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  • Female  (272)
  • Models, Biological  (119)
  • Nature Publishing Group (NPG)  (374)
  • 2005-2009  (374)
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  • 1
    Publication Date: 2009-12-23
    Description: Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (〈0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons (fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly (1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase (AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide new evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutani, Nidhi -- Brady, Jennifer J -- Damian, Mara -- Sacco, Alessandra -- Corbel, Stephane Y -- Blau, Helen M -- AG009521/AG/NIA NIH HHS/ -- AG024987/AG/NIA NIH HHS/ -- AI007328/AI/NIAID NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG024987/AG/NIA NIH HHS/ -- R01 AG024987-05/AG/NIA NIH HHS/ -- T32 AI007328/AI/NIAID NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1042-7. doi: 10.1038/nature08752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20027182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Fusion ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; Chromatin Immunoprecipitation ; Cytidine Deaminase/deficiency/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; DNA Replication ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/*cytology/enzymology/*metabolism ; Lung/cytology/embryology ; Mice ; Models, Biological ; Octamer Transcription Factor-3/genetics ; Promoter Regions, Genetic/genetics ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    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
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2009 Jan 22;457(7228):369. doi: 10.1038/457369a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158758" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breeding/economics/*methods ; Cattle/*genetics ; Dairying/economics/*methods ; Female ; Internationality ; Male ; Milk/*secretion/*standards ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; United States ; United States Department of Agriculture
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2009-08-12
    Description: Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes, but the low frequency and tendency to induce malignant transformation compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 (also known as Pou5f1) and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735889/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735889/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawamura, Teruhisa -- Suzuki, Jotaro -- Wang, Yunyuan V -- Menendez, Sergio -- Morera, Laura Batlle -- Raya, Angel -- Wahl, Geoffrey M -- Izpisua Belmonte, Juan Carlos -- 5 R01 CA061449/CA/NCI NIH HHS/ -- 5 R01 CA100845/CA/NCI NIH HHS/ -- R01 CA061449/CA/NCI NIH HHS/ -- R01 CA061449-30/CA/NCI NIH HHS/ -- R01 CA100845/CA/NCI NIH HHS/ -- R01 CA100845-05/CA/NCI NIH HHS/ -- R33 HL088293/HL/NHLBI NIH HHS/ -- R33 HL088293-03/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1140-4. doi: 10.1038/nature08311. Epub 2009 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19668186" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cellular Reprogramming/*physiology ; Cyclin-Dependent Kinase Inhibitor p21/deficiency/genetics/metabolism ; Down-Regulation ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Keratinocytes ; Male ; Mice ; Mice, Inbred C57BL ; Pluripotent Stem Cells/*cytology/*metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
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  • 5
    Publication Date: 2009-09-26
    Description: India has been underrepresented in genome-wide surveys of human variation. We analyse 25 diverse groups in India to provide strong evidence for two ancient populations, genetically divergent, that are ancestral to most Indians today. One, the 'Ancestral North Indians' (ANI), is genetically close to Middle Easterners, Central Asians, and Europeans, whereas the other, the 'Ancestral South Indians' (ASI), is as distinct from ANI and East Asians as they are from each other. By introducing methods that can estimate ancestry without accurate ancestral populations, we show that ANI ancestry ranges from 39-71% in most Indian groups, and is higher in traditionally upper caste and Indo-European speakers. Groups with only ASI ancestry may no longer exist in mainland India. However, the indigenous Andaman Islanders are unique in being ASI-related groups without ANI ancestry. Allele frequency differences between groups in India are larger than in Europe, reflecting strong founder effects whose signatures have been maintained for thousands of years owing to endogamy. We therefore predict that there will be an excess of recessive diseases in India, which should be possible to screen and map genetically.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842210/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842210/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reich, David -- Thangaraj, Kumarasamy -- Patterson, Nick -- Price, Alkes L -- Singh, Lalji -- HG004168/HG/NHGRI NIH HHS/ -- R01 HG006399/HG/NHGRI NIH HHS/ -- U01 HG004168/HG/NHGRI NIH HHS/ -- U01 HG004168-03/HG/NHGRI NIH HHS/ -- England -- Nature. 2009 Sep 24;461(7263):489-94. doi: 10.1038/nature08365.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. reich@genetics.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779445" target="_blank"〉PubMed〈/a〉
    Keywords: Asia/ethnology ; Chromosomes, Human, Y/genetics ; Continental Population Groups/genetics ; DNA, Mitochondrial/genetics ; Ethnic Groups/*genetics ; Europe/ethnology ; Female ; Founder Effect ; Gene Frequency ; Genes, Recessive/genetics ; Genetic Variation/*genetics ; Genetics, Medical ; Genetics, Population ; Genome, Human/genetics ; Genomics ; Genotype ; Geography ; Humans ; India ; Language ; Linkage Disequilibrium/genetics ; Male ; Middle East/ethnology ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis
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  • 6
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    Nature Publishing Group (NPG)
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reiff, Sarah B -- Striepen, Boris -- England -- Nature. 2009 Jun 18;459(7249):918-9. doi: 10.1038/459918a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536248" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Malaria, Falciparum/drug therapy/*parasitology ; Models, Biological ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/antagonists & inhibitors/*metabolism ; Vacuoles/metabolism/parasitology
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Apr 2;458(7238):550. doi: 10.1038/458550a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19340028" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Enteral Nutrition/ethics/utilization ; Female ; Humans ; Italy ; Living Wills/ethics/*legislation & jurisprudence ; *Patients ; *Physicians ; Right to Die/ethics/*legislation & jurisprudence ; Young Adult
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  • 8
    Publication Date: 2009-10-30
    Description: The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133736/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kee, Kehkooi -- Angeles, Vanessa T -- Flores, Martha -- Nguyen, Ha Nam -- Reijo Pera, Renee A -- R01 HD047721/HD/NICHD NIH HHS/ -- R01 HD047721-06/HD/NICHD NIH HHS/ -- R01HD047721/HD/NICHD NIH HHS/ -- U54 HD055764/HD/NICHD NIH HHS/ -- U54 HD055764-015755/HD/NICHD NIH HHS/ -- U54HD055764/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):222-5. doi: 10.1038/nature08562. Epub 2009 Oct 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology & Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Palo Alto, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865085" target="_blank"〉PubMed〈/a〉
    Keywords: Bone Morphogenetic Proteins/metabolism ; Cell Count ; *Cell Differentiation ; Cell Line ; Cellular Reprogramming ; Embryonic Stem Cells/cytology/metabolism ; Female ; Gene Expression ; Gene Silencing ; Genes, Reporter ; Germ Cells/*cytology/*metabolism ; *Haploidy ; Humans ; Male ; Meiosis ; Organ Specificity ; RNA-Binding Proteins/genetics/*metabolism
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  • 9
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonnell, Anna -- England -- Nature. 2009 Jun 18;459(7249):909. doi: 10.1038/459909b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536241" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fertility ; History, Ancient ; Humans ; Pregnancy ; Sculpture/*history
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  • 10
    Publication Date: 2009-07-25
    Description: African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872475/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keele, Brandon F -- Jones, James Holland -- Terio, Karen A -- Estes, Jacob D -- Rudicell, Rebecca S -- Wilson, Michael L -- Li, Yingying -- Learn, Gerald H -- Beasley, T Mark -- Schumacher-Stankey, Joann -- Wroblewski, Emily -- Mosser, Anna -- Raphael, Jane -- Kamenya, Shadrack -- Lonsdorf, Elizabeth V -- Travis, Dominic A -- Mlengeya, Titus -- Kinsel, Michael J -- Else, James G -- Silvestri, Guido -- Goodall, Jane -- Sharp, Paul M -- Shaw, George M -- Pusey, Anne E -- Hahn, Beatrice H -- HHSN266200400088C/PHS HHS/ -- P30 AI 27767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A17134/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 AI58715/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-06A1/AI/NIAID NIH HHS/ -- RR-00165/RR/NCRR NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-059010/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 23;460(7254):515-9. doi: 10.1038/nature08200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626114" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/pathology ; Africa ; Animals ; Animals, Wild ; CD4-Positive T-Lymphocytes/immunology ; Female ; Humans ; Male ; Molecular Sequence Data ; Pan troglodytes/*virology ; Prevalence ; Simian Acquired Immunodeficiency ; Syndrome/epidemiology/immunology/*mortality/*pathology ; Simian Immunodeficiency Virus/*physiology
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  • 11
    Publication Date: 2009-08-21
    Description: A decision is a commitment to a proposition or plan of action based on evidence and the expected costs and benefits associated with the outcome. Progress in a variety of fields has led to a quantitative understanding of the mechanisms that evaluate evidence and reach a decision. Several formalisms propose that a representation of noisy evidence is evaluated against a criterion to produce a decision. Without additional evidence, however, these formalisms fail to explain why a decision-maker would change their mind. Here we extend a model, developed to account for both the timing and the accuracy of the initial decision, to explain subsequent changes of mind. Subjects made decisions about a noisy visual stimulus, which they indicated by moving a handle. Although they received no additional information after initiating their movement, their hand trajectories betrayed a change of mind in some trials. We propose that noisy evidence is accumulated over time until it reaches a criterion level, or bound, which determines the initial decision, and that the brain exploits information that is in the processing pipeline when the initial decision is made to subsequently either reverse or reaffirm the initial decision. The model explains both the frequency of changes of mind as well as their dependence on both task difficulty and whether the initial decision was accurate or erroneous. The theoretical and experimental findings advance the understanding of decision-making to the highly flexible and cognitive acts of vacillation and self-correction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875179/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875179/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Resulaj, Arbora -- Kiani, Roozbeh -- Wolpert, Daniel M -- Shadlen, Michael N -- 077730/Wellcome Trust/United Kingdom -- EY11378/EY/NEI NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Sep 10;461(7261):263-6. doi: 10.1038/nature08275. Epub 2009 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational and Biological Learning Laboratory, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693010" target="_blank"〉PubMed〈/a〉
    Keywords: Computers ; Cues ; Decision Making/*physiology ; Female ; Hand/physiology ; Humans ; Male ; Models, Neurological ; Models, Psychological ; Motion ; Movement ; Photic Stimulation ; Psychomotor Performance ; Reaction Time ; Time Factors
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  • 12
    Publication Date: 2009-08-28
    Description: Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774772/" 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/PMC2774772/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana, Masahito -- Sparman, Michelle -- Sritanaudomchai, Hathaitip -- Ma, Hong -- Clepper, Lisa -- Woodward, Joy -- Li, Ying -- Ramsey, Cathy -- Kolotushkina, Olena -- Mitalipov, Shoukhrat -- P01 HD047675/HD/NICHD NIH HHS/ -- P01 HD047675-01A17045/HD/NICHD NIH HHS/ -- P01 HD047675-04/HD/NICHD NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- P51 RR000163-486766/RR/NCRR NIH HHS/ -- P51 RR000163-486775/RR/NCRR NIH HHS/ -- P51 RR000163-486819/RR/NCRR NIH HHS/ -- P51 RR000163-496038/RR/NCRR NIH HHS/ -- P51 RR000163-496045/RR/NCRR NIH HHS/ -- P51 RR000163-496074/RR/NCRR NIH HHS/ -- P51 RR000163-496133/RR/NCRR NIH HHS/ -- P51 RR000163-496134/RR/NCRR NIH HHS/ -- P51 RR000163-496136/RR/NCRR NIH HHS/ -- P51 RR000163-496137/RR/NCRR NIH HHS/ -- R01 HD057121/HD/NICHD NIH HHS/ -- R01 HD057121-01A2/HD/NICHD NIH HHS/ -- R01 NS044330/NS/NINDS NIH HHS/ -- R01 NS044330-05/NS/NINDS NIH HHS/ -- R24 RR013632/RR/NCRR NIH HHS/ -- R24 RR013632-10/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):367-72. doi: 10.1038/nature08368. Epub 2009 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oregon National Primate Research Center, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19710649" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/analysis/*genetics ; Embryo Transfer ; Embryonic Stem Cells/*cytology/*metabolism/transplantation ; Female ; Fertilization in Vitro ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Macaca mulatta/embryology/*genetics ; Male ; Meiosis ; Mitochondrial Diseases/genetics/prevention & control ; Mutation ; Oocytes/cytology/metabolism ; Pregnancy ; *Reproductive Techniques, Assisted
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  • 13
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowans, James -- England -- Nature. 2009 May 28;459(7246):506. doi: 10.1038/459506c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478763" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials as Topic/history ; Correspondence as Topic/history ; Female ; Great Britain ; History, 20th Century ; Humans ; Periodicals as Topic/*history
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  • 14
    Publication Date: 2009-08-21
    Description: Activity is thought to guide the patterning of synaptic connections in the developing nervous system. Specifically, differences in the activity of converging inputs are thought to cause the elimination of synapses from less active inputs and increase connectivity with more active inputs. Here we present findings that challenge the generality of this notion and offer a new view of the role of activity in synapse development. To imbalance neurotransmission from different sets of inputs in vivo, we generated transgenic mice in which ON but not OFF types of bipolar cells in the retina express tetanus toxin (TeNT). During development, retinal ganglion cells (RGCs) select between ON and OFF bipolar cell inputs (ON or OFF RGCs) or establish a similar number of synapses with both on separate dendritic arborizations (ON-OFF RGCs). In TeNT retinas, ON RGCs correctly selected the silenced ON bipolar cell inputs over the transmitting OFF bipolar cells, but were connected with them through fewer synapses at maturity. Time-lapse imaging revealed that this was caused by a reduced rate of synapse formation rather than an increase in synapse elimination. Similarly, TeNT-expressing ON bipolar cell axons generated fewer presynaptic active zones. The remaining active zones often recruited multiple, instead of single, synaptic ribbons. ON-OFF RGCs in TeNT mice maintained convergence of ON and OFF bipolar cells inputs and had fewer synapses on their ON arbor without changes to OFF arbor synapses. Our results reveal an unexpected and remarkably selective role for activity in circuit development in vivo, regulating synapse formation but not elimination, affecting synapse number but not dendritic or axonal patterning, and mediating independently the refinement of connections from parallel (ON and OFF) processing streams even where they converge onto the same postsynaptic cell.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746695/" 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/PMC2746695/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kerschensteiner, Daniel -- Morgan, Josh L -- Parker, Edward D -- Lewis, Renate M -- Wong, Rachel O L -- EY01730/EY/NEI NIH HHS/ -- EY10699/EY/NEI NIH HHS/ -- R01 EY010699/EY/NEI NIH HHS/ -- R01 EY010699-16/EY/NEI NIH HHS/ -- T32 EY07031/EY/NEI NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1016-20. doi: 10.1038/nature08236.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA. KerschensteinerD@vision.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693082" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/metabolism ; Dendrites/metabolism ; Female ; Glutamic Acid/metabolism ; Male ; Mice ; Mice, Transgenic ; Receptors, Kainic Acid/genetics/metabolism ; Retinal Bipolar Cells/cytology/metabolism ; Retinal Ganglion Cells/cytology/metabolism ; Synapses/*metabolism ; Synaptic Transmission/*physiology ; Tetanus Toxin/genetics/metabolism
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  • 15
    Publication Date: 2009-12-04
    Description: Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms, and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798000/" 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/PMC2798000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grandison, Richard C -- Piper, Matthew D W -- Partridge, Linda -- 081394/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Dec 24;462(7276):1061-4. doi: 10.1038/nature08619. Epub 2009 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956092" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*metabolism ; Animals ; *Diet ; Drosophila melanogaster/metabolism/*physiology ; Female ; Insulin/metabolism ; Longevity/*physiology ; Methionine/metabolism ; Oviposition/physiology ; Random Allocation ; Signal Transduction
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  • 16
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    Nature Publishing Group (NPG)
    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellars, Paul -- England -- Nature. 2009 May 14;459(7244):176-7. doi: 10.1038/459176a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444200" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Archaeology ; Female ; Germany ; History, Ancient ; Horns/chemistry ; Humans ; Sculpture/*history ; Sex Characteristics ; Symbolism
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  • 17
    Publication Date: 2009-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khalil, Ahmad M -- England -- Nature. 2009 Mar 19;458(7236):263. doi: 10.1038/458263f.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Medical School, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; *Models, Genetic ; RNA Interference ; RNA, Long Noncoding ; RNA, Untranslated/*genetics ; Ribonuclease III/deficiency ; X Chromosome Inactivation/*genetics
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  • 18
    Publication Date: 2009-12-18
    Description: An important challenge in systems biology is to quantitatively describe microbial growth using a few measurable parameters that capture the essence of this complex phenomenon. Two key events at the cell membrane-extracellular glucose sensing and uptake-initiate the budding yeast's growth on glucose. However, conventional growth models focus almost exclusively on glucose uptake. Here we present results from growth-rate experiments that cannot be explained by focusing on glucose uptake alone. By imposing a glucose uptake rate independent of the sensed extracellular glucose level, we show that despite increasing both the sensed glucose concentration and uptake rate, the cell's growth rate can decrease or even approach zero. We resolve this puzzle by showing that the interaction between glucose perception and import, not their individual actions, determines the central features of growth, and characterize this interaction using a quantitative model. Disrupting this interaction by knocking out two key glucose sensors significantly changes the cell's growth rate, yet uptake rates are unchanged. This is due to a decrease in burden that glucose perception places on the cells. Our work shows that glucose perception and import are separate and pivotal modules of yeast growth, the interaction of which can be precisely tuned and measured.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796206/" 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/PMC2796206/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Youk, Hyun -- van Oudenaarden, Alexander -- DP1 OD003936/OD/NIH HHS/ -- DP1 OD003936-01/OD/NIH HHS/ -- DP1 OD003936-02/OD/NIH HHS/ -- R01 GM068957/GM/NIGMS NIH HHS/ -- R01 GM068957-06/GM/NIGMS NIH HHS/ -- R01 GM068957-07/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):875-9. doi: 10.1038/nature08653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016593" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport/drug effects ; Cell Growth Processes/drug effects ; Cell Membrane/drug effects/metabolism ; Doxycycline/pharmacology ; Glucose/*metabolism/pharmacology ; Kinetics ; Models, Biological ; Saccharomyces cerevisiae/cytology/drug effects/*growth & development/*metabolism
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  • 19
    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graves, Jennifer A Marshall -- England -- Nature. 2009 Sep 10;461(7261):177-8. doi: 10.1038/461177a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chick Embryo ; Chickens/*genetics/*physiology ; Disorders of Sex Development ; Evolution, Molecular ; Female ; Gene Dosage/genetics ; Humans ; Male ; Models, Genetic ; Ovary/embryology/metabolism ; RNA Interference ; SOX9 Transcription Factor/genetics/metabolism ; Sex Chromosomes/*genetics ; *Sex Determination Processes ; Testis/embryology/metabolism ; Transcription Factors/deficiency/*genetics/*metabolism
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  • 20
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Larry J -- England -- Nature. 2009 Jan 8;457(7226):148. doi: 10.1038/457148a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA. lyoun03@emory.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19129828" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/genetics/physiology ; Dopamine/metabolism ; Female ; Humans ; *Love ; Male ; Maternal Behavior/physiology ; Oxytocin/*metabolism ; Pair Bond ; Paternal Behavior ; Receptors, Vasopressin/genetics/metabolism ; Sexual Behavior/drug effects/physiology ; Vasopressins/*metabolism
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  • 21
    Publication Date: 2009-09-11
    Description: It is widely accepted that tissue differentiation and morphogenesis in multicellular organisms are regulated by tightly controlled concentration gradients of morphogens. How exactly these gradients are formed, however, remains unclear. Here we show that Fgf8 morphogen gradients in living zebrafish embryos are established and maintained by two essential factors: fast, free diffusion of single molecules away from the source through extracellular space, and a sink function of the receiving cells, regulated by receptor-mediated endocytosis. Evidence is provided by directly examining single molecules of Fgf8 in living tissue by fluorescence correlation spectroscopy, quantifying their local mobility and concentration with high precision. By changing the degree of uptake of Fgf8 into its target cells, we are able to alter the shape of the Fgf8 gradient. Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Shuizi Rachel -- Burkhardt, Markus -- Nowak, Matthias -- Ries, Jonas -- Petrasek, Zdenek -- Scholpp, Steffen -- Schwille, Petra -- Brand, Michael -- England -- Nature. 2009 Sep 24;461(7263):533-6. doi: 10.1038/nature08391. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Genetics, Biotechnology Center, TUD, Tatzberg 47-49, 01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741606" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diffusion ; Embryo, Nonmammalian/*cytology/embryology/*metabolism ; *Endocytosis ; Extracellular Space/metabolism ; Fibroblast Growth Factors/genetics/*metabolism ; Gastrulation ; Green Fluorescent Proteins/genetics/metabolism ; Models, Biological ; Morphogenesis/*physiology ; Receptors, Fibroblast Growth Factor/metabolism ; Zebrafish/*embryology/*metabolism ; Zebrafish Proteins/genetics/*metabolism
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  • 22
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    Nature Publishing Group (NPG)
    Publication Date: 2009-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2009 Dec 3;462(7273):562-4. doi: 10.1038/462562a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956235" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior/physiology ; *Behavior, Animal ; Behavioral Research/*instrumentation/methods ; Drosophila melanogaster/*physiology ; Female ; Humans ; Male ; Software ; Video Recording/instrumentation/methods
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  • 23
    Publication Date: 2009-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rockenbach, Bettina -- Milinski, Manfred -- England -- Nature. 2009 Jan 1;457(7225):39-40. doi: 10.1038/457039a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122632" target="_blank"〉PubMed〈/a〉
    Keywords: Altruism ; Biological Evolution ; *Cooperative Behavior ; Cost-Benefit Analysis ; Female ; *Game Theory ; Humans ; Male ; Models, Psychological ; *Punishment/psychology
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  • 24
    Publication Date: 2009-06-19
    Description: Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725363/" 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/PMC2725363/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Koning-Ward, Tania F -- Gilson, Paul R -- Boddey, Justin A -- Rug, Melanie -- Smith, Brian J -- Papenfuss, Anthony T -- Sanders, Paul R -- Lundie, Rachel J -- Maier, Alexander G -- Cowman, Alan F -- Crabb, Brendan S -- R01 AI044008-11/AI/NIAID NIH HHS/ -- R01 AI44008/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 18;459(7249):945-9. doi: 10.1038/nature08104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter & Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Malaria, Falciparum/*parasitology ; Models, Biological ; Multiprotein Complexes/*chemistry/*metabolism ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/*metabolism
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  • 25
    Publication Date: 2009-07-17
    Description: In recent years, strikingly consistent patterns of biodiversity have been identified over space, time, organism type and geographical region. A neutral theory (assuming no environmental selection or organismal interactions) has been shown to predict many patterns of ecological biodiversity. This theory is based on a mechanism by which new species arise similarly to point mutations in a population without sexual reproduction. Here we report the simulation of populations with sexual reproduction, mutation and dispersal. We found simulated time dependence of speciation rates, species-area relationships and species abundance distributions consistent with the behaviours found in nature. From our results, we predict steady speciation rates, more species in one-dimensional environments than two-dimensional environments, three scaling regimes of species-area relationships and lognormal distributions of species abundance with an excess of rare species and a tail that may be approximated by Fisher's logarithmic series. These are consistent with dependences reported for, among others, global birds and flowering plants, marine invertebrate fossils, ray-finned fishes, British birds and moths, North American songbirds, mammal fossils from Kansas and Panamanian shrubs. Quantitative comparisons of specific cases are remarkably successful. Our biodiversity results provide additional evidence that species diversity arises without specific physical barriers. This is similar to heavy traffic flows, where traffic jams can form even without accidents or barriers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Aguiar, M A M -- Baranger, M -- Baptestini, E M -- Kaufman, L -- Bar-Yam, Y -- England -- Nature. 2009 Jul 16;460(7253):384-7. doi: 10.1038/nature08168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New England Complex Systems Institute, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19606148" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Disorders of Sex Development ; Extinction, Biological ; *Genetic Speciation ; Genotype ; Haploidy ; Models, Biological ; Mutation/genetics ; Population Dynamics ; Reproduction/genetics/*physiology ; Sexual Behavior, Animal ; Time Factors
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  • 26
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rose, Steven -- England -- Nature. 2009 Nov 5;462(7269):35. doi: 10.1038/462035c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890309" target="_blank"〉PubMed〈/a〉
    Keywords: Continental Population Groups/*genetics ; *Ethics, Research ; Female ; Humans ; Intelligence/*genetics ; Male ; Reproducibility of Results ; *Sex Characteristics
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  • 27
    Publication Date: 2009-09-18
    Description: Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance. Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172006/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, David L -- Thio, Chloe L -- Martin, Maureen P -- Qi, Ying -- Ge, Dongliang -- O'Huigin, Colm -- Kidd, Judith -- Kidd, Kenneth -- Khakoo, Salim I -- Alexander, Graeme -- Goedert, James J -- Kirk, Gregory D -- Donfield, Sharyne M -- Rosen, Hugo R -- Tobler, Leslie H -- Busch, Michael P -- McHutchison, John G -- Goldstein, David B -- Carrington, Mary -- HHSN261200800001E/CO/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 DA004334/DA/NIDA NIH HHS/ -- R01DA004334/DA/NIDA NIH HHS/ -- R01DA013324/DA/NIDA NIH HHS/ -- R01DK60590/DK/NIDDK NIH HHS/ -- R01HD41224/HD/NICHD NIH HHS/ -- R01HL076902/HL/NHLBI NIH HHS/ -- R56 DA004334/DA/NIDA NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2009 Oct 8;461(7265):798-801. doi: 10.1038/nature08463.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University, Division of Infectious Diseases, Baltimore, Maryland 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759533" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Africa/ethnology ; Europe/ethnology ; Female ; Gene Frequency ; Genetic Variation/*genetics ; Genome-Wide Association Study ; Genotype ; Hepacivirus/drug effects/*immunology/physiology ; Hepatitis C/drug therapy/*genetics/*immunology/virology ; Humans ; Interleukins/*genetics/*immunology ; Male ; Polymorphism, Single Nucleotide/genetics
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  • 28
    Publication Date: 2009-09-29
    Description: Sexual antagonism, or conflict between the sexes, has been proposed as a driving force in both sex-chromosome turnover and speciation. Although closely related species often have different sex-chromosome systems, it is unknown whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here we show that a newly evolved sex chromosome contains genes that contribute to speciation in threespine stickleback fish (Gasterosteus aculeatus). We first identified a neo-sex chromosome system found only in one member of a sympatric species pair in Japan. We then performed genetic linkage mapping of male-specific traits important for reproductive isolation between the Japanese species pair. The neo-X chromosome contains loci for male courtship display traits that contribute to behavioural isolation, whereas the ancestral X chromosome contains loci for both behavioural isolation and hybrid male sterility. Our work not only provides strong evidence for a large X-effect on reproductive isolation in a vertebrate system, but also provides direct evidence that a young neo-X chromosome contributes to reproductive isolation between closely related species. Our data indicate that sex-chromosome turnover might have a greater role in speciation than was previously appreciated.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776091/" 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/PMC2776091/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kitano, Jun -- Ross, Joseph A -- Mori, Seiichi -- Kume, Manabu -- Jones, Felicity C -- Chan, Yingguang F -- Absher, Devin M -- Grimwood, Jane -- Schmutz, Jeremy -- Myers, Richard M -- Kingsley, David M -- Peichel, Catherine L -- P50 HG002568/HG/NHGRI NIH HHS/ -- P50 HG002568-08/HG/NHGRI NIH HHS/ -- P50 HG02568/HG/NHGRI NIH HHS/ -- R01 GM071854/GM/NIGMS NIH HHS/ -- R01 GM071854-05/GM/NIGMS NIH HHS/ -- T32 GM07270/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Oct 22;461(7267):1079-83. doi: 10.1038/nature08441. Epub 2009 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19783981" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Size ; Crosses, Genetic ; Female ; *Genetic Speciation ; Hybridization, Genetic ; Infertility, Male/genetics ; Japan ; Male ; Mating Preference, Animal ; Oceans and Seas ; Pacific Ocean ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Reproduction/genetics/physiology ; Sex Characteristics ; Sex Chromosomes/*genetics ; Smegmamorpha/anatomy & histology/classification/*genetics/*physiology ; Social Isolation ; Y Chromosome/genetics
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  • 29
    Publication Date: 2009-05-09
    Description: Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498958/" 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/PMC3498958/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guan, Ji-Song -- Haggarty, Stephen J -- Giacometti, Emanuela -- Dannenberg, Jan-Hermen -- Joseph, Nadine -- Gao, Jun -- Nieland, Thomas J F -- Zhou, Ying -- Wang, Xinyu -- Mazitschek, Ralph -- Bradner, James E -- DePinho, Ronald A -- Jaenisch, Rudolf -- Tsai, Li-Huei -- R01 DA028301/DA/NIDA NIH HHS/ -- R01 DA028301-02/DA/NIDA NIH HHS/ -- R01 NS051874/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 May 7;459(7243):55-60. doi: 10.1038/nature07925.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19424149" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Butyrates/pharmacology ; Dendritic Spines/physiology ; Electrical Synapses/*physiology ; Female ; Gene Expression Regulation ; Hippocampus/metabolism ; Histone Deacetylase 1 ; Histone Deacetylase 2 ; Histone Deacetylase Inhibitors ; Histone Deacetylases/deficiency/genetics/*metabolism ; Hydroxamic Acids/pharmacology ; Learning/drug effects ; Male ; Memory/drug effects/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; Promoter Regions, Genetic/genetics ; Repressor Proteins/antagonists & inhibitors/genetics/*metabolism ; Sodium/pharmacology
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  • 30
    Publication Date: 2009-01-17
    Description: Autonomous and self-sustained oscillator circuits mediating the periodic induction of specific target genes are minimal genetic time-keeping devices found in the central and peripheral circadian clocks. They have attracted significant attention because of their intriguing dynamics and their importance in controlling critical repair, metabolic and signalling pathways. The precise molecular mechanism and expression dynamics of this mammalian circadian clock are still not fully understood. Here we describe a synthetic mammalian oscillator based on an auto-regulated sense-antisense transcription control circuit encoding a positive and a time-delayed negative feedback loop, enabling autonomous, self-sustained and tunable oscillatory gene expression. After detailed systems design with experimental analyses and mathematical modelling, we monitored oscillating concentrations of green fluorescent protein with tunable frequency and amplitude by time-lapse microscopy in real time in individual Chinese hamster ovary cells. The synthetic mammalian clock may provide an insight into the dynamics of natural periodic processes and foster advances in the design of prosthetic networks in future gene and cell therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tigges, Marcel -- Marquez-Lago, Tatiana T -- Stelling, Jorg -- Fussenegger, Martin -- England -- Nature. 2009 Jan 15;457(7227):309-12. doi: 10.1038/nature07616.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148099" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*physiology ; CHO Cells ; Circadian Rhythm/*physiology ; Cricetinae ; Cricetulus ; Feedback, Physiological ; Fluorescence ; Gene Expression Regulation/*genetics ; Genes, Synthetic/*genetics ; *Genetic Engineering ; Green Fluorescent Proteins/analysis/genetics/metabolism ; Models, Biological ; Reproducibility of Results ; Time Factors ; Transcription, Genetic
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  • 31
    Publication Date: 2009-08-13
    Description: Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Xiao-yang -- Li, Wei -- Lv, Zhuo -- Liu, Lei -- Tong, Man -- Hai, Tang -- Hao, Jie -- Guo, Chang-long -- Ma, Qing-wen -- Wang, Liu -- Zeng, Fanyi -- Zhou, Qi -- England -- Nature. 2009 Sep 3;461(7260):86-90. doi: 10.1038/nature08267.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19672241" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/cytology/physiology ; Cell Dedifferentiation/physiology ; Cell Line ; Cell Lineage ; Cellular Reprogramming ; Embryo, Mammalian/cytology/embryology/metabolism ; Embryonic Stem Cells/cytology/physiology ; Female ; Fibroblasts/cytology ; Gene Expression Profiling ; Genetic Complementation Test ; Male ; Mice ; Mice, SCID ; Pluripotent Stem Cells/cytology/*physiology ; *Polyploidy ; Pregnancy ; *Reproductive Techniques ; Survival Rate ; Teratoma
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  • 32
    Publication Date: 2009-12-17
    Description: Male animals are typically more elaborately ornamented than females. Classic sexual selection theory notes that because sperm are cheaper to produce than eggs, and because males generally compete more intensely for reproductive opportunities and invest less in parental care than females, males can obtain greater fitness benefits from mating multiply. Therefore, sexual selection typically results in male-biased sex differences in secondary sexual characters. This generality has recently been questioned, because in cooperatively breeding vertebrates, the strength of selection on traits used in intrasexual competition for access to mates (sexual selection) or other resources linked to reproduction (social selection) is similar in males and females. Because selection is acting with comparable intensity in both sexes in cooperatively breeding species, the degree of sexual dimorphism in traits used in intrasexual competition should be reduced in cooperative breeders. Here we use the socially diverse African starlings (Sturnidae) to demonstrate that the degree of sexual dimorphism in plumage and body size is reduced in cooperatively breeding species as a result of increased selection on females for traits that increase access to reproductive opportunities, other resources, or higher social status. In cooperative breeders such as these, where there is unequal sharing of reproduction (reproductive skew) among females, and where female dominance rank influences access to mates and other resources, intrasexual competition among females may be intense and ultimately select for female trait elaboration. Selection is thereby acting with different intensities on males and females in cooperatively versus non-cooperatively breeding species, and female-female interactions in group-living vertebrates will have important consequences for the evolution of female morphological, physiological and behavioural traits.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rubenstein, Dustin R -- Lovette, Irby J -- England -- Nature. 2009 Dec 10;462(7274):786-9. doi: 10.1038/nature08614.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Columbia University, Department of Ecology, Evolution and Environmental Biology, 10th Floor Schermerhorn Extension, 1200 Amsterdam Avenue, New York, New York 10027, USA. dr2497@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010686" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; Bayes Theorem ; Body Size/physiology ; Competitive Behavior ; Cooperative Behavior ; Feathers/anatomy & histology/physiology ; Female ; Male ; Markov Chains ; Mating Preference, Animal/*physiology ; Monte Carlo Method ; Phylogeny ; Reproduction/*physiology ; Selection, Genetic ; *Sex Characteristics ; *Social Behavior ; Social Dominance ; Starlings/*anatomy & histology/*physiology ; Wings, Animal/anatomy & histology
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  • 33
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Jan 15;457(7227):236. doi: 10.1038/457236a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148049" target="_blank"〉PubMed〈/a〉
    Keywords: *Acquired Immunodeficiency Syndrome/drug ; therapy/economics/epidemiology/prevention & control ; *Federal Government ; Female ; Humans ; International Cooperation ; *Leadership ; Male ; Sexual Abstinence ; United States/epidemiology
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  • 34
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Todes, Daniel -- England -- Nature. 2009 Nov 5;462(7269):36-7. doi: 10.1038/462036a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of the History of Medicine at Johns Hopkins University, 1900 East Monument Street, Baltimore, Maryland 21205, USA. dtodes@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890312" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Biological Science Disciplines/*history ; *Competitive Behavior ; Cooperative Behavior ; *Cultural Diversity ; Food Supply ; Great Britain ; History, 19th Century ; History, 20th Century ; Humans ; Literature, Modern/history ; Metaphor ; Models, Biological ; Population Density ; Russia ; Selection, Genetic
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  • 35
    Publication Date: 2009-12-18
    Description: Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746295/" 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/PMC3746295/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Augustine -- Steinthorsdottir, Valgerdur -- Masson, Gisli -- Thorleifsson, Gudmar -- Sulem, Patrick -- Besenbacher, Soren -- Jonasdottir, Aslaug -- Sigurdsson, Asgeir -- Kristinsson, Kari Th -- Jonasdottir, Adalbjorg -- Frigge, Michael L -- Gylfason, Arnaldur -- Olason, Pall I -- Gudjonsson, Sigurjon A -- Sverrisson, Sverrir -- Stacey, Simon N -- Sigurgeirsson, Bardur -- Benediktsdottir, Kristrun R -- Sigurdsson, Helgi -- Jonsson, Thorvaldur -- Benediktsson, Rafn -- Olafsson, Jon H -- Johannsson, Oskar Th -- Hreidarsson, Astradur B -- Sigurdsson, Gunnar -- DIAGRAM Consortium -- Ferguson-Smith, Anne C -- Gudbjartsson, Daniel F -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- 077016/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- G9723500/Medical Research Council/United Kingdom -- K08 AR055688/AR/NIAMS NIH HHS/ -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106179474/Medical Research Council/United Kingdom -- MC_U127592696/Medical Research Council/United Kingdom -- R01 DK029867/DK/NIDDK NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):868-74. doi: 10.1038/nature08625.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. kong@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016592" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Binding Sites ; Breast Neoplasms/genetics ; Carcinoma, Basal Cell/genetics ; Chromosomes, Human, Pair 11/genetics ; Chromosomes, Human, Pair 7/genetics ; DNA Methylation/genetics ; Diabetes Mellitus, Type 2/genetics ; *Fathers ; Female ; Genetic Predisposition to Disease/*genetics ; Genome, Human/genetics ; Genomic Imprinting/genetics ; Haplotypes ; Humans ; Iceland ; Male ; *Mothers ; Pedigree ; Polymorphism, Single Nucleotide/*genetics ; Repressor Proteins/metabolism
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  • 36
    Publication Date: 2009-02-06
    Description: The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778612/" 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/PMC2778612/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diehn, Maximilian -- Cho, Robert W -- Lobo, Neethan A -- Kalisky, Tomer -- Dorie, Mary Jo -- Kulp, Angela N -- Qian, Dalong -- Lam, Jessica S -- Ailles, Laurie E -- Wong, Manzhi -- Joshua, Benzion -- Kaplan, Michael J -- Wapnir, Irene -- Dirbas, Frederick M -- Somlo, George -- Garberoglio, Carlos -- Paz, Benjamin -- Shen, Jeannie -- Lau, Sean K -- Quake, Stephen R -- Brown, J Martin -- Weissman, Irving L -- Clarke, Michael F -- R01 CA100225/CA/NCI NIH HHS/ -- R01 CA100225-05/CA/NCI NIH HHS/ -- U54 CA126524/CA/NCI NIH HHS/ -- U54 CA126524-04/CA/NCI NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):780-3. doi: 10.1038/nature07733.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, 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/19194462" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/physiopathology ; Cells, Cultured ; DNA Damage/genetics/radiation effects ; Female ; Gene Expression ; Humans ; Mammary Glands, Human/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/*metabolism/*radiation effects ; Radiation Tolerance/*physiology ; Reactive Oxygen Species/*metabolism
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  • 37
    Publication Date: 2009-10-09
    Description: PIWI-interacting RNAs (piRNAs) silence retrotransposons in Drosophila germ lines by associating with the PIWI proteins Argonaute 3 (AGO3), Aubergine (Aub) and Piwi. piRNAs in Drosophila are produced from intergenic repetitive genes and piRNA clusters by two systems: the primary processing pathway and the amplification loop. The amplification loop occurs in a Dicer-independent, PIWI-Slicer-dependent manner. However, primary piRNA processing remains elusive. Here we analysed piRNA processing in a Drosophila ovarian somatic cell line where Piwi, but not Aub or AGO3, is expressed; thus, only the primary piRNAs exist. In addition to flamenco, a Piwi-specific piRNA cluster, traffic jam (tj), a large Maf gene, was determined as a new piRNA cluster. piRNAs arising from tj correspond to the untranslated regions of tj messenger RNA and are sense-oriented. piRNA loading on to Piwi may occur in the cytoplasm. zucchini, a gene encoding a putative cytoplasmic nuclease, is required for tj-derived piRNA production. In tj and piwi mutant ovaries, somatic cells fail to intermingle with germ cells and Fasciclin III is overexpressed. Loss of tj abolishes Piwi expression in gonadal somatic cells. Thus, in gonadal somatic cells, tj gives rise simultaneously to two different molecules: the TJ protein, which activates Piwi expression, and piRNAs, which define the Piwi targets for silencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saito, Kuniaki -- Inagaki, Sachi -- Mituyama, Toutai -- Kawamura, Yoshinori -- Ono, Yukiteru -- Sakota, Eri -- Kotani, Hazuki -- Asai, Kiyoshi -- Siomi, Haruhiko -- Siomi, Mikiko C -- England -- Nature. 2009 Oct 29;461(7268):1296-9. doi: 10.1038/nature08501. Epub 2009 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Keio University School of Medicine, Tokyo 160-8582, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812547" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Cell Adhesion Molecules, Neuronal/metabolism ; Cell Line ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Endoribonucleases/metabolism ; Female ; Genes, Insect/genetics ; Genetic Loci/genetics ; Maf Transcription Factors, Large/genetics/*metabolism ; Male ; Ovary/cytology/metabolism ; Phenotype ; Proto-Oncogene Proteins/genetics/*metabolism ; RNA/biosynthesis/genetics/*metabolism ; RNA Interference ; RNA Processing, Post-Transcriptional ; RNA-Induced Silencing Complex/genetics/*metabolism ; Testis/cytology/metabolism
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  • 38
    Publication Date: 2009-04-17
    Description: During cell division microtubules capture chromosomes by binding to the kinetochore assembled in the centromeric region of chromosomes. In mitosis sister chromatids are captured by microtubules emanating from both spindle poles, a process called bipolar attachment, whereas in meiosis I sisters are attached to microtubules originating from one spindle pole, called monopolar attachment. For determining chromosome orientation, kinetochore geometry or structure might be an important target of regulation. However, the molecular basis of this regulation has remained elusive. Here we show the link between kinetochore orientation and cohesion within the centromere in fission yeast Schizosaccharomyces pombe by strategies developed to visualize the concealed cohesion within the centromere, and to introduce artificial tethers that can influence kinetochore geometry. Our data imply that cohesion at the core centromere induces the mono-orientation of kinetochores whereas cohesion at the peri-centromeric region promotes bi-orientation. Our study may reveal a general mechanism for the geometric regulation of kinetochores, which collaborates with previously defined tension-dependent reorientation machinery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakuno, Takeshi -- Tada, Kenji -- Watanabe, Yoshinori -- England -- Nature. 2009 Apr 16;458(7240):852-8. doi: 10.1038/nature07876.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19370027" target="_blank"〉PubMed〈/a〉
    Keywords: Centromere/genetics/*metabolism ; Chromosome Segregation ; Kinetochores/*metabolism ; Meiosis ; Microtubules/metabolism ; Mitosis ; Models, Biological ; Schizosaccharomyces/*cytology
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  • 39
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolgin, Elie -- England -- Nature. 2009 Dec 17;462(7275):843-5. doi: 10.1038/462843a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016572" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Genome, Human/*genetics ; History, 20th Century ; History, 21st Century ; *Human Genome Project/history ; Humans ; Male ; Reproducibility of Results ; Research Design ; *Research Personnel ; Research Subjects
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  • 40
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbondanzieri, Elio A -- Zhuang, Xiaowei -- England -- Nature. 2009 Jan 22;457(7228):392-3. doi: 10.1038/457392a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158782" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*chemistry/*metabolism ; Bacillus Phages/*enzymology ; DNA, Viral/chemistry/metabolism ; Hydrolysis ; Models, Biological ; Protein Structure, Quaternary ; Protein Subunits/chemistry/metabolism ; Virus Assembly
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  • 41
    Publication Date: 2009-07-22
    Description: Acquired uniparental disomy (aUPD) is a common feature of cancer genomes, leading to loss of heterozygosity. aUPD is associated not only with loss-of-function mutations of tumour suppressor genes, but also with gain-of-function mutations of proto-oncogenes. Here we show unique gain-of-function mutations of the C-CBL (also known as CBL) tumour suppressor that are tightly associated with aUPD of the 11q arm in myeloid neoplasms showing myeloproliferative features. The C-CBL proto-oncogene, a cellular homologue of v-Cbl, encodes an E3 ubiquitin ligase and negatively regulates signal transduction of tyrosine kinases. Homozygous C-CBL mutations were found in most 11q-aUPD-positive myeloid malignancies. Although the C-CBL mutations were oncogenic in NIH3T3 cells, c-Cbl was shown to functionally and genetically act as a tumour suppressor. C-CBL mutants did not have E3 ubiquitin ligase activity, but inhibited that of wild-type C-CBL and CBL-B (also known as CBLB), leading to prolonged activation of tyrosine kinases after cytokine stimulation. c-Cbl(-/-) haematopoietic stem/progenitor cells (HSPCs) showed enhanced sensitivity to a variety of cytokines compared to c-Cbl(+/+) HSPCs, and transduction of C-CBL mutants into c-Cbl(-/-) HSPCs further augmented their sensitivities to a broader spectrum of cytokines, including stem-cell factor (SCF, also known as KITLG), thrombopoietin (TPO, also known as THPO), IL3 and FLT3 ligand (FLT3LG), indicating the presence of a gain-of-function that could not be attributed to a simple loss-of-function. The gain-of-function effects of C-CBL mutants on cytokine sensitivity of HSPCs largely disappeared in a c-Cbl(+/+) background or by co-transduction of wild-type C-CBL, which suggests the pathogenic importance of loss of wild-type C-CBL alleles found in most cases of C-CBL-mutated myeloid neoplasms. Our findings provide a new insight into a role of gain-of-function mutations of a tumour suppressor associated with aUPD in the pathogenesis of some myeloid cancer subsets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanada, Masashi -- Suzuki, Takahiro -- Shih, Lee-Yung -- Otsu, Makoto -- Kato, Motohiro -- Yamazaki, Satoshi -- Tamura, Azusa -- Honda, Hiroaki -- Sakata-Yanagimoto, Mamiko -- Kumano, Keiki -- Oda, Hideaki -- Yamagata, Tetsuya -- Takita, Junko -- Gotoh, Noriko -- Nakazaki, Kumi -- Kawamata, Norihiko -- Onodera, Masafumi -- Nobuyoshi, Masaharu -- Hayashi, Yasuhide -- Harada, Hiroshi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Hiraku -- Ozawa, Keiya -- Omine, Mitsuhiro -- Hirai, Hisamaru -- Nakauchi, Hiromitsu -- Koeffler, H Phillip -- Ogawa, Seishi -- 2R01CA026038-30/CA/NCI NIH HHS/ -- England -- Nature. 2009 Aug 13;460(7257):904-8. doi: 10.1038/nature08240. Epub 2009 Jul 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19620960" target="_blank"〉PubMed〈/a〉
    Keywords: Allelic Imbalance ; Amino Acid Sequence ; Animals ; Base Sequence ; Chromosomes, Human, Pair 11/genetics ; Female ; *Genes, Tumor Suppressor ; Humans ; Leukemia, Myeloid/*genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/chemistry/genetics/*metabolism ; Mutation ; NIH 3T3 Cells ; Neoplasm Transplantation ; Oncogenes/genetics ; Phosphorylation ; Protein Conformation ; Proto-Oncogene Proteins c-cbl/antagonists & ; inhibitors/chemistry/deficiency/*genetics/*metabolism ; Ubiquitination ; Uniparental Disomy/genetics ; ras Proteins/genetics/metabolism
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  • 42
    Publication Date: 2009-11-27
    Description: Receptor-activator of NF-kappaB ligand (TNFSF11, also known as RANKL, OPGL, TRANCE and ODF) and its tumour necrosis factor (TNF)-family receptor RANK are essential regulators of bone remodelling, lymph node organogenesis and formation of a lactating mammary gland. RANKL and RANK are also expressed in the central nervous system. However, the functional relevance of RANKL/RANK in the brain was entirely unknown. Here we report that RANKL and RANK have an essential role in the brain. In both mice and rats, central RANKL injections trigger severe fever. Using tissue-specific Nestin-Cre and GFAP-Cre rank(floxed) deleter mice, the function of RANK in the fever response was genetically mapped to astrocytes. Importantly, Nestin-Cre and GFAP-Cre rank(floxed) deleter mice are resistant to lipopolysaccharide-induced fever as well as fever in response to the key inflammatory cytokines IL-1beta and TNFalpha. Mechanistically, RANKL activates brain regions involved in thermoregulation and induces fever via the COX2-PGE(2)/EP3R pathway. Moreover, female Nestin-Cre and GFAP-Cre rank(floxed) mice exhibit increased basal body temperatures, suggesting that RANKL and RANK control thermoregulation during normal female physiology. We also show that two children with RANK mutations exhibit impaired fever during pneumonia. These data identify an entirely novel and unexpected function for the key osteoclast differentiation factors RANKL/RANK in female thermoregulation and the central fever response in inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanada, Reiko -- Leibbrandt, Andreas -- Hanada, Toshikatsu -- Kitaoka, Shiho -- Furuyashiki, Tomoyuki -- Fujihara, Hiroaki -- Trichereau, Jean -- Paolino, Magdalena -- Qadri, Fatimunnisa -- Plehm, Ralph -- Klaere, Steffen -- Komnenovic, Vukoslav -- Mimata, Hiromitsu -- Yoshimatsu, Hironobu -- Takahashi, Naoyuki -- von Haeseler, Arndt -- Bader, Michael -- Kilic, Sara Sebnem -- Ueta, Yoichi -- Pifl, Christian -- Narumiya, Shuh -- Penninger, Josef M -- England -- Nature. 2009 Nov 26;462(7272):505-9. doi: 10.1038/nature08596.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940926" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/drug effects/metabolism ; Body Temperature Regulation/*drug effects/*physiology ; Child ; Dinoprostone/metabolism ; Female ; Fever/*chemically induced/complications/*metabolism ; Gene Expression Profiling ; Humans ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred C57BL ; Pneumonia/complications/metabolism ; RANK Ligand/administration & dosage/antagonists & ; inhibitors/metabolism/*pharmacology ; Rats ; Rats, Wistar ; Receptor Activator of Nuclear Factor-kappa B/genetics/*metabolism ; Receptors, Prostaglandin E/metabolism ; Receptors, Prostaglandin E, EP3 Subtype ; *Sex Characteristics
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  • 43
    Publication Date: 2009-06-19
    Description: Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes. Somatic XCI is regulated by homologous X-chromosome pairing and counting, and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled, as blocking one process compromises the other and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation. Recent evidence suggests coupling of Xist expression to pluripotency factors occurs, but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1) lies at the top of the XCI hierarchy, and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory noncoding RNA genes of the X-inactivation centre, and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein-protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057664/" 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/PMC3057664/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Donohoe, Mary E -- Silva, Susana S -- Pinter, Stefan F -- Xu, Na -- Lee, Jeannie T -- GM58839/GM/NIGMS NIH HHS/ -- R01 GM058839/GM/NIGMS NIH HHS/ -- R01 GM058839-10/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 2;460(7251):128-32. doi: 10.1038/nature08098. Epub 2009 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Chromosome Pairing ; Female ; Humans ; Male ; Mice ; Octamer Transcription Factor-3/deficiency/genetics/*metabolism ; Protein Binding ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; Repressor Proteins/*metabolism ; SOXB1 Transcription Factors ; Transcriptional Activation ; X Chromosome/*genetics/*metabolism ; X Chromosome Inactivation/*genetics ; YY1 Transcription Factor/metabolism
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  • 44
    Publication Date: 2009-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muller-Landau, Helene C -- England -- Nature. 2009 Feb 19;457(7232):969-70. doi: 10.1038/457969a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225510" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Atmosphere/chemistry ; Biomass ; Carbon/analysis/*metabolism ; Carbon Dioxide/analysis/metabolism ; Models, Biological ; Trees/chemistry/growth & development/*metabolism ; *Tropical Climate ; Wilderness
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  • 45
    Publication Date: 2009-01-20
    Description: The computational power of single neurons is greatly enhanced by active dendritic conductances that have a large influence on their spike activity. In cortical output neurons such as the large pyramidal cells of layer 5 (L5), activation of apical dendritic calcium channels leads to plateau potentials that increase the gain of the input/output function and switch the cell to burst-firing mode. The apical dendrites are innervated by local excitatory and inhibitory inputs as well as thalamic and corticocortical projections, which makes it a formidable task to predict how these inputs influence active dendritic properties in vivo. Here we investigate activity in populations of L5 pyramidal dendrites of the somatosensory cortex in awake and anaesthetized rats following sensory stimulation using a new fibre-optic method for recording dendritic calcium changes. We show that the strength of sensory stimulation is encoded in the combined dendritic calcium response of a local population of L5 pyramidal cells in a graded manner. The slope of the stimulus-response function was under the control of a particular subset of inhibitory neurons activated by synaptic inputs predominantly in L5. Recordings from single apical tuft dendrites in vitro showed that activity in L5 pyramidal neurons disynaptically coupled via interneurons directly blocks the initiation of dendritic calcium spikes in neighbouring pyramidal neurons. The results constitute a functional description of a cortical microcircuit in awake animals that relies on the active properties of L5 pyramidal dendrites and their very high sensitivity to inhibition. The microcircuit is organized so that local populations of apical dendrites can adaptively encode bottom-up sensory stimuli linearly across their full dynamic range.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murayama, Masanori -- Perez-Garci, Enrique -- Nevian, Thomas -- Bock, Tobias -- Senn, Walter -- Larkum, Matthew E -- England -- Nature. 2009 Feb 26;457(7233):1137-41. doi: 10.1038/nature07663. Epub 2009 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Physiologisches Institut, Universitat Bern, Buhlplatz 5, CH-3012 Bern, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19151696" target="_blank"〉PubMed〈/a〉
    Keywords: Anesthesia ; Animals ; Calcium/metabolism ; Dendrites/*physiology ; Electric Stimulation ; Excitatory Postsynaptic Potentials/physiology ; Female ; Interneurons/*physiology ; Models, Neurological ; Rats ; Rats, Wistar ; Somatosensory Cortex/*cytology/*physiology ; Wakefulness/physiology
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  • 46
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    Nature Publishing Group (NPG)
    Publication Date: 2009-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanderson, Katharine -- England -- Nature. 2009 Mar 19;458(7236):269. doi: 10.1038/458269a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295573" target="_blank"〉PubMed〈/a〉
    Keywords: Clinical Trials, Phase I as Topic ; Cyclohexanols/chemistry/economics/pharmacokinetics ; Deuterium/*chemistry ; Drug Industry/*economics ; Female ; Humans ; Paroxetine/analogs & derivatives/chemistry/economics/pharmacokinetics ; Patents as Topic/legislation & jurisprudence ; Pharmaceutical Preparations/*chemistry/economics/*metabolism ; Venlafaxine Hydrochloride
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  • 47
    Publication Date: 2009-08-08
    Description: During the twentieth century, the global population has gone through unprecedented increases in economic and social development that coincided with substantial declines in human fertility and population growth rates. The negative association of fertility with economic and social development has therefore become one of the most solidly established and generally accepted empirical regularities in the social sciences. As a result of this close connection between development and fertility decline, more than half of the global population now lives in regions with below-replacement fertility (less than 2.1 children per woman). In many highly developed countries, the trend towards low fertility has also been deemed irreversible. Rapid population ageing, and in some cases the prospect of significant population decline, have therefore become a central socioeconomic concern and policy challenge. Here we show, using new cross-sectional and longitudinal analyses of the total fertility rate and the human development index (HDI), a fundamental change in the well-established negative relationship between fertility and development as the global population entered the twenty-first century. Although development continues to promote fertility decline at low and medium HDI levels, our analyses show that at advanced HDI levels, further development can reverse the declining trend in fertility. The previously negative development-fertility relationship has become J-shaped, with the HDI being positively associated with fertility among highly developed countries. This reversal of fertility decline as a result of continued economic and social development has the potential to slow the rates of population ageing, thereby ameliorating the social and economic problems that have been associated with the emergence and persistence of very low fertility.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myrskyla, Mikko -- Kohler, Hans-Peter -- Billari, Francesco C -- England -- Nature. 2009 Aug 6;460(7256):741-3. doi: 10.1038/nature08230.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Population Studies Center, University of Pennsylvania, 3718 Locust Walk, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661915" target="_blank"〉PubMed〈/a〉
    Keywords: Age Distribution ; *Birth Rate/trends ; Cross-Sectional Studies ; Developed Countries/economics/*statistics & numerical data ; Education ; Female ; Fertility/physiology ; History, 20th Century ; History, 21st Century ; Humans ; Income ; Life Expectancy ; Longitudinal Studies ; Male ; Maternal Age ; *Population Growth ; Reproductive Behavior/history/*statistics & numerical data ; Technology/history/statistics & numerical data/trends
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  • 48
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuroiwa, Asato -- England -- Nature. 2009 Nov 5;462(7269):34. doi: 10.1038/462034b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avian Proteins/genetics ; Chick Embryo ; Chickens/*genetics ; Female ; Humans ; Male ; *Models, Biological ; Sex Chromosomes/genetics ; *Sex Determination Processes ; Testis/embryology/metabolism ; Transcription Factors/*genetics
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  • 49
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    Nature Publishing Group (NPG)
    Publication Date: 2009-02-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tonzani, Stefano -- England -- Nature. 2009 Feb 19;457(7232):974. doi: 10.1038/457974a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225516" target="_blank"〉PubMed〈/a〉
    Keywords: Colloids/*chemistry ; *Magnetics ; Models, Biological ; Nanostructures/chemistry/ultrastructure ; Particle Size ; Water/chemistry
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  • 50
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kutschera, U -- England -- Nature. 2009 Apr 23;458(7241):967. doi: 10.1038/458967c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396120" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; *Competitive Behavior ; Cooperative Behavior ; History, 19th Century ; Models, Biological ; *Selection, Genetic ; *Translating ; *Translations
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  • 51
    Publication Date: 2009-11-10
    Description: CD4(+) T helper cells are well known for their role in providing critical signals during priming of cytotoxic CD8(+) T lymphocyte (CTL) responses in vivo. T-cell help is required for the generation of primary CTL responses as well as in promoting protective CD8(+) memory T-cell development. However, the role of CD4 help in the control of CTL responses at the effector stage is unknown. Here we show that fully helped effector CTLs are themselves not self-sufficient for entry into the infected tissue, but rely on the CD4(+) T cells to provide the necessary cue. CD4(+) T helper cells control the migration of CTL indirectly through the secretion of IFN-gamma and induction of local chemokine secretion in the infected tissue. Our results reveal a previously unappreciated role of CD4 help in mobilizing effector CTL to the peripheral sites of infection where they help to eliminate infected cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789415/" 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/PMC2789415/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakanishi, Yusuke -- Lu, Bao -- Gerard, Craig -- Iwasaki, Akiko -- AI054359/AI/NIAID NIH HHS/ -- AI062428/AI/NIAID NIH HHS/ -- AI39759/AI/NIAID NIH HHS/ -- HL51366/HL/NHLBI NIH HHS/ -- R01 AI054359/AI/NIAID NIH HHS/ -- R01 AI054359-06A2/AI/NIAID NIH HHS/ -- R01 AI062428/AI/NIAID NIH HHS/ -- R01 AI062428-05/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Nov 26;462(7272):510-3. doi: 10.1038/nature08511. Epub 2009 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, 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/19898495" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Chemokines/immunology/secretion ; *Chemotaxis ; Female ; Herpes Simplex/immunology/virology ; Herpesvirus 2, Human/*immunology ; Immunity, Mucosal/immunology ; Interferon-gamma/antagonists & inhibitors/immunology/secretion ; Mice ; Mice, Inbred C57BL ; Models, Immunological ; Mucous Membrane/immunology/virology ; Receptors, CXCR3/metabolism ; T-Lymphocytes, Cytotoxic/*cytology/*immunology ; T-Lymphocytes, Helper-Inducer/*immunology/secretion ; Vagina/*immunology/*virology
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  • 52
    Publication Date: 2009-10-16
    Description: Language is a uniquely human ability that evolved at some point in the roughly 6,000,000 years since human and chimpanzee lines diverged. Even in the most linguistically impoverished environments, children naturally develop sophisticated language systems. In contrast, reading is a learnt skill that does not develop without intensive tuition and practice. Learning to read is likely to involve ontogenic structural brain changes, but these are nearly impossible to isolate in children owing to concurrent biological, environmental and social maturational changes. In Colombia, guerrillas are re-integrating into mainstream society and learning to read for the first time as adults. This presents a unique opportunity to investigate how literacy changes the brain, without the maturational complications present in children. Here we compare structural brain scans from those who learnt to read as adults (late-literates) with those from a carefully matched set of illiterates. Late-literates had more white matter in the splenium of the corpus callosum and more grey matter in bilateral angular, dorsal occipital, middle temporal, left supramarginal and superior temporal gyri. The importance of these brain regions for skilled reading was investigated in early literates, who learnt to read as children. We found anatomical connections linking the left and right angular and dorsal occipital gyri through the area of the corpus callosum where white matter was higher in late-literates than in illiterates; that reading, relative to object naming, increased the interhemispheric functional connectivity between the left and right angular gyri; and that activation in the left angular gyrus exerts top-down modulation on information flow from the left dorsal occipital gyrus to the left supramarginal gyrus. These findings demonstrate how the regions identified in late-literates interact during reading, relative to object naming, in early literates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carreiras, Manuel -- Seghier, Mohamed L -- Baquero, Silvia -- Estevez, Adelina -- Lozano, Alfonso -- Devlin, Joseph T -- Price, Cathy J -- 082420/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Oct 15;461(7266):983-6. doi: 10.1038/nature08461.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Basque Center on Cognition Brain and Language, Donostia-San Sebastian 20009, Spain [2] IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Spain. m.carreiras@bcbl.eu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829380" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Brain/*anatomy & histology/*physiology ; Child ; Colombia ; Corpus Callosum/anatomy & histology/physiology ; Educational Status ; Female ; Humans ; Language ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Models, Neurological ; Neural Pathways/physiology ; *Reading ; Speech/physiology ; Young Adult
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  • 53
    Publication Date: 2009-12-17
    Description: The majority of excitatory synapses in the mammalian CNS (central nervous system) are formed on dendritic spines, and spine morphology and distribution are critical for synaptic transmission, synaptic integration and plasticity. Here, we show that a secreted semaphorin, Sema3F, is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F, and its holoreceptor components neuropilin-2 (Npn-2, also known as Nrp2) and plexin A3 (PlexA3, also known as Plxna3), exhibit increased dentate gyrus (DG) granule cell (GC) and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn-2(-/-) brain slices cortical layer V and DG GCs exhibit increased mEPSC (miniature excitatory postsynaptic current) frequency. In contrast, a distinct Sema3A-Npn-1/PlexA4 signalling cascade controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. These disparate effects of secreted semaphorins are reflected in the restricted dendritic localization of Npn-2 to apical dendrites and of Npn-1 (also known as Nrp1) to all dendrites of cortical pyramidal neurons. Therefore, Sema3F signalling controls spine distribution along select dendritic processes, and distinct secreted semaphorin signalling events orchestrate CNS connectivity through the differential control of spine morphogenesis, synapse formation, and the elaboration of dendritic morphology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842559/" 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/PMC2842559/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tran, Tracy S -- Rubio, Maria E -- Clem, Roger L -- Johnson, Dontais -- Case, Lauren -- Tessier-Lavigne, Marc -- Huganir, Richard L -- Ginty, David D -- Kolodkin, Alex L -- F32 NS051003/NS/NINDS NIH HHS/ -- P50 MH06883/MH/NIMH NIH HHS/ -- R01 DC-006881/DC/NIDCD NIH HHS/ -- R01 MH059199/MH/NIMH NIH HHS/ -- R01 MH059199-07/MH/NIMH NIH HHS/ -- R01 MH059199-08/MH/NIMH NIH HHS/ -- R01 MH059199-09/MH/NIMH NIH HHS/ -- R01 MH059199-10/MH/NIMH NIH HHS/ -- R01 MH59199/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Dec 24;462(7276):1065-9. doi: 10.1038/nature08628. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, 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/20010807" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/cytology/drug effects/*growth & ; development/*metabolism/ultrastructure ; Female ; Gene Expression Regulation, Developmental ; Male ; Mice ; Mice, Knockout ; Neuropilin-1/metabolism ; Neuropilin-2/metabolism ; Pyramidal Cells/*cytology/drug effects/*growth & development/ultrastructure ; Recombinant Proteins/pharmacology ; Semaphorins/genetics/*metabolism/pharmacology ; Signal Transduction ; Synapses/drug effects/*physiology/ultrastructure
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  • 54
    Publication Date: 2009-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ehrenfeld, Joan G -- England -- Nature. 2009 Feb 26;457(7233):1079. doi: 10.1038/4571079d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242450" target="_blank"〉PubMed〈/a〉
    Keywords: Aphrodisiacs/*history ; *Drama ; England ; Female ; History, 16th Century ; Humans ; *Literature, Modern ; *Love ; Male ; Wit and Humor as Topic
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  • 55
    Publication Date: 2009-11-10
    Description: Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789972/" 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/PMC2789972/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Jacob -- Saha, Krishanu -- Pando, Bernardo -- van Zon, Jeroen -- Lengner, Christopher J -- Creyghton, Menno P -- van Oudenaarden, Alexander -- Jaenisch, Rudolf -- R01 CA087869/CA/NCI NIH HHS/ -- R01 CA087869-09/CA/NCI NIH HHS/ -- R01 HD045022/HD/NICHD NIH HHS/ -- R01 HD045022-06/HD/NICHD NIH HHS/ -- R01-CA087869/CA/NCI NIH HHS/ -- R01-HDO45022/PHS HHS/ -- R37 CA084198/CA/NCI NIH HHS/ -- R37 CA084198-09/CA/NCI NIH HHS/ -- R37-CA084198/CA/NCI NIH HHS/ -- U54CA143874/CA/NCI NIH HHS/ -- England -- Nature. 2009 Dec 3;462(7273):595-601. doi: 10.1038/nature08592. Epub 2009 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. Hanna@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19898493" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Division ; Cell Line ; *Cellular Reprogramming ; Gene Expression Regulation, Developmental ; Mice ; Mice, SCID ; Models, Biological ; Pluripotent Stem Cells/*cytology/*metabolism ; Time Factors ; Transcription Factors/genetics/metabolism
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  • 56
    Publication Date: 2009-05-15
    Description: Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41(+)c-Kit(+) haematopoietic progenitor cells, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782763/" 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/PMC2782763/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Adamo, Luigi -- Naveiras, Olaia -- Wenzel, Pamela L -- McKinney-Freeman, Shannon -- Mack, Peter J -- Gracia-Sancho, Jorge -- Suchy-Dicey, Astrid -- Yoshimoto, Momoko -- Lensch, M William -- Yoder, Mervin C -- Garcia-Cardena, Guillermo -- Daley, George Q -- R01 AI080759/AI/NIAID NIH HHS/ -- R01 AI080759-01/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 25;459(7250):1131-5. doi: 10.1038/nature08073. Epub 2009 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19440194" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta/cytology/embryology ; *Cell Differentiation ; Cell Line ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit/genetics ; Embryonic Stem Cells ; Endothelium-Dependent Relaxing Factors/pharmacology ; Female ; Gene Expression Regulation, Developmental ; Hematopoiesis/*physiology ; Hematopoietic Stem Cells/*cytology/drug effects ; Mice ; Nitric Oxide/pharmacology ; Pregnancy ; *Stress, Mechanical
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  • 57
    Publication Date: 2009-04-03
    Description: Explaining the ecological causes of evolutionary diversification is a major focus of biology, but surprisingly little has been said about the effects of evolutionary diversification on ecosystems. The number of species in an ecosystem and their traits are key predictors of many ecosystem-level processes, such as rates of productivity, biomass sequestration and decomposition. Here we demonstrate short-term ecosystem-level effects of adaptive radiation in the threespine stickleback (Gasterosteus aculeatus) over the past 10,000 years. These fish have undergone recent parallel diversification in several lakes in coastal British Columbia, resulting in the formation of two specialized species (benthic and limnetic) from a generalist ancestor. Using a mesocosm experiment, we demonstrate that this diversification has strong effects on ecosystems, affecting prey community structure, total primary production, and the nature of dissolved organic materials that regulate the spectral properties of light transmission in the system. However, these ecosystem effects do not simply increase in their relative strength with increasing specialization and species richness; instead, they reflect the complex and indirect consequences of ecosystem engineering by sticklebacks. It is well known that ecological factors influence adaptive radiation. We demonstrate that adaptive radiation, even over short timescales, can have profound effects on ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harmon, Luke J -- Matthews, Blake -- Des Roches, Simone -- Chase, Jonathan M -- Shurin, Jonathan B -- Schluter, Dolph -- England -- Nature. 2009 Apr 30;458(7242):1167-70. doi: 10.1038/nature07974. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of Idaho, Moscow, Idaho 83844-3051, USA. lukeh@uidaho.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339968" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; *Biological Evolution ; Biomass ; British Columbia ; *Ecosystem ; Fishes/*classification/*physiology ; Food Chain ; Fresh Water ; Genetic Speciation ; Models, Biological ; Population Density ; Predatory Behavior
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  • 58
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tuljapurkar, Shripad -- England -- Nature. 2009 Aug 6;460(7256):693-4. doi: 10.1038/460693a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661903" target="_blank"〉PubMed〈/a〉
    Keywords: Age Distribution ; *Birth Rate/trends ; Developed Countries/economics/*statistics & numerical data ; Education ; Female ; Fertility/physiology ; Humans ; Income ; Life Expectancy ; Male ; Maternal Age ; *Population Growth ; Reproductive Behavior/*statistics & numerical data
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  • 59
    Publication Date: 2009-07-10
    Description: Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786175/" 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/PMC2786175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harrison, David E -- Strong, Randy -- Sharp, Zelton Dave -- Nelson, James F -- Astle, Clinton M -- Flurkey, Kevin -- Nadon, Nancy L -- Wilkinson, J Erby -- Frenkel, Krystyna -- Carter, Christy S -- Pahor, Marco -- Javors, Martin A -- Fernandez, Elizabeth -- Miller, Richard A -- AG022303/AG/NIA NIH HHS/ -- AG022307/AG/NIA NIH HHS/ -- AG022308/AG/NIA NIH HHS/ -- AG025707/AG/NIA NIH HHS/ -- AG13319/AG/NIA NIH HHS/ -- P30 AG013319/AG/NIA NIH HHS/ -- P30 AG013319-119002/AG/NIA NIH HHS/ -- P30 AG013319-129002/AG/NIA NIH HHS/ -- P30 AG013319-139002/AG/NIA NIH HHS/ -- P30 AG013319-149002/AG/NIA NIH HHS/ -- P30 AG025707/AG/NIA NIH HHS/ -- U01 AG022303/AG/NIA NIH HHS/ -- U01 AG022307/AG/NIA NIH HHS/ -- U01 AG022307-01/AG/NIA NIH HHS/ -- U01 AG022307-02/AG/NIA NIH HHS/ -- U01 AG022307-03/AG/NIA NIH HHS/ -- U01 AG022307-04/AG/NIA NIH HHS/ -- U01 AG022307-05/AG/NIA NIH HHS/ -- U01 AG022307-05S1/AG/NIA NIH HHS/ -- U01 AG022308/AG/NIA NIH HHS/ -- England -- Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature08221. Epub 2009 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Jackson Laboratory, Bar Harbor, Maine 04609, USA. david.harrison@jax.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587680" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Aging/*drug effects/genetics/*physiology ; Animals ; Carrier Proteins/antagonists & inhibitors/metabolism ; Diet ; Disease Susceptibility ; Female ; Longevity/*drug effects/*genetics/physiology ; Male ; Mice ; Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/metabolism ; Sirolimus/*administration & dosage/*pharmacology ; Specific Pathogen-Free Organisms ; Survival Analysis ; TOR Serine-Threonine Kinases ; Time Factors
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  • 60
    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chakravarti, Aravinda -- England -- Nature. 2009 Sep 24;461(7263):487-8. doi: 10.1038/461487a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779444" target="_blank"〉PubMed〈/a〉
    Keywords: Asia/ethnology ; Continental Population Groups/genetics/history ; Ethnic Groups/*genetics/history ; Europe/ethnology ; Female ; Founder Effect ; Genetics, Population ; Genome, Human/genetics ; Genomics ; Genotype ; History, 16th Century ; History, 20th Century ; History, Ancient ; Humans ; India ; Language ; Male ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics
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  • 61
    Publication Date: 2009-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ng, Pauline C -- Murray, Sarah S -- Levy, Samuel -- Venter, J Craig -- England -- Nature. 2009 Oct 8;461(7265):724-6. doi: 10.1038/461724a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉J. Craig Venter Institute, Science Center Drive, San Diego, California 92121, USA. png@jcvi.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19812653" target="_blank"〉PubMed〈/a〉
    Keywords: Ethnic Groups/genetics ; False Negative Reactions ; Female ; Gene Frequency/genetics ; Genetic Counseling/methods/*standards ; Genetic Markers/genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Testing/methods/*standards ; Genetics, Medical/methods/*standards ; Genome, Human/*genetics ; Genome-Wide Association Study ; Genotype ; Health Behavior ; Humans ; Male ; Odds Ratio ; Pharmacogenetics ; *Practice Guidelines as Topic ; Prospective Studies ; Reproducibility of Results ; Sequence Analysis, DNA/standards
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  • 62
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    Nature Publishing Group (NPG)
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aguzzi, Adriano -- England -- Nature. 2009 Jun 18;459(7249):924-5. doi: 10.1038/459924a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536253" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/metabolism ; Animals ; Humans ; Models, Biological ; Peptides/metabolism ; Prion Diseases/*metabolism/pathology/transmission ; Prions/*chemistry/*metabolism ; Protein Denaturation ; tau Proteins/genetics/metabolism
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  • 63
    Publication Date: 2009-07-15
    Description: Recent finds demonstrate that internal fertilization and viviparity (live birth) were more widespread in the Placodermi, an extinct group of armoured fishes, than was previously realized. Placoderms represent the sister group of the crown group jawed vertebrates (Gnathostomata), making their mode(s) of reproduction potentially informative about primitive gnathostome conditions. An ossified pelvic fin basipterygium discovered in the arthrodire Incisoscutum ritchiei was hypothesized to be identical in males and females, with males presumed to have an additional cartilaginous element or series forming a clasper. Here we report the discovery of a completely ossified pelvic clasper in Incisoscutum ritchiei (WAM 03.3.28) which shows that this interpretation was incorrect: the basipterygium described previously is in fact unique to females. The male clasper is a slender rod attached to a square basal plate that articulates directly with the pelvis. It carries a small cap of dermal bone covered in denticles and small hooks that may be homologous with the much larger dermal component of the ptyctodont clasper.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahlberg, Per -- Trinajstic, Kate -- Johanson, Zerina -- Long, John -- England -- Nature. 2009 Aug 13;460(7257):888-9. doi: 10.1038/nature08176. Epub 2009 Jul 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Subdepartment of Evolutionary Organismal Biology, Department of Physiology and Developmental Biology, Uppsala University, Norbyvagen 18A, 752 36 Uppsala, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19597477" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Structures/anatomy & histology/*physiology ; Animals ; Female ; Fertilization/*physiology ; Fishes/*anatomy & histology/*physiology ; Fossils ; History, Ancient ; Male ; Pelvis/anatomy & histology ; Viviparity, Nonmammalian/physiology
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  • 64
    Publication Date: 2009-10-02
    Description: Down Syndrome cell adhesion molecule (Dscam) genes encode neuronal cell recognition proteins of the immunoglobulin superfamily. In Drosophila, Dscam1 generates 19,008 different ectodomains by alternative splicing of three exon clusters, each encoding half or a complete variable immunoglobulin domain. Identical isoforms bind to each other, but rarely to isoforms differing at any one of the variable immunoglobulin domains. Binding between isoforms on opposing membranes promotes repulsion. Isoform diversity provides the molecular basis for neurite self-avoidance. Self-avoidance refers to the tendency of branches from the same neuron (self-branches) to selectively avoid one another. To ensure that repulsion is restricted to self-branches, different neurons express different sets of isoforms in a biased stochastic fashion. Genetic studies demonstrated that Dscam1 diversity has a profound role in wiring the fly brain. Here we show how many isoforms are required to provide an identification system that prevents non-self branches from inappropriately recognizing each other. Using homologous recombination, we generated mutant animals encoding 12, 24, 576 and 1,152 potential isoforms. Mutant animals with deletions encoding 4,752 and 14,256 isoforms were also analysed. Branching phenotypes were assessed in three classes of neurons. Branching patterns improved as the potential number of isoforms increased, and this was independent of the identity of the isoforms. Although branching defects in animals with 1,152 potential isoforms remained substantial, animals with 4,752 isoforms were indistinguishable from wild-type controls. Mathematical modelling studies were consistent with the experimental results that thousands of isoforms are necessary to ensure acquisition of unique Dscam1 identities in many neurons. We conclude that thousands of isoforms are essential to provide neurons with a robust discrimination mechanism to distinguish between self and non-self during self-avoidance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836808/" 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/PMC2836808/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hattori, Daisuke -- Chen, Yi -- Matthews, Benjamin J -- Salwinski, Lukasz -- Sabatti, Chiara -- Grueber, Wesley B -- Zipursky, S Lawrence -- F31 NS060341/NS/NINDS NIH HHS/ -- R01 DC006485/DC/NIDCD NIH HHS/ -- R01 DC006485-07/DC/NIDCD NIH HHS/ -- R01 HD040279/HD/NICHD NIH HHS/ -- R01 HD040279-05/HD/NICHD NIH HHS/ -- T32 HD007430/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Oct 1;461(7264):644-8. doi: 10.1038/nature08431.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, 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/19794492" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Alternative Splicing ; Animals ; Brain/cytology/metabolism ; Cell Adhesion Molecules/*chemistry/genetics/*metabolism ; Drosophila Proteins/*chemistry/genetics/*metabolism ; Drosophila melanogaster/*cytology/genetics/*metabolism ; Female ; Male ; Models, Biological ; Mushroom Bodies/cytology/metabolism ; Neurites/*metabolism ; Protein Isoforms/chemistry/genetics/metabolism ; Sequence Deletion ; Stochastic Processes
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  • 65
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    Nature Publishing Group (NPG)
    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicholls, Henry -- England -- Nature. 2009 Sep 10;461(7261):164-6. doi: 10.1038/461164a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741680" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Developmental Biology ; Fossils ; Hagfishes/*anatomy & histology/*classification/embryology/genetics ; Head/anatomy & histology ; Humans ; Lampreys/*anatomy & histology/*classification/embryology/genetics ; MicroRNAs/genetics/metabolism ; Models, Biological ; Phylogeny ; Sharks/anatomy & histology/classification/embryology
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  • 66
    Publication Date: 2009-02-20
    Description: The assembly of complex structures out of simple colloidal building blocks is of practical interest for building materials with unique optical properties (for example photonic crystals and DNA biosensors) and is of fundamental importance in improving our understanding of self-assembly processes occurring on molecular to macroscopic length scales. Here we demonstrate a self-assembly principle that is capable of organizing a diverse set of colloidal particles into highly reproducible, rotationally symmetric arrangements. The structures are assembled using the magnetostatic interaction between effectively diamagnetic and paramagnetic particles within a magnetized ferrofluid. The resulting multipolar geometries resemble electrostatic charge configurations such as axial quadrupoles ('Saturn rings'), axial octupoles ('flowers'), linear quadrupoles (poles) and mixed multipole arrangements ('two tone'), which represent just a few examples of the type of structure that can be built using this technique.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Erb, Randall M -- Son, Hui S -- Samanta, Bappaditya -- Rotello, Vincent M -- Yellen, Benjamin B -- England -- Nature. 2009 Feb 19;457(7232):999-1002. doi: 10.1038/nature07766.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke University, Department of Mechanical Engineering and Materials Science, Center for Biologically Inspired Materials and Material Systems, Box 90300, Hudson Hall, Durham, North Carolina 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225522" target="_blank"〉PubMed〈/a〉
    Keywords: Colloids/*chemistry ; *Magnetics ; Microscopy, Electron, Scanning ; Microspheres ; Models, Biological ; Nanostructures/chemistry/ultrastructure ; Particle Size ; Water/chemistry
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2009-08-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2009 Aug 20;460(7258):940-1. doi: 10.1038/460940a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693052" target="_blank"〉PubMed〈/a〉
    Keywords: Anticoagulants/administration & dosage/adverse effects/therapeutic use ; Cardiovascular Diseases/*drug therapy/*genetics ; Clinical Trials as Topic ; Female ; Genetic Predisposition to Disease/*genetics ; Genetic Testing ; Genetic Variation ; Genome-Wide Association Study ; Genomics/trends ; Humans ; Pharmacogenetics/*trends ; Piperazines/administration & dosage/therapeutic use ; Platelet Aggregation Inhibitors/administration & dosage/adverse ; effects/therapeutic use ; Prasugrel Hydrochloride ; Thiophenes/administration & dosage/therapeutic use ; Ticlopidine/administration & dosage/adverse effects/analogs & ; derivatives/therapeutic use ; Warfarin/administration & dosage/adverse effects/therapeutic use
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  • 68
    Publication Date: 2009-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, Nicola J -- Barres, Ben A -- England -- Nature. 2009 Feb 5;457(7230):675-7. doi: 10.1038/457675a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194443" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/physiology ; Biological Evolution ; Brain/*cytology/embryology/pathology/*physiology ; Cell Communication ; Cell Lineage ; Homeostasis ; Humans ; Models, Biological ; Nerve Net/physiology ; Nervous System Diseases/pathology/physiopathology ; Neural Pathways/physiology ; Neuroglia/classification/cytology/pathology/*physiology ; Neurons/cytology/physiology ; Oligodendroglia/pathology/physiology ; Schwann Cells/pathology/physiology
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  • 69
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayden, Erika Check -- England -- Nature. 2009 Jan 15;457(7227):254-6. doi: 10.1038/457254a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148076" target="_blank"〉PubMed〈/a〉
    Keywords: *Federal Government ; Female ; *Global Health ; HIV Infections/*drug therapy/*economics/prevention & control ; Humans ; United States ; World Health Organization
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  • 70
    Publication Date: 2009-02-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2009 Feb 5;457(7230):642. doi: 10.1038/457642b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19205093" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cattle ; Cell Nucleus/metabolism ; Cellular Reprogramming/genetics/physiology ; Embryo, Mammalian/*cytology/*embryology ; Embryonic Stem Cells/*cytology ; Female ; Humans ; Mice ; *Nuclear Transfer Techniques ; Pluripotent Stem Cells/metabolism ; Rabbits ; Sheep ; Swine
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  • 71
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farmer, Stephen R -- England -- Nature. 2009 Apr 16;458(7240):839-40. doi: 10.1038/458839a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19370020" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, Brown/anatomy & histology/cytology/*metabolism ; *Cold Temperature ; Female ; Humans ; Male ; Obesity/drug therapy/*metabolism ; Sex Characteristics ; Weight Loss/*physiology
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  • 72
    Publication Date: 2009-08-21
    Description: The isolation of human induced pluripotent stem cells (iPSCs) offers a new strategy for modelling human disease. Recent studies have reported the derivation and differentiation of disease-specific human iPSCs. However, a key challenge in the field is the demonstration of disease-related phenotypes and the ability to model pathogenesis and treatment of disease in iPSCs. Familial dysautonomia (FD) is a rare but fatal peripheral neuropathy, caused by a point mutation in the IKBKAP gene involved in transcriptional elongation. The disease is characterized by the depletion of autonomic and sensory neurons. The specificity to the peripheral nervous system and the mechanism of neuron loss in FD are poorly understood owing to the lack of an appropriate model system. Here we report the derivation of patient-specific FD-iPSCs and the directed differentiation into cells of all three germ layers including peripheral neurons. Gene expression analysis in purified FD-iPSC-derived lineages demonstrates tissue-specific mis-splicing of IKBKAP in vitro. Patient-specific neural crest precursors express particularly low levels of normal IKBKAP transcript, suggesting a mechanism for disease specificity. FD pathogenesis is further characterized by transcriptome analysis and cell-based assays revealing marked defects in neurogenic differentiation and migration behaviour. Furthermore, we use FD-iPSCs for validating the potency of candidate drugs in reversing aberrant splicing and ameliorating neuronal differentiation and migration. Our study illustrates the promise of iPSC technology for gaining new insights into human disease pathogenesis and treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784695/" 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/PMC2784695/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Gabsang -- Papapetrou, Eirini P -- Kim, Hyesoo -- Chambers, Stuart M -- Tomishima, Mark J -- Fasano, Christopher A -- Ganat, Yosif M -- Menon, Jayanthi -- Shimizu, Fumiko -- Viale, Agnes -- Tabar, Viviane -- Sadelain, Michel -- Studer, Lorenz -- R01 NS052671/NS/NINDS NIH HHS/ -- R01 NS052671-03/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):402-6. doi: 10.1038/nature08320. Epub 2009 Aug 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693009" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Alternative Splicing/drug effects/genetics ; Animals ; Carrier Proteins/genetics ; Cell Dedifferentiation ; Cell Differentiation ; Cell Lineage ; Cell Movement ; Cells, Cultured ; Child ; Dysautonomia, Familial/drug therapy/genetics/*pathology/*therapy ; Female ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling ; Humans ; Kinetin/pharmacology/therapeutic use ; Male ; Mice ; *Models, Biological ; Neural Crest/cytology/drug effects ; Organ Specificity ; Phenotype ; Pluripotent Stem Cells/cytology/drug effects/*metabolism/*transplantation
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  • 73
    Publication Date: 2009-01-09
    Description: Haematopoietic stem cells (HSCs) are the founder cells of the adult haematopoietic system, and thus knowledge of the molecular program directing their generation during development is important for regenerative haematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus-the aorta, vitelline and umbilical arteries, yolk sac and placenta. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters and that Runx1 functions during the transition from 'haemogenic endothelium' to HSCs. Here we show by conditional deletion that Runx1 activity in vascular-endothelial-cadherin-positive endothelial cells is indeed essential for intra-arterial cluster, haematopoietic progenitor and HSC formation in mice. In contrast, Runx1 is not required in cells expressing Vav1, one of the first pan-haematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for haematopoietic progenitor and HSC formation from the vasculature, but its requirement ends once or before Vav is expressed.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744041/" 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/PMC2744041/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Michael J -- Yokomizo, Tomomasa -- Zeigler, Brandon M -- Dzierzak, Elaine -- Speck, Nancy A -- CA23108/CA/NCI NIH HHS/ -- R01 CA058343/CA/NCI NIH HHS/ -- R01DK54077/DK/NIDDK NIH HHS/ -- R01HL091724/HL/NHLBI NIH HHS/ -- R37 DK054077/DK/NIDDK NIH HHS/ -- R37 DK054077-09/DK/NIDDK NIH HHS/ -- T32 AI-07519/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):887-91. doi: 10.1038/nature07619. Epub 2009 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19129762" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Cadherins/metabolism ; *Cell Differentiation ; Core Binding Factor Alpha 2 Subunit/genetics/*metabolism ; Endothelial Cells/*cytology ; Female ; *Gene Expression Regulation, Developmental ; Hematopoietic Stem Cells/*cytology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Proto-Oncogene Proteins c-vav/metabolism
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  • 74
    Publication Date: 2009-05-05
    Description: Culture is typically viewed as consisting of traits inherited epigenetically, through social learning. However, cultural diversity has species-typical constraints, presumably of genetic origin. A celebrated, if contentious, example is whether a universal grammar constrains syntactic diversity in human languages. Oscine songbirds exhibit song learning and provide biologically tractable models of culture: members of a species show individual variation in song and geographically separated groups have local song dialects. Different species exhibit distinct song cultures, suggestive of genetic constraints. Without such constraints, innovations and copying errors should cause unbounded variation over multiple generations or geographical distance, contrary to observations. Here we report an experiment designed to determine whether wild-type song culture might emerge over multiple generations in an isolated colony founded by isolates, and, if so, how this might happen and what type of social environment is required. Zebra finch isolates, unexposed to singing males during development, produce song with characteristics that differ from the wild-type song found in laboratory or natural colonies. In tutoring lineages starting from isolate founders, we quantified alterations in song across tutoring generations in two social environments: tutor-pupil pairs in sound-isolated chambers and an isolated semi-natural colony. In both settings, juveniles imitated the isolate tutors but changed certain characteristics of the songs. These alterations accumulated over learning generations. Consequently, songs evolved towards the wild-type in three to four generations. Thus, species-typical song culture can appear de novo. Our study has parallels with language change and evolution. In analogy to models in quantitative genetics, we model song culture as a multigenerational phenotype partly encoded genetically in an isolate founding population, influenced by environmental variables and taking multiple generations to emerge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693086/" 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/PMC2693086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feher, Olga -- Wang, Haibin -- Saar, Sigal -- Mitra, Partha P -- Tchernichovski, Ofer -- R01 DC004722/DC/NIDCD NIH HHS/ -- R01 DC004722-09/DC/NIDCD NIH HHS/ -- England -- Nature. 2009 May 28;459(7246):564-8. doi: 10.1038/nature07994. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, City College, City University of New York, New York 10031, USA. olcifeher@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412161" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Culture ; Female ; Finches/*physiology ; Instinct ; Learning/physiology ; Male ; *Models, Biological ; Social Isolation ; Vocalization, Animal/*physiology
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  • 75
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    Nature Publishing Group (NPG)
    Publication Date: 2009-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feil, Robert -- England -- Nature. 2009 Sep 17;461(7262):359-60. doi: 10.1038/461359a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759613" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *DNA Methylation ; Embryo, Mammalian/cytology/embryology/metabolism ; Female ; *Genomic Imprinting ; Histones/*metabolism ; Humans ; Male ; Mice ; Oocytes/metabolism ; Oxidoreductases, N-Demethylating/*metabolism
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  • 76
    Publication Date: 2009-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nosengo, Nicola -- England -- Nature. 2009 Dec 3;462(7273):560-1. doi: 10.1038/462560a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956234" target="_blank"〉PubMed〈/a〉
    Keywords: *Acoustics ; Animal Communication ; Animals ; Female ; Male ; Mediterranean Sea ; Seasons ; *Seawater ; Whales/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 77
    Publication Date: 2009-09-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vasquez, Valeria -- Perozo, Eduardo -- England -- Nature. 2009 Sep 3;461(7260):47-9. doi: 10.1038/461047a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19727188" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; Ion Channel Gating/*physiology ; Ion Channels/*chemistry/*metabolism ; Models, Biological ; Models, Molecular ; Mycobacterium tuberculosis/chemistry ; Pressure ; Protein Structure, Quaternary ; Staphylococcus aureus/*chemistry
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  • 78
    Publication Date: 2009-07-25
    Description: Spatially synchronized fluctuations in system state are common in physical and biological systems ranging from individual atoms to species as diverse as viruses, insects and mammals. Although the causal factors are well known for many synchronized phenomena, several processes concurrently have an impact on spatial synchrony of species, making their separate effects and interactions difficult to quantify. Here we develop a general stochastic model of predator-prey spatial dynamics to predict the outcome of a laboratory microcosm experiment testing for interactions among all known synchronizing factors: (1) dispersal of individuals between populations; (2) spatially synchronous fluctuations in exogenous environmental factors (the Moran effect); and (3) interactions with other species (for example, predators) that are themselves spatially synchronized. The Moran effect synchronized populations of the ciliate protist Tetrahymena pyriformis; however, dispersal only synchronized prey populations in the presence of the predator Euplotes patella. Both model and data indicate that synchrony depends on cyclic dynamics generated by the predator. Dispersal, but not the Moran effect, 'phase-locks' cycles, which otherwise become 'decoherent' and drift out of phase. In the absence of cycles, phase-locking is not possible and the synchronizing effect of dispersal is negligible. Interspecific interactions determine population synchrony, not by providing an additional source of synchronized fluctuations, but by altering population dynamics and thereby enhancing the action of dispersal. Our results are robust to wide variation in model parameters representative of many natural predator-prey or host-pathogen systems. This explains why cyclic systems provide many of the most dramatic examples of spatial synchrony in nature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vasseur, David A -- Fox, Jeremy W -- England -- Nature. 2009 Aug 20;460(7258):1007-10. doi: 10.1038/nature08208. Epub 2009 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06520, USA. david.vasseur@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626006" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Euplotes/*physiology ; *Food Chain ; Models, Biological ; Population Dynamics ; Predatory Behavior/*physiology ; Stochastic Processes ; Tetrahymena pyriformis/*physiology
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  • 79
    Publication Date: 2009-07-07
    Description: Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains. Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity. Here we show that Batf is required for the differentiation of IL17-producing T helper (T(H)17) cells. T(H)17 cells comprise a CD4(+) T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity. Batf(-/-) mice have normal T(H)1 and T(H)2 differentiation, but show a defect in T(H)17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf(-/-) T cells fail to induce known factors required for T(H)17 differentiation, such as RORgamma t (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of IL21 nor the overexpression of RORgamma t fully restores IL17 production in Batf(-/-) T cells. The Il17 promoter is BATF-responsive, and after T(H)17 differentiation, BATF binds conserved intergenic elements in the Il17a-Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in T(H)17 differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716014/" 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/PMC2716014/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schraml, Barbara U -- Hildner, Kai -- Ise, Wataru -- Lee, Wan-Ling -- Smith, Whitney A-E -- Solomon, Ben -- Sahota, Gurmukh -- Sim, Julia -- Mukasa, Ryuta -- Cemerski, Saso -- Hatton, Robin D -- Stormo, Gary D -- Weaver, Casey T -- Russell, John H -- Murphy, Theresa L -- Murphy, Kenneth M -- AI035783/AI/NIAID NIH HHS/ -- AR049293/AR/NIAMS NIH HHS/ -- GM07200/GM/NIGMS NIH HHS/ -- HG00249/HG/NHGRI NIH HHS/ -- R01 HG000249/HG/NHGRI NIH HHS/ -- R01 HG000249-20/HG/NHGRI NIH HHS/ -- T32 GM008802/GM/NIGMS NIH HHS/ -- T32 GM008802-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 16;460(7253):405-9. doi: 10.1038/nature08114. Epub 2009 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19578362" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic-Leucine Zipper Transcription Factors/deficiency/genetics/*metabolism ; *Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/genetics ; Female ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Interleukin-17/biosynthesis/genetics/*metabolism ; Interleukins/genetics/metabolism/pharmacology ; Lymph Nodes/metabolism ; Male ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Promoter Regions, Genetic/genetics ; Receptors, Retinoic Acid/genetics/metabolism ; Receptors, Thyroid Hormone/genetics/metabolism ; T-Lymphocytes, Helper-Inducer/*cytology/*metabolism ; Transcription Factor AP-1/deficiency/genetics/*metabolism
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  • 80
    Publication Date: 2009-12-18
    Description: In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter and progress through S phase. Using a panel of tissue-specific cre-transgenic mice and conditional E2f alleles we examined the effects of E2f1, E2f2 and E2f3 triple deficiency in murine embryonic stem cells, embryos and small intestines. We show that in normal dividing progenitor cells E2f1-3 function as transcriptional activators, but contrary to the current view, are dispensable for cell division and instead are necessary for cell survival. In differentiating cells E2f1-3 function in a complex with Rb as repressors to silence E2f targets and facilitate exit from the cell cycle. The inactivation of Rb in differentiating cells resulted in a switch of E2f1-3 from repressors to activators, leading to the superactivation of E2f responsive targets and ectopic cell divisions. Loss of E2f1-3 completely suppressed these phenotypes caused by Rb deficiency. This work contextualizes the activator versus repressor functions of E2f1-3 in vivo, revealing distinct roles in dividing versus differentiating cells and in normal versus cancer-like cell cycles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806193/" 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/PMC2806193/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chong, Jean-Leon -- Wenzel, Pamela L -- Saenz-Robles, M Teresa -- Nair, Vivek -- Ferrey, Antoney -- Hagan, John P -- Gomez, Yorman M -- Sharma, Nidhi -- Chen, Hui-Zi -- Ouseph, Madhu -- Wang, Shu-Huei -- Trikha, Prashant -- Culp, Brian -- Mezache, Louise -- Winton, Douglas J -- Sansom, Owen J -- Chen, Danian -- Bremner, Rod -- Cantalupo, Paul G -- Robinson, Michael L -- Pipas, James M -- Leone, Gustavo -- 5 T32 CA106196-04/CA/NCI NIH HHS/ -- CA098956/CA/NCI NIH HHS/ -- P01CA097189/CA/NCI NIH HHS/ -- R01 CA098956/CA/NCI NIH HHS/ -- R01 CA098956-06A2/CA/NCI NIH HHS/ -- R01CA82259/CA/NCI NIH HHS/ -- R01CA85619/CA/NCI NIH HHS/ -- R01HD04470/HD/NICHD NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):930-4. doi: 10.1038/nature08677.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016602" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Apoptosis ; Cell Cycle/genetics/physiology ; *Cell Differentiation ; Cell Proliferation ; E2F Transcription Factors/deficiency/genetics/*metabolism ; E2F1 Transcription Factor/deficiency/genetics/metabolism ; E2F2 Transcription Factor/deficiency/genetics/metabolism ; E2F3 Transcription Factor/deficiency/genetics/metabolism ; Embryo, Mammalian/cytology/metabolism ; Embryonic Stem Cells/*cytology/*metabolism ; Female ; *Gene Expression Regulation ; Intestine, Small/cytology/metabolism ; Mice ; Mice, Transgenic ; Repressor Proteins/deficiency/genetics/*metabolism ; Retinoblastoma Protein/deficiency/metabolism
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  • 81
    Publication Date: 2009-02-24
    Description: Several independent, genome-wide association studies have identified a strong correlation between body mass index and polymorphisms in the human FTO gene. Common variants in the first intron define a risk allele predisposing to obesity, with homozygotes for the risk allele weighing approximately 3 kilograms more than homozygotes for the low risk allele. Nevertheless, the functional role of FTO in energy homeostasis remains elusive. Here we show that the loss of Fto in mice leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass. The leanness of Fto-deficient mice develops as a consequence of increased energy expenditure and systemic sympathetic activation, despite decreased spontaneous locomotor activity and relative hyperphagia. Taken together, these experiments provide, to our knowledge, the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Julia -- Koch, Linda -- Emmerling, Christian -- Vierkotten, Jeanette -- Peters, Thomas -- Bruning, Jens C -- Ruther, Ulrich -- England -- Nature. 2009 Apr 16;458(7240):894-8. doi: 10.1038/nature07848. Epub 2009 Feb 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, Universitatsstr. 1, D-40225 Dusseldorf, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19234441" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism ; Adiposity/genetics ; Animals ; Animals, Newborn ; Body Weight/genetics ; Brain/metabolism ; Eating/physiology ; Embryo, Mammalian/anatomy & histology/embryology ; Energy Metabolism/genetics/physiology ; Female ; Growth Disorders/genetics/physiopathology ; Homozygote ; Hyperphagia/genetics ; Insulin/metabolism ; Male ; Mice ; Mixed Function Oxygenases ; Motor Activity/genetics/physiology ; Obesity/*genetics/prevention & control ; Oxo-Acid-Lyases/*deficiency/genetics/*metabolism ; Phenotype ; Sympathetic Nervous System/physiology ; Thinness/*genetics
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  • 82
    Publication Date: 2009-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fitch, W Tecumseh -- England -- Nature. 2009 May 28;459(7246):519-20. doi: 10.1038/459519a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child ; *Culture ; Female ; Finches/*physiology ; Humans ; Instinct ; *Language ; Learning/physiology ; Linguistics ; Male ; *Models, Biological ; Social Isolation ; Vocalization, Animal/*physiology
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  • 83
    Publication Date: 2009-06-12
    Description: Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture. One such compound, phosphinothricin tripeptide, contains the unusual amino acid phosphinothricin attached to two alanine residues. Synthetic phosphinothricin (glufosinate) is a component of two top-selling herbicides (Basta and Liberty), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during phosphinothricin tripeptide biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP). Here we report the in vitro reconstitution of this unprecedented C(sp(3))-C(sp(3)) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-haem iron(ii)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalysed by the 2-His-1-carboxylate mononuclear non-haem iron family of enzymes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874955/" 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/PMC2874955/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cicchillo, Robert M -- Zhang, Houjin -- Blodgett, Joshua A V -- Whitteck, John T -- Li, Gongyong -- Nair, Satish K -- van der Donk, Wilfred A -- Metcalf, William W -- P01 GM077596/GM/NIGMS NIH HHS/ -- P01 GM077596-03/GM/NIGMS NIH HHS/ -- R01 GM059334/GM/NIGMS NIH HHS/ -- R01 GM059334-09/GM/NIGMS NIH HHS/ -- R01 GM59334/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jun 11;459(7248):871-4. doi: 10.1038/nature07972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19516340" target="_blank"〉PubMed〈/a〉
    Keywords: Aminobutyrates/*chemistry/*metabolism ; Biocatalysis ; Crystallography, X-Ray ; Dioxygenases/chemistry/genetics/*metabolism ; Escherichia coli ; Formates/metabolism ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Models, Biological ; Models, Molecular ; Molecular Conformation ; Organophosphonates/metabolism
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  • 84
    Publication Date: 2009-08-14
    Description: Ecological communities characteristically contain a wide diversity of species with important functional, economic and aesthetic value. Ecologists have long questioned how this diversity is maintained. Classic theory shows that stable coexistence requires competitors to differ in their niches; this has motivated numerous investigations of ecological differences presumed to maintain diversity. That niche differences are key to coexistence, however, has recently been challenged by the neutral theory of biodiversity, which explains coexistence with the equivalence of competitors. The ensuing controversy has motivated calls for a better understanding of the collective importance of niche differences for the diversity observed in ecological communities. Here we integrate theory and experimentation to show that niche differences collectively stabilize the dynamics of experimental communities of serpentine annual plants. We used field-parameterized population models to develop a null expectation for community dynamics without the stabilizing effects of niche differences. The population growth rates predicted by this null model varied by several orders of magnitude between species, which is sufficient for rapid competitive exclusion. Moreover, after two generations of community change in the field, Shannon diversity was over 50 per cent greater in communities stabilized by niche differences relative to those exhibiting dynamics predicted by the null model. Finally, in an experiment manipulating species' relative abundances, population growth rates increased when species became rare--the demographic signature of niche differences. Our work thus provides strong evidence that species differences have a critical role in stabilizing species diversity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levine, Jonathan M -- HilleRisLambers, Janneke -- England -- Nature. 2009 Sep 10;461(7261):254-7. doi: 10.1038/nature08251. Epub 2009 Aug 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, California 93106, USA. levine@lifesci.ucsb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19675568" target="_blank"〉PubMed〈/a〉
    Keywords: *Biodiversity ; California ; *Ecosystem ; Models, Biological ; Plant Development ; *Plant Physiological Phenomena ; Plants/classification ; Population Dynamics ; Seeds/physiology
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  • 85
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Monya -- England -- Nature. 2009 Apr 23;458(7241):962-5. doi: 10.1038/458962a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396119" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*trends ; Cellular Reprogramming/drug effects/*genetics/*physiology ; Competitive Behavior ; Drug Evaluation, Preclinical/methods/trends ; Embryonic Stem Cells/cytology/metabolism ; Female ; Humans ; Mice ; Pluripotent Stem Cells/*cytology/drug effects/*metabolism/pathology ; Safety ; Teratoma/pathology
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  • 86
    Publication Date: 2009-09-04
    Description: Differential DNA methylation of the paternal and maternal alleles regulates the parental origin-specific expression of imprinted genes in mammals. The methylation imprints are established in male and female germ cells during gametogenesis, and the de novo DNA methyltransferase DNMT3A and its cofactor DNMT3L are required in this process. However, the mechanisms underlying locus- and parental-specific targeting of the de novo DNA methylation machinery in germline imprinting are poorly understood. Here we show that amine oxidase (flavin-containing) domain 1 (AOF1), a protein related to the lysine demethylase KDM1 (also known as LSD1), functions as a histone H3 lysine 4 (H3K4) demethylase and is required for de novo DNA methylation of some imprinted genes in oocytes. AOF1, now renamed lysine demethylase 1B (KDM1B) following a new nomenclature, is highly expressed in growing oocytes where genomic imprints are established. Targeted disruption of the gene encoding KDM1B had no effect on mouse development and oogenesis. However, oocytes from KDM1B-deficient females showed a substantial increase in H3K4 methylation and failed to set up the DNA methylation marks at four out of seven imprinted genes examined. Embryos derived from these oocytes showed biallelic expression or biallelic suppression of the affected genes and died before mid-gestation. Our results suggest that demethylation of H3K4 is critical for establishing the DNA methylation imprints during oogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciccone, David N -- Su, Hui -- Hevi, Sarah -- Gay, Frederique -- Lei, Hong -- Bajko, Jeffrey -- Xu, Guoliang -- Li, En -- Chen, Taiping -- England -- Nature. 2009 Sep 17;461(7262):415-8. doi: 10.1038/nature08315. Epub 2009 Sep 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Epigenetics Program, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19727073" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *DNA Methylation ; Embryo Loss/genetics ; Embryo, Mammalian/metabolism ; Female ; Gene Expression Regulation, Developmental ; Genes, Developmental/genetics ; *Genomic Imprinting ; Histones/*metabolism ; Male ; Mice ; *Mothers ; NIH 3T3 Cells ; Oocytes/metabolism ; Oxidoreductases, N-Demethylating/deficiency/genetics/*metabolism
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  • 87
    Publication Date: 2009-09-18
    Description: Adaptive radiations often follow the evolution of key traits, such as the origin of the amniotic egg and the subsequent radiation of terrestrial vertebrates. The mechanism by which a species determines the sex of its offspring has been linked to critical ecological and life-history traits but not to major adaptive radiations, in part because sex-determining mechanisms do not fossilize. Here we establish a previously unknown coevolutionary relationship in 94 amniote species between sex-determining mechanism and whether a species bears live young or lays eggs. We use that relationship to predict the sex-determining mechanism in three independent lineages of extinct Mesozoic marine reptiles (mosasaurs, sauropterygians and ichthyosaurs), each of which is known from fossils to have evolved live birth. Our results indicate that each lineage evolved genotypic sex determination before acquiring live birth. This enabled their pelagic radiations, where the relatively stable temperatures of the open ocean constrain temperature-dependent sex determination in amniote species. Freed from the need to move and nest on land, extreme physical adaptations to a pelagic lifestyle evolved in each group, such as the fluked tails, dorsal fins and wing-shaped limbs of ichthyosaurs. With the inclusion of ichthyosaurs, mosasaurs and sauropterygians, genotypic sex determination is present in all known fully pelagic amniote groups (sea snakes, sirenians and cetaceans), suggesting that this mode of sex determination and the subsequent evolution of live birth are key traits required for marine adaptive radiations in amniote lineages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Organ, Chris L -- Janes, Daniel E -- Meade, Andrew -- Pagel, Mark -- 1 F32 GM075490-01/GM/NIGMS NIH HHS/ -- 5 F32 GM072494/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):389-92. doi: 10.1038/nature08350.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Museum of Comparative Zoology, Harvard University, 26 Oxford Street, Cambridge, Massachusetts 02138, USA. corgan@oeb.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759619" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics/physiology ; Algorithms ; Animals ; Bayes Theorem ; *Biological Evolution ; *Extinction, Biological ; Female ; Fossils ; Genotype ; History, Ancient ; Male ; Marine Biology ; Markov Chains ; Monte Carlo Method ; Oviposition/genetics/physiology ; Phylogeny ; Reptiles/classification/*genetics/*physiology ; Sex Chromosomes/*genetics ; *Sex Determination Processes ; Sex Ratio ; Temperature ; Viviparity, Nonmammalian/genetics/*physiology
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  • 88
    Publication Date: 2009-02-20
    Description: The response of terrestrial vegetation to a globally changing environment is central to predictions of future levels of atmospheric carbon dioxide. The role of tropical forests is critical because they are carbon-dense and highly productive. Inventory plots across Amazonia show that old-growth forests have increased in carbon storage over recent decades, but the response of one-third of the world's tropical forests in Africa is largely unknown owing to an absence of spatially extensive observation networks. Here we report data from a ten-country network of long-term monitoring plots in African tropical forests. We find that across 79 plots (163 ha) above-ground carbon storage in live trees increased by 0.63 Mg C ha(-1) yr(-1) between 1968 and 2007 (95% confidence interval (CI), 0.22-0.94; mean interval, 1987-96). Extrapolation to unmeasured forest components (live roots, small trees, necromass) and scaling to the continent implies a total increase in carbon storage in African tropical forest trees of 0.34 Pg C yr(-1) (CI, 0.15-0.43). These reported changes in carbon storage are similar to those reported for Amazonian forests per unit area, providing evidence that increasing carbon storage in old-growth forests is a pan-tropical phenomenon. Indeed, combining all standardized inventory data from this study and from tropical America and Asia together yields a comparable figure of 0.49 Mg C ha(-1) yr(-1) (n = 156; 562 ha; CI, 0.29-0.66; mean interval, 1987-97). This indicates a carbon sink of 1.3 Pg C yr(-1) (CI, 0.8-1.6) across all tropical forests during recent decades. Taxon-specific analyses of African inventory and other data suggest that widespread changes in resource availability, such as increasing atmospheric carbon dioxide concentrations, may be the cause of the increase in carbon stocks, as some theory and models predict.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, Simon L -- Lopez-Gonzalez, Gabriela -- Sonke, Bonaventure -- Affum-Baffoe, Kofi -- Baker, Timothy R -- Ojo, Lucas O -- Phillips, Oliver L -- Reitsma, Jan M -- White, Lee -- Comiskey, James A -- Djuikouo K, Marie-Noel -- Ewango, Corneille E N -- Feldpausch, Ted R -- Hamilton, Alan C -- Gloor, Manuel -- Hart, Terese -- Hladik, Annette -- Lloyd, Jon -- Lovett, Jon C -- Makana, Jean-Remy -- Malhi, Yadvinder -- Mbago, Frank M -- Ndangalasi, Henry J -- Peacock, Julie -- Peh, Kelvin S-H -- Sheil, Douglas -- Sunderland, Terry -- Swaine, Michael D -- Taplin, James -- Taylor, David -- Thomas, Sean C -- Votere, Raymond -- Woll, Hannsjorg -- England -- Nature. 2009 Feb 19;457(7232):1003-6. doi: 10.1038/nature07771.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Earth and Biosphere Institute, School of Geography, University of Leeds, Leeds LS2 9JT, UK. s.l.lewis@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19225523" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Atmosphere/chemistry ; Biomass ; Carbon/analysis/*metabolism ; Carbon Dioxide/analysis/metabolism ; Models, Biological ; Trees/anatomy & histology/chemistry/growth & development/*metabolism ; *Tropical Climate ; Wilderness ; Wood/analysis/chemistry
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  • 89
    Publication Date: 2009-06-26
    Description: Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification. Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to the trans-Golgi network and interacts with components of the retromer complex, which in yeast has been linked to target of rapamycin (TOR) signalling. Mechanistically, GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo. Thus, genomic and genetic, biological, functional and biochemical data in yeast and humans establishes GOLPH3 as a new oncogene that is commonly targeted for amplification in human cancer, and is capable of modulating the response to rapamycin, a cancer drug in clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753613/" 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/PMC2753613/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, Kenneth L -- Kabbarah, Omar -- Liang, Mei-Chih -- Ivanova, Elena -- Anagnostou, Valsamo -- Wu, Joyce -- Dhakal, Sabin -- Wu, Min -- Chen, Shujuan -- Feinberg, Tamar -- Huang, Joseph -- Saci, Abdel -- Widlund, Hans R -- Fisher, David E -- Xiao, Yonghong -- Rimm, David L -- Protopopov, Alexei -- Wong, Kwok-Kin -- Chin, Lynda -- 5-T32-AR07098-31/AR/NIAMS NIH HHS/ -- P50 CA090578/CA/NCI NIH HHS/ -- P50 CA093683/CA/NCI NIH HHS/ -- P50 CA093683-06A20011/CA/NCI NIH HHS/ -- P50 CA93683/CA/NCI NIH HHS/ -- R0-1 CA 114277/CA/NCI NIH HHS/ -- R01 AG2400401/AG/NIA NIH HHS/ -- R01 CA093947/CA/NCI NIH HHS/ -- R01 CA093947-08/CA/NCI NIH HHS/ -- R01 CA114277/CA/NCI NIH HHS/ -- R01 CA114277-04/CA/NCI NIH HHS/ -- R01 CA122794/CA/NCI NIH HHS/ -- R01 CA122794-03/CA/NCI NIH HHS/ -- R01 CA93947/CA/NCI NIH HHS/ -- T32 AR007098/AR/NIAMS NIH HHS/ -- T32 AR007098-32/AR/NIAMS NIH HHS/ -- England -- Nature. 2009 Jun 25;459(7250):1085-90. doi: 10.1038/nature08109.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibiotics, Antineoplastic/*pharmacology ; Cell Line, Tumor/drug effects ; DNA-Binding Proteins/genetics ; Female ; Gene Knockdown Techniques ; Humans ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; Neoplasms/*physiopathology ; Protein Kinases/genetics/*metabolism ; Saccharomyces cerevisiae/genetics ; *Signal Transduction ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases ; Transcription Factors/genetics
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  • 90
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clark, Andrew J -- Summers, Adam P -- England -- Nature. 2009 Jun 18;459(7249):919-20. doi: 10.1038/459919a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536249" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomechanical Phenomena ; Body Weight ; Friction ; Gait/physiology ; Locomotion/*physiology ; Models, Biological ; Snakes/*physiology
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  • 91
    Publication Date: 2009-03-06
    Description: Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3alpha (also known as CCL20), plasmacytoid dendritic cells and CCR5(+ )cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4(+) T cells to fuel this obligate expansion. We then show that glycerol monolaurate-a widely used antimicrobial compound with inhibitory activity against the production of MIP-3alpha and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785041/" 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/PMC2785041/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Qingsheng -- Estes, Jacob D -- Schlievert, Patrick M -- Duan, Lijie -- Brosnahan, Amanda J -- Southern, Peter J -- Reilly, Cavan S -- Peterson, Marnie L -- Schultz-Darken, Nancy -- Brunner, Kevin G -- Nephew, Karla R -- Pambuccian, Stefan -- Lifson, Jeffrey D -- Carlis, John V -- Haase, Ashley T -- G20 RR022780/RR/NCRR NIH HHS/ -- G20 RR022780-01A1/RR/NCRR NIH HHS/ -- HHSN266200400088C/PHS HHS/ -- N01-CO-12400/CO/NCI NIH HHS/ -- P01 AI066314/AI/NIAID NIH HHS/ -- P01 AI066314-040003/AI/NIAID NIH HHS/ -- P51 RR000167/RR/NCRR NIH HHS/ -- P51 RR000167-440109/RR/NCRR NIH HHS/ -- P51 RR000167-440189/RR/NCRR NIH HHS/ -- P51 RR000167-46S27592/RR/NCRR NIH HHS/ -- R21 AI071976/AI/NIAID NIH HHS/ -- R21 AI071976-02/AI/NIAID NIH HHS/ -- RR020141-01/RR/NCRR NIH HHS/ -- RR15459-01/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Apr 23;458(7241):1034-8. doi: 10.1038/nature07831. Epub 2009 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Medical School, University of Minnesota, MMC 196, 420 Delaware Street S.E., Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262509" target="_blank"〉PubMed〈/a〉
    Keywords: Acute Disease ; Animals ; Body Fluids/metabolism/virology ; CD4-Positive T-Lymphocytes/immunology/virology ; Cell Cycle Proteins/metabolism ; Cervix Uteri/drug effects/immunology/virology ; Chemokine CCL20/immunology/metabolism ; Dendritic Cells/immunology/metabolism ; Female ; GPI-Linked Proteins ; Gene Expression Profiling ; HIV-1/physiology ; Interleukin-8/metabolism ; Laurates/*pharmacology ; Macaca mulatta/*virology ; Membrane Proteins/metabolism ; Monoglycerides/*pharmacology ; Mucous Membrane/*drug effects/immunology/*virology ; RNA, Viral/blood ; Receptors, CCR5/immunology/metabolism ; Simian Acquired Immunodeficiency Syndrome/genetics/*prevention & ; control/*transmission/virology ; Simian Immunodeficiency Virus/drug effects/genetics/growth & ; development/physiology ; Time Factors ; Vagina/drug effects/virology
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  • 92
    Publication Date: 2009-11-17
    Description: Mechanical pain contributes to the morbidity associated with inflammation and trauma, but primary sensory neurons that convey the sensation of acute and persistent mechanical pain have not been identified. Dorsal root ganglion (DRG) neurons transmit sensory information to the spinal cord using the excitatory transmitter glutamate, a process that depends on glutamate transport into synaptic vesicles for regulated exocytotic release. Here we report that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8). In the dorsal horn of the spinal cord, these afferents project to lamina I and the innermost layer of lamina II, which has previously been implicated in persistent pain caused by injury. Because the different VGLUT isoforms generally have a non-redundant pattern of expression, we used Vglut3 knockout mice to assess the role of VGLUT3(+) primary afferents in the behavioural response to somatosensory input. The loss of VGLUT3 specifically impairs mechanical pain sensation, and in particular the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma. Direct recording from VGLUT3(+) neurons in the DRG further identifies them as a poorly understood population of unmyelinated, low threshold mechanoreceptors (C-LTMRs). The analysis of Vglut3(-/-) mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810205/" 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/PMC2810205/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seal, Rebecca P -- Wang, Xidao -- Guan, Yun -- Raja, Srinivasa N -- Woodbury, C Jeffery -- Basbaum, Allan I -- Edwards, Robert H -- F32 MH068085/MH/NIMH NIH HHS/ -- F32 MH068085-02/MH/NIMH NIH HHS/ -- R01 MH050712/MH/NIMH NIH HHS/ -- R01 MH050712-17/MH/NIMH NIH HHS/ -- R01 NS044094/NS/NINDS NIH HHS/ -- R01 NS044094-06/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Dec 3;462(7273):651-5. doi: 10.1038/nature08505. Epub 2009 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco School of Medicine, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19915548" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Transport Systems, Acidic/genetics/*metabolism ; Animals ; Behavior, Animal/physiology ; Female ; Ganglia, Spinal/*metabolism ; Gene Expression Regulation ; Hypersensitivity/*genetics/*physiopathology ; Mechanoreceptors/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pain/*genetics ; Wounds and Injuries/*physiopathology
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  • 93
    Publication Date: 2009-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clayton, Nicky -- England -- Nature. 2009 Nov 19;462(7271):288. doi: 10.1038/462288a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924197" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Birds/*physiology ; *Dancing/physiology/psychology ; Female ; Humans ; Male ; Music/psychology
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  • 94
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    Nature Publishing Group (NPG)
    Publication Date: 2009-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seastedt, Tim -- England -- Nature. 2009 Jun 11;459(7248):783-4. doi: 10.1038/459783a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19516327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; Europe ; Models, Biological ; *Plant Development ; Plants/*microbiology ; Population Growth ; United States
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  • 95
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-05-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seehausen, Ole -- England -- Nature. 2009 Apr 30;458(7242):1122-3. doi: 10.1038/4581122a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407790" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; *Biological Evolution ; British Columbia ; *Ecosystem ; Fishes/*classification/*physiology ; Food Chain ; Fresh Water ; Genetic Speciation ; Models, Biological
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  • 96
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2009 Nov 26;462(7272):406-7. doi: 10.1038/462406a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940894" target="_blank"〉PubMed〈/a〉
    Keywords: Consumer Product Safety/standards ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Levonorgestrel/standards ; New York City ; United States ; United States Food and Drug Administration/economics/*organization & ; administration/*standards/trends
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  • 97
    Publication Date: 2009-04-28
    Description: Fruitflies show robust attraction to food odours, which usually excite several glomeruli. To understand how the representation of such odours leads to behaviour, we used genetic tools to dissect the contribution of each activated glomerulus. Apple cider vinegar triggers robust innate attraction at a relatively low concentration, which activates six glomeruli. By silencing individual glomeruli, here we show that the absence of activity in two glomeruli, DM1 and VA2, markedly reduces attraction. Conversely, when each of these two glomeruli was selectively activated, flies showed as robust an attraction to vinegar as wild-type flies. Notably, a higher concentration of vinegar excites an additional glomerulus and is less attractive to flies. We show that activation of the extra glomerulus is necessary and sufficient to mediate the behavioural switch. Together, these results indicate that individual glomeruli, rather than the entire pattern of active glomeruli, mediate innate behavioural output.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702439/" 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/PMC2702439/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Semmelhack, Julia L -- Wang, Jing W -- R01 DC009597/DC/NIDCD NIH HHS/ -- R01 DC009597-01/DC/NIDCD NIH HHS/ -- R01DC009597/DC/NIDCD NIH HHS/ -- England -- Nature. 2009 May 14;459(7244):218-23. doi: 10.1038/nature07983. Epub 2009 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396157" target="_blank"〉PubMed〈/a〉
    Keywords: Acetic Acid/*analysis/pharmacology ; Animals ; Animals, Genetically Modified ; Butyrates/pharmacology ; Calcium/analysis/metabolism ; Drosophila melanogaster/*anatomy & histology/drug effects/*physiology ; Feeding Behavior/drug effects/*physiology ; Female ; Fruit/chemistry ; Locomotion/drug effects/*physiology ; Malus/chemistry ; Odors/*analysis ; Smell/drug effects/*physiology
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  • 98
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2009 Nov 5;462(7269):20-1. doi: 10.1038/462020a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890297" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Biomedical Research/economics/*organization & administration ; Child ; *Environment ; Female ; Health Surveys ; Humans ; National Institutes of Health (U.S.)/economics/ethics/legislation & jurisprudence ; Placenta/pathology ; *Politics ; Pregnancy ; United States
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  • 99
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sendtner, Michael -- England -- Nature. 2009 Jan 15;457(7227):269-70. doi: 10.1038/457269a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148087" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation/drug effects ; Cell Separation ; *Cellular Reprogramming/drug effects ; Child ; Female ; Fibroblasts/cytology ; Humans ; Mice ; Models, Biological ; Motor Neurons/drug effects/metabolism/*pathology ; Muscular Atrophy, Spinal/drug therapy/metabolism/*pathology ; Pluripotent Stem Cells/cytology/drug effects/metabolism/*pathology ; Skin/*cytology ; Survival of Motor Neuron 1 Protein/genetics/metabolism
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  • 100
    Publication Date: 2009-08-12
    Description: Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. The suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a barrier not only in tumorigenicity, but also in iPS cell generation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917235/" 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/PMC2917235/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Hyenjong -- Takahashi, Kazutoshi -- Ichisaka, Tomoko -- Aoi, Takashi -- Kanagawa, Osami -- Nakagawa, Masato -- Okita, Keisuke -- Yamanaka, Shinya -- U01 HL100406/HL/NHLBI NIH HHS/ -- U01 HL100406-01/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1132-5. doi: 10.1038/nature08235. Epub 2009 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19668191" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Differentiation ; Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling ; Gene Silencing ; Genes, myc ; Humans ; Male ; Mice ; Oligonucleotide Array Sequence Analysis ; Plasmids/genetics ; Pluripotent Stem Cells/*cytology/*metabolism ; T-Lymphocytes/cytology ; Transfection ; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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