; Female ; Genitalia, Female/metabolism ; Male ; Nerve Tissue Proteins/metabolism ; Neurons/metabolism ; Peptides/chemistry/deficiency/genetics/*metabolism ; Sexual Behavior, Animal/*physiology ; Substrate Specificity ; Transcription Factors/metabolism
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  • 65
    Publication Date: 2008-08-30
    Description: Ligand-dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues. Here we show that, although previous reports have described a cell-autonomous role for Hh signalling in these tumours, Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand-dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti-Hh antibody or genetic deletion of smoothened (Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh-expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yauch, Robert L -- Gould, Stephen E -- Scales, Suzie J -- Tang, Tracy -- Tian, Hua -- Ahn, Christina P -- Marshall, Derek -- Fu, Ling -- Januario, Thomas -- Kallop, Dara -- Nannini-Pepe, Michelle -- Kotkow, Karen -- Marsters, James C -- Rubin, Lee L -- de Sauvage, Frederic J -- England -- Nature. 2008 Sep 18;455(7211):406-10. doi: 10.1038/nature07275. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Hedgehog Proteins/*metabolism ; Humans ; Ligands ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms/genetics/*metabolism ; Paracrine Communication/*physiology ; Receptors, G-Protein-Coupled/deficiency/genetics/metabolism ; Stromal Cells/*metabolism
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  • 66
    Publication Date: 2008-09-09
    Description: Human mathematical competence emerges from two representational systems. Competence in some domains of mathematics, such as calculus, relies on symbolic representations that are unique to humans who have undergone explicit teaching. More basic numerical intuitions are supported by an evolutionarily ancient approximate number system that is shared by adults, infants and non-human animals-these groups can all represent the approximate number of items in visual or auditory arrays without verbally counting, and use this capacity to guide everyday behaviour such as foraging. Despite the widespread nature of the approximate number system both across species and across development, it is not known whether some individuals have a more precise non-verbal 'number sense' than others. Furthermore, the extent to which this system interfaces with the formal, symbolic maths abilities that humans acquire by explicit instruction remains unknown. Here we show that there are large individual differences in the non-verbal approximation abilities of 14-year-old children, and that these individual differences in the present correlate with children's past scores on standardized maths achievement tests, extending all the way back to kindergarten. Moreover, this correlation remains significant when controlling for individual differences in other cognitive and performance factors. Our results show that individual differences in achievement in school mathematics are related to individual differences in the acuity of an evolutionarily ancient, unlearned approximate number sense. Further research will determine whether early differences in number sense acuity affect later maths learning, whether maths education enhances number sense acuity, and the extent to which tertiary factors can affect both.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halberda, Justin -- Mazzocco, Michele M M -- Feigenson, Lisa -- R01 HD 034061/HD/NICHD NIH HHS/ -- R01 HD034061/HD/NICHD NIH HHS/ -- England -- Nature. 2008 Oct 2;455(7213):665-8. doi: 10.1038/nature07246. Epub 2008 Sep 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University, Ames Hall, 3400 North Charles Street, Baltimore, Maryland 21218, USA. halberda@jhu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18776888" target="_blank"〉PubMed〈/a〉
    Keywords: *Achievement ; Adolescent ; Biological Evolution ; Child ; Child, Preschool ; Cognition/*physiology ; Education ; Female ; Humans ; *Individuality ; Linear Models ; Longitudinal Studies ; Male ; *Mathematics ; Schools
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2008-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yeager, Ashley -- England -- Nature. 2008 Oct 30;455(7217):1154-5. doi: 10.1038/4551154a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971982" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Embryo Research/economics/*legislation & jurisprudence ; *Embryonic Stem Cells/cytology ; *Federal Government ; Female ; Humans ; Michigan ; *State Government
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  • 68
    Publication Date: 2008-11-21
    Description: In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, and studies to date have typically focused on short mitochondrial sequences, never yielding more than a fraction of a per cent of any nuclear genome. Here we describe 4.17 billion bases (Gb) of sequence from several mammoth specimens, 3.3 billion (80%) of which are from the woolly mammoth (Mammuthus primigenius) genome and thus comprise an extensive set of genome-wide sequence from an extinct species. Our data support earlier reports that elephantid genomes exceed 4 Gb. The estimated divergence rate between mammoth and African elephant is half of that between human and chimpanzee. The observed number of nucleotide differences between two particular mammoths was approximately one-eighth of that between one of them and the African elephant, corresponding to a separation between the mammoths of 1.5-2.0 Myr. The estimated probability that orthologous elephant and mammoth amino acids differ is 0.002, corresponding to about one residue per protein. Differences were discovered between mammoth and African elephant in amino-acid positions that are otherwise invariant over several billion years of combined mammalian evolution. This study shows that nuclear genome sequencing of extinct species can reveal population differences not evident from the fossil record, and perhaps even discover genetic factors that affect extinction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Webb -- Drautz, Daniela I -- Ratan, Aakrosh -- Pusey, Barbara -- Qi, Ji -- Lesk, Arthur M -- Tomsho, Lynn P -- Packard, Michael D -- Zhao, Fangqing -- Sher, Andrei -- Tikhonov, Alexei -- Raney, Brian -- Patterson, Nick -- Lindblad-Toh, Kerstin -- Lander, Eric S -- Knight, James R -- Irzyk, Gerard P -- Fredrikson, Karin M -- Harkins, Timothy T -- Sheridan, Sharon -- Pringle, Tom -- Schuster, Stephan C -- HG002238/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Nov 20;456(7220):387-90. doi: 10.1038/nature07446.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pennsylvania State University, Center for Comparative Genomics and Bioinformatics, 310 Wartik Building, University Park, Pennsylvania 16802, USA. webb@bx.psu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19020620" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; Cell Nucleus/*genetics ; Conserved Sequence/genetics ; Elephants/anatomy & histology/*genetics ; *Evolution, Molecular ; *Extinction, Biological ; Female ; *Fossils ; Genome/*genetics ; *Genomics ; Hair/metabolism ; Humans ; India ; Male ; Phylogeny ; Sequence Analysis, DNA/*methods
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  • 69
    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, Susan -- England -- Nature. 2008 May 8;453(7192):138-9. doi: 10.1038/453138a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18464700" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; Birds/genetics ; *Evolution, Molecular ; Female ; Genome/*genetics ; Male ; Mammals/genetics ; Milk ; *Phylogeny ; Platypus/classification/*genetics/physiology ; Reptiles/genetics ; Sex Chromosomes/genetics ; Vitellogenins/genetics ; Zona Pellucida
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  • 70
    Publication Date: 2008-03-14
    Description: The autosomal dominant hyper-IgE syndrome (HIES, 'Job's syndrome') is characterized by recurrent and often severe pulmonary infections, pneumatoceles, eczema, staphylococcal abscesses, mucocutaneous candidiasis, and abnormalities of bone and connective tissue. Mutations presumed to underlie HIES have recently been identified in stat3, the gene encoding STAT3 (signal transducer and activator of transcription 3) (refs 3, 4). Although impaired production of interferon-gamma and tumour-necrosis factor by T cells, diminished memory T-cell populations, decreased delayed-type-hypersensitivity responses and decreased in vitro lymphoproliferation in response to specific antigens have variably been described, specific immunological abnormalities that can explain the unique susceptibility to particular infections seen in HIES have not yet been defined. Here we show that interleukin (IL)-17 production by T cells is absent in HIES individuals. We observed that ex vivo T cells from subjects with HIES failed to produce IL-17, but not IL-2, tumour-necrosis factor or interferon-gamma, on mitogenic stimulation with staphylococcal enterotoxin B or on antigenic stimulation with Candida albicans or streptokinase. Purified naive T cells were unable to differentiate into IL-17-producing (T(H)17) T helper cells in vitro and had lower expression of retinoid-related orphan receptor (ROR)-gammat, which is consistent with a crucial role for STAT3 signalling in the generation of T(H)17 cells. T(H)17 cells have emerged as an important subset of helper T cells that are believed to be critical in the clearance of fungal and extracellular bacterial infections. Thus, our data suggest that the inability to produce T(H)17 cells is a mechanism underlying the susceptibility to the recurrent infections commonly seen in HIES.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864108/" 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/PMC2864108/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Milner, Joshua D -- Brenchley, Jason M -- Laurence, Arian -- Freeman, Alexandra F -- Hill, Brenna J -- Elias, Kevin M -- Kanno, Yuka -- Spalding, Christine -- Elloumi, Houda Z -- Paulson, Michelle L -- Davis, Joie -- Hsu, Amy -- Asher, Ava I -- O'Shea, John -- Holland, Steven M -- Paul, William E -- Douek, Daniel C -- Z99 AI999999/Intramural NIH HHS/ -- England -- Nature. 2008 Apr 10;452(7188):773-6. doi: 10.1038/nature06764. Epub 2008 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, 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/18337720" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Candida albicans/immunology ; *Cell Differentiation ; Child ; Child, Preschool ; Enterotoxins/immunology ; Female ; *Genes, Dominant ; Humans ; Interferon-gamma/biosynthesis/immunology ; Interleukin-17/*biosynthesis ; Interleukin-2/biosynthesis/immunology ; Job Syndrome/genetics/*immunology/metabolism/*pathology ; Male ; Middle Aged ; Streptokinase/metabolism ; T-Lymphocytes, Helper-Inducer/immunology/*metabolism/*pathology ; Tumor Necrosis Factor-alpha/biosynthesis/immunology
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  • 71
    Publication Date: 2008-06-13
    Description: Animals from flies to humans are able to distinguish subtle gradations in temperature and show strong temperature preferences. Animals move to environments of optimal temperature and some manipulate the temperature of their surroundings, as humans do using clothing and shelter. Despite the ubiquitous influence of environmental temperature on animal behaviour, the neural circuits and strategies through which animals select a preferred temperature remain largely unknown. Here we identify a small set of warmth-activated anterior cell (AC) neurons located in the Drosophila brain, the function of which is critical for preferred temperature selection. AC neuron activation occurs just above the fly's preferred temperature and depends on dTrpA1, an ion channel that functions as a molecular sensor of warmth. Flies that selectively express dTrpA1 in the AC neurons select normal temperatures, whereas flies in which dTrpA1 function is reduced or eliminated choose warmer temperatures. This internal warmth-sensing pathway promotes avoidance of slightly elevated temperatures and acts together with a distinct pathway for cold avoidance to set the fly's preferred temperature. Thus, flies select a preferred temperature by using a thermal sensing pathway tuned to trigger avoidance of temperatures that deviate even slightly from the preferred temperature. This provides a potentially general strategy for robustly selecting a narrow temperature range optimal for survival.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730888/" 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/PMC2730888/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamada, Fumika N -- Rosenzweig, Mark -- Kang, Kyeongjin -- Pulver, Stefan R -- Ghezzi, Alfredo -- Jegla, Timothy J -- Garrity, Paul A -- P01 NS044232/NS/NINDS NIH HHS/ -- P01 NS044232-060002/NS/NINDS NIH HHS/ -- P01 NS044232-070002/NS/NINDS NIH HHS/ -- P30 NS045713/NS/NINDS NIH HHS/ -- P30 NS045713-069006/NS/NINDS NIH HHS/ -- P30 NS045713S10/NS/NINDS NIH HHS/ -- R01 EY013874/EY/NEI NIH HHS/ -- R01 EY013874-06/EY/NEI NIH HHS/ -- R01 EY13874/EY/NEI NIH HHS/ -- R01 MH067284/MH/NIMH NIH HHS/ -- R01 MH067284-05/MH/NIMH NIH HHS/ -- RR16780/RR/NCRR NIH HHS/ -- England -- Nature. 2008 Jul 10;454(7201):217-20. doi: 10.1038/nature07001. Epub 2008 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Behavioral Genomics, Volen Center for Complex Systems, Biology Department, Brandeis University MS-008, 415 South Street, Waltham, Massachusetts 02454, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548007" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avoidance Learning ; Body Temperature ; Choice Behavior/*physiology ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/growth & development/*physiology ; Female ; Larva ; Molecular Sequence Data ; Neurons/metabolism ; Oocytes/metabolism ; TRPC Cation Channels/genetics/*metabolism ; *Temperature ; Xenopus laevis
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  • 72
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Apr 24;452(7190):913. doi: 10.1038/452913a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18432217" target="_blank"〉PubMed〈/a〉
    Keywords: Embryo Research/*ethics/legislation & jurisprudence ; Female ; Humans ; Male ; Ovum/*cytology ; Pluripotent Stem Cells/*cytology ; Pregnancy ; Skin/cytology ; Spermatozoa/*cytology
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  • 73
    Publication Date: 2008-04-18
    Description: The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture. Constant vessel remodelling leads to spontaneous haemorrhages and increased interstitial fluid pressure in the tumour environment. Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma. The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamzah, Juliana -- Jugold, Manfred -- Kiessling, Fabian -- Rigby, Paul -- Manzur, Mitali -- Marti, Hugo H -- Rabie, Tamer -- Kaden, Sylvia -- Grone, Hermann-Josef -- Hammerling, Gunter J -- Arnold, Bernd -- Ganss, Ruth -- England -- Nature. 2008 May 15;453(7193):410-4. doi: 10.1038/nature06868. Epub 2008 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Western Australian Institute for Medical Research, UWA Centre for Medical Research, Perth, Western Australia 6000, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18418378" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capillary Permeability ; Cell Hypoxia/physiology ; Female ; Male ; Mice ; Neovascularization, Pathologic/*prevention & control ; Oxygen/metabolism ; Pancreatic Neoplasms/*blood supply/genetics/*immunology/metabolism ; RGS Proteins/*deficiency/genetics/*metabolism
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  • 74
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    Publication Date: 2008-05-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Jai Y -- Dickson, Barry J -- England -- Nature. 2008 May 1;453(7191):41-2. doi: 10.1038/453041a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451846" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Communication ; Animals ; Courtship ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/genetics/*physiology/radiation effects ; Female ; Male ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/metabolism/radiation effects ; Psychomotor Performance/physiology/radiation effects ; *Sex Characteristics ; Transcription Factors/genetics/metabolism ; Vibration ; Wings, Animal/physiology/radiation effects
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  • 75
    Publication Date: 2008-02-19
    Description: Understanding the neuropathology of multiple sclerosis (MS) is essential for improved therapies. Therefore, identification of targets specific to pathological types of MS may have therapeutic benefits. Here we identify, by laser-capture microdissection and proteomics, proteins unique to three major types of MS lesions: acute plaque, chronic active plaque and chronic plaque. Comparative proteomic profiles identified tissue factor and protein C inhibitor within chronic active plaque samples, suggesting dysregulation of molecules associated with coagulation. In vivo administration of hirudin or recombinant activated protein C reduced disease severity in experimental autoimmune encephalomyelitis and suppressed Th1 and Th17 cytokines in astrocytes and immune cells. Administration of mutant forms of recombinant activated protein C showed that both its anticoagulant and its signalling functions were essential for optimal amelioration of experimental autoimmune encephalomyelitis. A proteomic approach illuminated potential therapeutic targets selective for specific pathological stages of MS and implicated participation of the coagulation cascade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, May H -- Hwang, Sun-Il -- Roy, Dolly B -- Lundgren, Deborah H -- Price, Jordan V -- Ousman, Shalina S -- Fernald, Guy Haskin -- Gerlitz, Bruce -- Robinson, William H -- Baranzini, Sergio E -- Grinnell, Brian W -- Raine, Cedric S -- Sobel, Raymond A -- Han, David K -- Steinman, Lawrence -- T32 AI007290/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Feb 28;451(7182):1076-81. doi: 10.1038/nature06559. Epub 2008 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, 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/18278032" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Blood Coagulation ; Encephalomyelitis, Autoimmune, Experimental/immunology/metabolism/pathology ; Female ; *Gene Expression Profiling ; Humans ; Inflammation/metabolism/pathology ; Male ; Mice ; Middle Aged ; Multiple Sclerosis/classification/drug therapy/*metabolism/*pathology ; Protein C/genetics/metabolism/pharmacology ; *Proteomics ; Th1 Cells/immunology ; Th2 Cells/immunology ; Thrombin/antagonists & inhibitors/metabolism
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  • 76
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    Publication Date: 2008-04-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Apr 10;452(7188):665-6. doi: 10.1038/452665b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18401358" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Enhancement/*ethics ; Female ; Humans ; Pregnancy ; *Public Opinion ; Transsexualism/*psychology
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  • 77
    Publication Date: 2008-04-04
    Description: Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539558/" 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/PMC4539558/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thorgeirsson, Thorgeir E -- Geller, Frank -- Sulem, Patrick -- Rafnar, Thorunn -- Wiste, Anna -- Magnusson, Kristinn P -- Manolescu, Andrei -- Thorleifsson, Gudmar -- Stefansson, Hreinn -- Ingason, Andres -- Stacey, Simon N -- Bergthorsson, Jon T -- Thorlacius, Steinunn -- Gudmundsson, Julius -- Jonsson, Thorlakur -- Jakobsdottir, Margret -- Saemundsdottir, Jona -- Olafsdottir, Olof -- Gudmundsson, Larus J -- Bjornsdottir, Gyda -- Kristjansson, Kristleifur -- Skuladottir, Halla -- Isaksson, Helgi J -- Gudbjartsson, Tomas -- Jones, Gregory T -- Mueller, Thomas -- Gottsater, Anders -- Flex, Andrea -- Aben, Katja K H -- de Vegt, Femmie -- Mulders, Peter F A -- Isla, Dolores -- Vidal, Maria J -- Asin, Laura -- Saez, Berta -- Murillo, Laura -- Blondal, Thorsteinn -- Kolbeinsson, Halldor -- Stefansson, Jon G -- Hansdottir, Ingunn -- Runarsdottir, Valgerdur -- Pola, Roberto -- Lindblad, Bengt -- van Rij, Andre M -- Dieplinger, Benjamin -- Haltmayer, Meinhard -- Mayordomo, Jose I -- Kiemeney, Lambertus A -- Matthiasson, Stefan E -- Oskarsson, Hogni -- Tyrfingsson, Thorarinn -- Gudbjartsson, Daniel F -- Gulcher, Jeffrey R -- Jonsson, Steinn -- Thorsteinsdottir, Unnur -- Kong, Augustine -- Stefansson, Kari -- R01 DA017932/DA/NIDA NIH HHS/ -- England -- Nature. 2008 Apr 3;452(7187):638-42. doi: 10.1038/nature06846.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE Genetics, 101 Reykjavik, Iceland. thorgeir@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18385739" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Human, Pair 15/*genetics ; Europe ; Female ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Lung Neoplasms/*genetics ; Male ; Multigene Family/genetics ; New Zealand ; Odds Ratio ; Peripheral Vascular Diseases/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Receptors, Nicotinic/*genetics ; Smoking/adverse effects/genetics ; Tobacco Use Disorder/*genetics
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  • 78
    Publication Date: 2008-08-22
    Description: Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure-well into the tenth decade of life.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848880/" 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/PMC2848880/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Xiaocong -- Tsibane, Tshidi -- McGraw, Patricia A -- House, Frances S -- Keefer, Christopher J -- Hicar, Mark D -- Tumpey, Terrence M -- Pappas, Claudia -- Perrone, Lucy A -- Martinez, Osvaldo -- Stevens, James -- Wilson, Ian A -- Aguilar, Patricia V -- Altschuler, Eric L -- Basler, Christopher F -- Crowe, James E Jr -- AI057158/AI/NIAID NIH HHS/ -- AI42266/AI/NIAID NIH HHS/ -- CA55896/CA/NCI NIH HHS/ -- P01 AI058113/AI/NIAID NIH HHS/ -- R01 AI048677/AI/NIAID NIH HHS/ -- R01 AI048677-04/AI/NIAID NIH HHS/ -- U19 AI057229/AI/NIAID NIH HHS/ -- U19 AI62623/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54 AI057157-019002/AI/NIAID NIH HHS/ -- U54 AI57158/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Sep 25;455(7212):532-6. doi: 10.1038/nature07231. Epub 2008 Aug 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18716625" target="_blank"〉PubMed〈/a〉
    Keywords: Aged, 80 and over ; Animals ; Antibodies, Monoclonal/genetics/immunology/isolation & purification ; Antibodies, Viral/genetics/*immunology/*isolation & purification ; B-Lymphocytes/*immunology ; Cell Line ; Cross Reactions/immunology ; *Disease Outbreaks/history ; Dogs ; Female ; History, 20th Century ; Humans ; Influenza A Virus, H1N1 Subtype/genetics/*immunology/physiology ; Influenza, Human/*immunology/virology ; Kinetics ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Neutralization Tests ; *Survival
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  • 79
    Publication Date: 2008-01-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Threadgill, David W -- England -- Nature. 2008 Jan 3;451(7174):21-2. doi: 10.1038/451021a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172483" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Mammalian/genetics ; *Disease Models, Animal ; Down Syndrome/*complications/*genetics/pathology ; Female ; Gene Dosage ; Genes, APC/*physiology ; Humans ; Male ; Mice ; Neoplasms/complications/epidemiology/*genetics/*prevention & control ; Proto-Oncogene Protein c-ets-2/genetics/metabolism ; Trisomy/*genetics
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  • 80
    Publication Date: 2008-07-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kosik, Kenneth S -- Lopera, Francisco -- England -- Nature. 2008 Jul 10;454(7201):158-9. doi: 10.1038/454158c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18615057" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alzheimer Disease/epidemiology/genetics/psychology/therapy ; Colombia/epidemiology ; Female ; Genetic Counseling/psychology ; Genetic Predisposition to Disease/genetics ; Genetic Testing/*psychology ; Humans ; Male ; Middle Aged ; Patients/*psychology ; Suicide/psychology
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  • 81
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dennis, Carina -- England -- Nature. 2008 May 29;453(7195):575. doi: 10.1038/453575a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18509405" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; *Biological Evolution ; Female ; Fishes/*embryology/*physiology ; *Fossils ; History, Ancient ; Male ; Sharks/embryology/physiology ; *Viviparity, Nonmammalian
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  • 82
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2008-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2008 Mar 20;452(7185):254. doi: 10.1038/452254a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354433" target="_blank"〉PubMed〈/a〉
    Keywords: Amputation ; Drug Industry/*legislation & jurisprudence ; Drug Labeling/*legislation & jurisprudence/*standards ; Female ; Humans ; Promethazine/administration & dosage/adverse effects ; Risk Assessment ; *Supreme Court Decisions ; United States ; United States Food and Drug Administration/legislation & jurisprudence/standards
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  • 83
    Publication Date: 2008-12-05
    Description: Species-specific recognition between the egg extracellular matrix (zona pellucida) and sperm is the first, crucial step of mammalian fertilization. Zona pellucida filament components ZP3 and ZP2 act as sperm receptors, and mice lacking either of the corresponding genes produce oocytes without a zona pellucida and are completely infertile. Like their counterparts in the vitelline envelope of non-mammalian eggs and many other secreted eukaryotic proteins, zona pellucida subunits polymerize using a 'zona pellucida (ZP) domain' module, whose conserved amino-terminal part (ZP-N) was suggested to constitute a domain of its own. No atomic structure has been reported for ZP domain proteins, and there is no structural information on any conserved vertebrate protein that is essential for fertilization and directly involved in egg-sperm binding. Here we describe the 2.3 angstrom (A) resolution structure of the ZP-N fragment of mouse primary sperm receptor ZP3. The ZP-N fold defines a new immunoglobulin superfamily subtype with a beta-sheet extension characterized by an E' strand and an invariant tyrosine residue implicated in polymerization. The structure strongly supports the presence of ZP-N repeats within the N-terminal region of ZP2 and other vertebrate zona pellucida/vitelline envelope proteins, with implications for overall egg coat architecture, the post-fertilization block to polyspermy and speciation. Moreover, it provides an important framework for understanding human diseases caused by mutations in ZP domain proteins and developing new methods of non-hormonal contraception.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monne, Magnus -- Han, Ling -- Schwend, Thomas -- Burendahl, Sofia -- Jovine, Luca -- G0500367/Medical Research Council/United Kingdom -- England -- Nature. 2008 Dec 4;456(7222):653-7. doi: 10.1038/nature07599.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Karolinska Institutet, Department of Biosciences and Nutrition, Halsovagen 7, SE-141 57 Huddinge, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052627" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; CHO Cells ; Conserved Sequence ; Cricetinae ; Cricetulus ; Crystallization ; Crystallography, X-Ray ; Egg Proteins/*chemistry/genetics/*metabolism ; Female ; Male ; Membrane Glycoproteins/*chemistry/genetics/*metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Ovum/*chemistry/*metabolism ; Peptide Fragments/chemistry/genetics/metabolism ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Repetitive Sequences, Amino Acid ; Spermatozoa/metabolism
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  • 84
    Publication Date: 2008-06-13
    Description: Selective lowering of Abeta42 levels (the 42-residue isoform of the amyloid-beta peptide) with small-molecule gamma-secretase modulators (GSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. To identify the target of these agents we developed biotinylated photoactivatable GSMs. GSM photoprobes did not label the core proteins of the gamma-secretase complex, but instead labelled the beta-amyloid precursor protein (APP), APP carboxy-terminal fragments and amyloid-beta peptide in human neuroglioma H4 cells. Substrate labelling was competed by other GSMs, and labelling of an APP gamma-secretase substrate was more efficient than a Notch substrate. GSM interaction was localized to residues 28-36 of amyloid-beta, a region critical for aggregation. We also demonstrate that compounds known to interact with this region of amyloid-beta act as GSMs, and some GSMs alter the production of cell-derived amyloid-beta oligomers. Furthermore, mutation of the GSM binding site in the APP alters the sensitivity of the substrate to GSMs. These findings indicate that substrate targeting by GSMs mechanistically links two therapeutic actions: alteration in Abeta42 production and inhibition of amyloid-beta aggregation, which may synergistically reduce amyloid-beta deposition in Alzheimer's disease. These data also demonstrate the existence and feasibility of 'substrate targeting' by small-molecule effectors of proteolytic enzymes, which if generally applicable may significantly broaden the current notion of 'druggable' targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678541/" 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/PMC2678541/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kukar, Thomas L -- Ladd, Thomas B -- Bann, Maralyssa A -- Fraering, Patrick C -- Narlawar, Rajeshwar -- Maharvi, Ghulam M -- Healy, Brent -- Chapman, Robert -- Welzel, Alfred T -- Price, Robert W -- Moore, Brenda -- Rangachari, Vijayaraghavan -- Cusack, Bernadette -- Eriksen, Jason -- Jansen-West, Karen -- Verbeeck, Christophe -- Yager, Debra -- Eckman, Christopher -- Ye, Wenjuan -- Sagi, Sarah -- Cottrell, Barbara A -- Torpey, Justin -- Rosenberry, Terrone L -- Fauq, Abdul -- Wolfe, Michael S -- Schmidt, Boris -- Walsh, Dominic M -- Koo, Edward H -- Golde, Todd E -- P01 AG020206/AG/NIA NIH HHS/ -- P01 AG020206-010002/AG/NIA NIH HHS/ -- R01 AG017574/AG/NIA NIH HHS/ -- R01 AG017574-08/AG/NIA NIH HHS/ -- R01 AG017574-09/AG/NIA NIH HHS/ -- R01 NS041355/NS/NINDS NIH HHS/ -- R01 NS041355-06A2/NS/NINDS NIH HHS/ -- R01 NS041355-07/NS/NINDS NIH HHS/ -- England -- Nature. 2008 Jun 12;453(7197):925-9. doi: 10.1038/nature07055.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA. kukar.thomas@mayo.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18548070" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/drug therapy/enzymology/metabolism ; Amyloid Precursor Protein Secretases/*antagonists & inhibitors/*metabolism ; Amyloid beta-Protein Precursor/antagonists & ; inhibitors/*chemistry/genetics/*metabolism ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/*metabolism/*pharmacology ; Binding Sites/drug effects ; CHO Cells ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Female ; Humans ; Mice ; Protein Binding/drug effects ; Receptors, Notch/genetics/metabolism ; Substrate Specificity/drug effects
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  • 85
    Publication Date: 2008-08-30
    Description: Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672043/" 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/PMC2672043/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mosse, Yael P -- Laudenslager, Marci -- Longo, Luca -- Cole, Kristina A -- Wood, Andrew -- Attiyeh, Edward F -- Laquaglia, Michael J -- Sennett, Rachel -- Lynch, Jill E -- Perri, Patrizia -- Laureys, Genevieve -- Speleman, Frank -- Kim, Cecilia -- Hou, Cuiping -- Hakonarson, Hakon -- Torkamani, Ali -- Schork, Nicholas J -- Brodeur, Garrett M -- Tonini, Gian P -- Rappaport, Eric -- Devoto, Marcella -- Maris, John M -- K08 CA111733/CA/NCI NIH HHS/ -- K08 CA111733-04/CA/NCI NIH HHS/ -- K08-111733/PHS HHS/ -- R01 CA078545/CA/NCI NIH HHS/ -- R01 CA078545-09/CA/NCI NIH HHS/ -- R01 CA124709/CA/NCI NIH HHS/ -- R01-CA78454/CA/NCI NIH HHS/ -- R01-CA87847/CA/NCI NIH HHS/ -- U10 CA098543/CA/NCI NIH HHS/ -- U10 CA098543-06/CA/NCI NIH HHS/ -- England -- Nature. 2008 Oct 16;455(7215):930-5. doi: 10.1038/nature07261. Epub 2008 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18724359" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line, Tumor ; Child ; Chromosomes, Human, Pair 2/genetics ; Female ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/genetics ; Humans ; Male ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Neuroblastoma/*enzymology/*genetics ; Pedigree ; Phosphorylation ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry/deficiency/*genetics ; Receptor Protein-Tyrosine Kinases
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  • 86
    Publication Date: 2008-10-25
    Description: Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694412/" 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/PMC2694412/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Li -- Getz, Gad -- Wheeler, David A -- Mardis, Elaine R -- McLellan, Michael D -- Cibulskis, Kristian -- Sougnez, Carrie -- Greulich, Heidi -- Muzny, Donna M -- Morgan, Margaret B -- Fulton, Lucinda -- Fulton, Robert S -- Zhang, Qunyuan -- Wendl, Michael C -- Lawrence, Michael S -- Larson, David E -- Chen, Ken -- Dooling, David J -- Sabo, Aniko -- Hawes, Alicia C -- Shen, Hua -- Jhangiani, Shalini N -- Lewis, Lora R -- Hall, Otis -- Zhu, Yiming -- Mathew, Tittu -- Ren, Yanru -- Yao, Jiqiang -- Scherer, Steven E -- Clerc, Kerstin -- Metcalf, Ginger A -- Ng, Brian -- Milosavljevic, Aleksandar -- Gonzalez-Garay, Manuel L -- Osborne, John R -- Meyer, Rick -- Shi, Xiaoqi -- Tang, Yuzhu -- Koboldt, Daniel C -- Lin, Ling -- Abbott, Rachel -- Miner, Tracie L -- Pohl, Craig -- Fewell, Ginger -- Haipek, Carrie -- Schmidt, Heather -- Dunford-Shore, Brian H -- Kraja, Aldi -- Crosby, Seth D -- Sawyer, Christopher S -- Vickery, Tammi -- Sander, Sacha -- Robinson, Jody -- Winckler, Wendy -- Baldwin, Jennifer -- Chirieac, Lucian R -- Dutt, Amit -- Fennell, Tim -- Hanna, Megan -- Johnson, Bruce E -- Onofrio, Robert C -- Thomas, Roman K -- Tonon, Giovanni -- Weir, Barbara A -- Zhao, Xiaojun -- Ziaugra, Liuda -- Zody, Michael C -- Giordano, Thomas -- Orringer, Mark B -- Roth, Jack A -- Spitz, Margaret R -- Wistuba, Ignacio I -- Ozenberger, Bradley -- Good, Peter J -- Chang, Andrew C -- Beer, David G -- Watson, Mark A -- Ladanyi, Marc -- Broderick, Stephen -- Yoshizawa, Akihiko -- Travis, William D -- Pao, William -- Province, Michael A -- Weinstock, George M -- Varmus, Harold E -- Gabriel, Stacey B -- Lander, Eric S -- Gibbs, Richard A -- Meyerson, Matthew -- Wilson, Richard K -- P50 CA070907/CA/NCI NIH HHS/ -- R01 CA154365/CA/NCI NIH HHS/ -- U19 CA084953/CA/NCI NIH HHS/ -- U19 CA084953-050003/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-04/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- England -- Nature. 2008 Oct 23;455(7216):1069-75. doi: 10.1038/nature07423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center at Washington University, Department of Genetics, Washington University School of Medicine, St Louis, Missouri 63108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948947" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma, Bronchiolo-Alveolar/*genetics ; Female ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Lung Neoplasms/*genetics ; Male ; Mutation/*genetics ; Proto-Oncogenes/genetics
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  • 87
    Publication Date: 2008-10-17
    Description: Service providers may vary service quality depending on whether they work alone or provide the service simultaneously with a partner. The latter case resembles a prisoner's dilemma, in which one provider may try to reap the benefits of the interaction without providing the service. Here we present a game-theory model based on the marginal value theorem, which predicts that as long as the client determines the duration, and the providers cooperate towards mutual gain, service quality will increase in the pair situation. This prediction is consistent with field observations and with an experiment on cleaning mutualism, in which stable male-female pairs of the cleaner wrasse Labroides dimidiatus repeatedly inspect client fish jointly. Cleaners cooperate by eating ectoparasites off clients but actually prefer to cheat and eat client mucus. Because clients often leave in response to such cheating, the benefits of cheating can be gained by only one cleaner during a pair inspection. In both data sets, the increased service quality during pair inspection was mainly due to the smaller females behaving significantly more cooperatively than their larger male partners. In contrast, during solitary inspections, cleaning behaviour was very similar between the sexes. Our study highlights the importance of incorporating interactions between service providers to make more quantitative predictions about cooperation between species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bshary, Redouan -- Grutter, Alexandra S -- Willener, Astrid S T -- Leimar, Olof -- England -- Nature. 2008 Oct 16;455(7215):964-6. doi: 10.1038/nature07184.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Neuchatel, Department of Zoology, Rue Emile-Argand 11 Case postale 158, 2009 Neuchatel, Switzerland. redouan.bshary@unine.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18923522" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cooperative Behavior ; Feeding Behavior/*physiology ; Female ; Fishes/*physiology ; Game Theory ; Male ; Models, Biological ; Mucus ; *Parasites ; Sex Characteristics ; Swimming/physiology ; *Symbiosis
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  • 88
    Publication Date: 2008-09-23
    Description: The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB. However, their respective species specificity has complicated investigations on their in vivo role. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Disson, Olivier -- Grayo, Solene -- Huillet, Eugenie -- Nikitas, Georgios -- Langa-Vives, Francina -- Dussurget, Olivier -- Ragon, Marie -- Le Monnier, Alban -- Babinet, Charles -- Cossart, Pascale -- Lecuit, Marc -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 23;455(7216):1114-8. doi: 10.1038/nature07303. Epub 2008 Sep 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Pasteur, Groupe Microorganismes et Barrieres de l'Hote, Unite des Interactions Bacteries-Cellules, F-75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18806773" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/*metabolism ; Cadherins/genetics ; Cells, Cultured ; Disease Models, Animal ; Enterocytes/microbiology ; Epithelial Cells/microbiology ; Female ; Fetal Diseases/*microbiology ; Gerbillinae ; Humans ; Listeria monocytogenes/*physiology ; Listeriosis/microbiology/*transmission ; *Maternal-Fetal Exchange ; Membrane Proteins/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Placenta Diseases/*microbiology ; Pregnancy ; Pregnancy Complications, Infectious/metabolism/microbiology ; Protein Binding ; Receptors, Growth Factor/metabolism ; Species Specificity
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  • 89
    Publication Date: 2008-10-14
    Description: Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1beta and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1beta. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1beta and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saitoh, Tatsuya -- Fujita, Naonobu -- Jang, Myoung Ho -- Uematsu, Satoshi -- Yang, Bo-Gie -- Satoh, Takashi -- Omori, Hiroko -- Noda, Takeshi -- Yamamoto, Naoki -- Komatsu, Masaaki -- Tanaka, Keiji -- Kawai, Taro -- Tsujimura, Tohru -- Takeuchi, Osamu -- Yoshimori, Tamotsu -- Akira, Shizuo -- AI070167/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Nov 13;456(7219):264-8. doi: 10.1038/nature07383. Epub 2008 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18849965" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/analogs & derivatives/pharmacology ; Animals ; Autophagy/*genetics ; Carrier Proteins/*genetics ; Chimera ; Colitis/chemically induced/immunology ; Dextran Sulfate/pharmacology ; Female ; Gene Expression Regulation/*drug effects ; Interleukin-1beta/*biosynthesis/metabolism ; Lipopolysaccharides/*pharmacology ; Macrophages/*drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Mutation
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  • 90
    Publication Date: 2008-02-12
    Description: Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577037/" 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/PMC2577037/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakai, Wataru -- Swisher, Elizabeth M -- Karlan, Beth Y -- Agarwal, Mukesh K -- Higgins, Jake -- Friedman, Cynthia -- Villegas, Emily -- Jacquemont, Celine -- Farrugia, Daniel J -- Couch, Fergus J -- Urban, Nicole -- Taniguchi, Toshiyasu -- K08 CA096610/CA/NCI NIH HHS/ -- K08 CA096610-01/CA/NCI NIH HHS/ -- P50 CA083636/CA/NCI NIH HHS/ -- P50 CA083636-10/CA/NCI NIH HHS/ -- R01 CA125636/CA/NCI NIH HHS/ -- R01 CA125636-02/CA/NCI NIH HHS/ -- England -- Nature. 2008 Feb 28;451(7182):1116-20. doi: 10.1038/nature06633. Epub 2008 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18264087" target="_blank"〉PubMed〈/a〉
    Keywords: Azulenes/pharmacology ; BRCA2 Protein/genetics/metabolism ; Benzodiazepines/pharmacology ; Breast Neoplasms/drug therapy/genetics/pathology ; Cell Line, Tumor ; Cisplatin/*pharmacology ; Drug Resistance, Neoplasm/*drug effects/*genetics ; Female ; *Genes, BRCA2 ; Humans ; Middle Aged ; Mutation/*genetics ; Neoplasms/*drug therapy/*genetics ; Ovarian Neoplasms/drug therapy/genetics ; Pancreatic Neoplasms/drug therapy/genetics/pathology ; Poly(ADP-ribose) Polymerase Inhibitors
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  • 91
    Publication Date: 2008-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Grace Y -- Brumell, John H -- England -- Nature. 2008 Oct 30;455(7217):1186-7. doi: 10.1038/4551186a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18972010" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Animals ; Bacterial Toxins/metabolism ; Female ; Heat-Shock Proteins/metabolism ; Hemolysin Proteins/metabolism ; Humans ; Infant, Newborn ; Listeria monocytogenes/growth & development/pathogenicity/*physiology ; Listeriosis/*metabolism/*microbiology ; Macrophages/cytology/metabolism/microbiology ; Mice ; Oxidoreductases/genetics/*metabolism ; Phagosomes/microbiology ; Pregnancy ; Virulence Factors/metabolism
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  • 92
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomasello, Michael -- Warneken, Felix -- England -- Nature. 2008 Aug 28;454(7208):1057-8. doi: 10.1038/4541057a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18756241" target="_blank"〉PubMed〈/a〉
    Keywords: *Altruism ; Animals ; Candy ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Pan troglodytes/physiology ; Reward ; Social Justice
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  • 93
    Publication Date: 2008-03-21
    Description: A key aspect of human behaviour is cooperation. We tend to help others even if costs are involved. We are more likely to help when the costs are small and the benefits for the other person significant. Cooperation leads to a tension between what is best for the individual and what is best for the group. A group does better if everyone cooperates, but each individual is tempted to defect. Recently there has been much interest in exploring the effect of costly punishment on human cooperation. Costly punishment means paying a cost for another individual to incur a cost. It has been suggested that costly punishment promotes cooperation even in non-repeated games and without any possibility of reputation effects. But most of our interactions are repeated and reputation is always at stake. Thus, if costly punishment is important in promoting cooperation, it must do so in a repeated setting. We have performed experiments in which, in each round of a repeated game, people choose between cooperation, defection and costly punishment. In control experiments, people could only cooperate or defect. Here we show that the option of costly punishment increases the amount of cooperation but not the average payoff of the group. Furthermore, there is a strong negative correlation between total payoff and use of costly punishment. Those people who gain the highest total payoff tend not to use costly punishment: winners don't punish. This suggests that costly punishment behaviour is maladaptive in cooperation games and might have evolved for other reasons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292414/" 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/PMC2292414/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dreber, Anna -- Rand, David G -- Fudenberg, Drew -- Nowak, Martin A -- R01 GM078986/GM/NIGMS NIH HHS/ -- R01 GM078986-02/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Mar 20;452(7185):348-51. doi: 10.1038/nature06723.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354481" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Altruism ; Biological Evolution ; *Cooperative Behavior ; Female ; *Game Theory ; Humans ; Male ; Models, Psychological ; Punishment/*psychology ; Risk Assessment
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  • 94
    Publication Date: 2008-03-21
    Description: Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakao, Nobuhiro -- Ono, Hiroko -- Yamamura, Takashi -- Anraku, Tsubasa -- Takagi, Tsuyoshi -- Higashi, Kumiko -- Yasuo, Shinobu -- Katou, Yasuhiro -- Kageyama, Saburo -- Uno, Yumiko -- Kasukawa, Takeya -- Iigo, Masayuki -- Sharp, Peter J -- Iwasawa, Atsushi -- Suzuki, Yutaka -- Sugano, Sumio -- Niimi, Teruyuki -- Mizutani, Makoto -- Namikawa, Takao -- Ebihara, Shizufumi -- Ueda, Hiroki R -- Yoshimura, Takashi -- England -- Nature. 2008 Mar 20;452(7185):317-22. doi: 10.1038/nature06738.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biomodelling, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354476" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chickens ; Coturnix/anatomy & histology/genetics/*physiology ; Cyclic AMP/metabolism ; Darkness ; Enzyme Induction ; Female ; Gene Expression Regulation/radiation effects ; Genome ; Genomics ; Hypothalamus/metabolism/radiation effects ; Iodide Peroxidase/biosynthesis/genetics/metabolism ; Light ; Luteinizing Hormone/secretion ; Male ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; *Photoperiod ; Pituitary Gland/anatomy & histology/*metabolism/*radiation effects ; Receptors, Thyrotropin/metabolism ; Reproduction/*physiology/*radiation effects ; Seasons ; Signal Transduction/radiation effects ; Testis/growth & development ; Thyrotropin/administration & dosage/antagonists & ; inhibitors/immunology/*metabolism
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  • 95
    Publication Date: 2008-03-21
    Description: In the classical model of chick wing digit-patterning, the polarizing region--a group of cells at the posterior margin of the early bud--produces a morphogen gradient, now known to be based on Sonic hedgehog (Shh), that progressively specifies anteroposterior positional identities in the posterior digit-forming region. Here we add an integral growth component to this model by showing that Shh-dependent proliferation of prospective digit progenitor cells is essential for specifying the complete pattern of digits across the anteroposterior axis. Inhibiting Shh signalling in early wing buds reduced anteroposterior expansion, and posterior digits were lost because all prospective digit precursors formed anterior structures. Inhibiting proliferation also irreversibly reduced anteroposterior expansion, but instead anterior digits were lost because all prospective digit precursors formed posterior structures. When proliferation recovered in such wings, Shh transcription was maintained for longer than normal, suggesting that duration of Shh expression is controlled by a mechanism that measures proliferation. Rescue experiments confirmed that Shh-dependent proliferation controls digit number during a discrete time-window in which Shh-dependent specification normally occurs. Our findings that Shh signalling has dual functions that can be temporally uncoupled have implications for understanding congenital and evolutionary digit reductions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Towers, Matthew -- Mahood, Ruth -- Yin, Yili -- Tickle, Cheryll -- G9806660/Medical Research Council/United Kingdom -- England -- Nature. 2008 Apr 17;452(7189):882-6. doi: 10.1038/nature06718. Epub 2008 Mar 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cell and Developmental Biology, WTB/MSI Complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18354396" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; Chick Embryo ; Female ; Hedgehog Proteins/metabolism ; Limb Buds/cytology/embryology ; Models, Biological ; Wings, Animal/*anatomy & histology/cytology/*embryology
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  • 96
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    Nature Publishing Group (NPG)
    Publication Date: 2008-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nath, Indira -- England -- Nature. 2008 Jun 19;453(7198):1002. doi: 10.1038/4531002a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Indira Nath is in the LEPRA - Blue Peter Research Centre, Cherlapally, Hyderabad 501301, India. indiranath@bprcleprasociety.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18563148" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child ; Culicidae/genetics/*physiology ; Developing Countries ; Female ; Great Britain ; History, 20th Century ; History, 21st Century ; Humans ; Insect Control/*history ; Malaria/*prevention & control/transmission ; Pregnancy ; Public Health/history
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  • 97
    Publication Date: 2008-08-15
    Description: Recognition of self-antigen-derived epitopes presented by major histocompatibility complex class II (MHC II) molecules on thymic epithelial cells (TECs) is critical for the generation of a functional and self-tolerant CD4 T-cell repertoire. Whereas haematopoietic antigen-presenting cells generate MHC-II-peptide complexes predominantly through the processing of endocytosed polypeptides, it remains unknown if and how TECs use unconventional pathways of antigen presentation. Here we address the role of macroautophagy, a process that has recently been shown to allow for endogenous MHC II loading, in T-cell repertoire selection in the mouse thymus. In contrast to most other tissues, TECs had a high constitutive level of autophagy. Genetic interference with autophagy specifically in TECs led to altered selection of certain MHC-II-restricted T-cell specificities and resulted in severe colitis and multi-organ inflammation. Our findings indicate that autophagy focuses the MHC-II-peptide repertoire of TECs on their intracellular milieu, which notably comprises a wide array of otherwise strictly 'tissue-specific' self antigens. In doing so, it contributes to T-cell selection and is essential for the generation of a self-tolerant T-cell repertoire.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nedjic, Jelena -- Aichinger, Martin -- Emmerich, Jan -- Mizushima, Noboru -- Klein, Ludger -- England -- Nature. 2008 Sep 18;455(7211):396-400. doi: 10.1038/nature07208. Epub 2008 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Doktor Bohr Gasse 7, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18701890" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Cell Differentiation ; Chimera/immunology ; Colitis/genetics/immunology/metabolism ; Epithelial Cells/cytology/immunology ; Epithelium/*immunology ; Female ; Histocompatibility Antigens/immunology ; Immune Tolerance/*immunology ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/deficiency/genetics ; Receptors, Antigen, T-Cell/immunology ; Stromal Cells/cytology ; T-Lymphocytes/*cytology/*immunology ; Thymus Gland/*cytology/*immunology/transplantation
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  • 98
    Publication Date: 2008-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eaton, Charles -- England -- Nature. 2008 Jan 31;451(7178):520-1. doi: 10.1038/451520c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18235475" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Attention/*drug effects/physiology ; Benzhydryl Compounds/administration & dosage/*pharmacology/therapeutic use ; Child ; Competitive Behavior/drug effects ; Family Health ; Fatigue/*drug therapy ; Female ; Humans ; Male
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  • 99
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    Nature Publishing Group (NPG)
    Publication Date: 2008-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trivedi, Bijal -- England -- Nature. 2008 Apr 24;452(7190):926-9. doi: 10.1038/452926a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18441548" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Biomedical Research/economics/*trends ; Child ; Databases, Factual/economics/*trends ; Diagnostic Tests, Routine ; Diet/statistics & numerical data ; Environment ; *Family Health ; Female ; Genealogy and Heraldry ; Genetic Predisposition to Disease ; *Health Surveys ; Humans ; Internationality ; Male ; Medical Records ; Polymorphism, Single Nucleotide ; Western Australia/epidemiology
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  • 100
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    Nature Publishing Group (NPG)
    Publication Date: 2008-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2008 Dec 4;456(7222):556. doi: 10.1038/456556a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19052591" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/diagnosis/genetics ; Europe ; Female ; *Genes, BRCA1 ; Genetic Testing/*economics ; Humans ; Neoplasms/*diagnosis/*genetics ; Ovarian Neoplasms/diagnosis/genetics ; Patents as Topic/*legislation & jurisprudence ; Utah
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