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  • Articles  (307)
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  • 2020-2024
  • 2010-2014  (307)
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  • 101
    Publication Date: 2010-03-20
    Description: Male pregnancy in seahorses, pipefishes and sea dragons (family Syngnathidae) represents a striking reproductive adaptation that has shaped the evolution of behaviour and morphology in this group of fishes. In many syngnathid species, males brood their offspring in a specialized pouch, which presumably evolved to facilitate male parental care. However, an unexplored possibility is that brood pouch evolution was partly shaped by parent-offspring or sexual conflict, processes that would result in trade-offs between current and future pregnancies. Here we report a controlled breeding experiment using the sexually dimorphic Gulf pipefish, Syngnathus scovelli, to test for post-copulatory sexual selection within broods and for trade-offs between successive male pregnancies as functions of female attractiveness. Offspring survivorship within a pregnancy was affected by the size of a male's mate, the number of eggs transferred and the male's sexual responsiveness. Significantly, we also found that embryo survivorship in a current pregnancy was negatively related to survivorship in the prior pregnancy, clearly demonstrating fitness trade-offs between broods. Overall, our data indicate that post-copulatory sexual selection and sexual conflict occur in Gulf pipefishes. The conflict seems to be mediated by a strategy of cryptic choice in which males increase rates of offspring abortion in pregnancies from unattractive mothers to retain resources for future reproductive opportunities. Hence, the male brood pouch of syngnathid fishes, which nurtures offspring, also seems to have an important role as an arbiter of conflict between the sexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paczolt, Kimberly A -- Jones, Adam G -- England -- Nature. 2010 Mar 18;464(7287):401-4. doi: 10.1038/nature08861.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, 3258 TAMU, Texas A&M University, College Station, Texas 77845, USA. kpaczolt@mail.bio.tamu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237568" target="_blank"〉PubMed〈/a〉
    Keywords: Abortion, Eugenic/veterinary ; Animals ; *Biological Evolution ; Body Size/physiology ; *Conflict (Psychology) ; *Copulation ; Embryo, Nonmammalian/embryology/physiology ; Embryonic Development/*physiology ; Female ; Male ; Mating Preference, Animal/*physiology ; Paternal Behavior ; Selection, Genetic ; *Sex ; Sex Characteristics ; Smegmamorpha/anatomy & histology/embryology/*physiology ; Survival Rate ; Texas
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 102
    Publication Date: 2010-08-21
    Description: The thymus develops from the third pharyngeal pouch of the anterior gut and provides the necessary environment for thymopoiesis (the process by which thymocytes differentiate into mature T lymphocytes) and the establishment and maintenance of self-tolerance. It contains thymic epithelial cells (TECs) that form a complex three-dimensional network organized in cortical and medullary compartments, the organization of which is notably different from simple or stratified epithelia. TECs have an essential role in the generation of self-tolerant thymocytes through expression of the autoimmune regulator Aire, but the mechanisms involved in the specification and maintenance of TECs remain unclear. Despite the different embryological origins of thymus and skin (endodermal and ectodermal, respectively), some cells of the thymic medulla express stratified-epithelium markers, interpreted as promiscuous gene expression. Here we show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured while conserving the capacity to integrate in a thymic epithelial network and to express major histocompatibility complex class II (MHC II) molecules and Aire. These cells can irreversibly adopt the fate of hair follicle multipotent stem cells when exposed to an inductive skin microenvironment; this change in fate is correlated with robust changes in gene expression. Hence, microenvironmental cues are sufficient here to re-direct epithelial cell fate, allowing crossing of primitive germ layer boundaries and an increase in potency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonfanti, Paola -- Claudinot, Stephanie -- Amici, Alessandro W -- Farley, Alison -- Blackburn, C Clare -- Barrandon, Yann -- England -- Nature. 2010 Aug 19;466(7309):978-82. doi: 10.1038/nature09269.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Stem Cell Dynamics, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20725041" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; *Cell Dedifferentiation ; Cell Lineage/physiology ; *Cell Transdifferentiation ; Cells, Cultured ; *Cellular Reprogramming ; Clone Cells/cytology/metabolism ; Epithelial Cells/*cytology/metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Hair Follicle/cytology ; Histocompatibility Antigens Class II/metabolism ; Male ; Mice ; Multipotent Stem Cells/*cytology/metabolism ; Rats ; Rats, Sprague-Dawley ; Skin/*cytology/embryology ; Thymus Gland/*cytology/embryology ; Transcription Factors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 103
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    Nature Publishing Group (NPG)
    Publication Date: 2010-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wadman, Meredith -- England -- Nature. 2010 May 13;465(7295):150-5. doi: 10.1038/465150a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463714" target="_blank"〉PubMed〈/a〉
    Keywords: Alabama ; Biotechnology/economics/organization & administration ; Education, Graduate/organization & administration ; Faculty/*organization & administration ; Female ; Homicide/*psychology ; Humans ; Male ; Research Personnel/*education/*psychology ; Universities/*manpower
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 104
    Publication Date: 2010-10-15
    Description: Meiotic crossover (CO) recombination establishes physical linkages between homologous chromosomes that are required for their proper segregation into developing gametes, and promotes genetic diversity by shuffling genetic material between parental chromosomes. COs require the formation of double strand breaks (DSBs) to create the substrate for strand exchange. DSBs occur in small intervals called hotspots and significant variation in hotspot usage exists between and among individuals. This variation is thought to reflect differences in sequence identity and chromatin structure, DNA topology and/ or chromosome domain organization. Chromosomes show different frequencies of nondisjunction (NDJ), reflecting inherent differences in meiotic crossover control, yet the underlying basis of these differences remains elusive. Here we show that a novel chromatin factor, X non-disjunction factor 1 (xnd-1), is responsible for the global distribution of COs in C. elegans. xnd-1 is also required for formation of double-strand breaks (DSBs) on the X, but surprisingly XND-1 protein is autosomally enriched. We show that xnd-1 functions independently of genes required for X chromosome-specific gene silencing, revealing a novel pathway that distinguishes the X from autosomes in the germ line, and further show that xnd-1 exerts its effects on COs, at least in part, by modulating levels of H2A lysine 5 acetylation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045774/" 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/PMC3045774/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wagner, Cynthia R -- Kuervers, Lynnette -- Baillie, David L -- Yanowitz, Judith L -- K01 AG031296/AG/NIA NIH HHS/ -- K01 AG031296-03/AG/NIA NIH HHS/ -- K01AG031296/AG/NIA NIH HHS/ -- England -- Nature. 2010 Oct 14;467(7317):839-43. doi: 10.1038/nature09429.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Carnegie Institution of Washington, Department of Embryology, Baltimore, Maryland 21218, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20944745" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Caenorhabditis elegans/*genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Chromatin/genetics/*metabolism ; Crossing Over, Genetic/*genetics ; DNA Breaks, Double-Stranded ; Female ; Germ Cells/metabolism ; Histone Acetyltransferases/genetics/metabolism ; Histones/chemistry/metabolism ; Lysine/metabolism ; Male ; Meiosis/*genetics ; Nondisjunction, Genetic/genetics ; X Chromosome/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 105
    Publication Date: 2010-02-05
    Description: Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) 〉or= 40 kg m(-2) or BMI standard deviation score 〉or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880448/" 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/PMC2880448/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walters, R G -- Jacquemont, S -- Valsesia, A -- de Smith, A J -- Martinet, D -- Andersson, J -- Falchi, M -- Chen, F -- Andrieux, J -- Lobbens, S -- Delobel, B -- Stutzmann, F -- El-Sayed Moustafa, J S -- Chevre, J-C -- Lecoeur, C -- Vatin, V -- Bouquillon, S -- Buxton, J L -- Boute, O -- Holder-Espinasse, M -- Cuisset, J-M -- Lemaitre, M-P -- Ambresin, A-E -- Brioschi, A -- Gaillard, M -- Giusti, V -- Fellmann, F -- Ferrarini, A -- Hadjikhani, N -- Campion, D -- Guilmatre, A -- Goldenberg, A -- Calmels, N -- Mandel, J-L -- Le Caignec, C -- David, A -- Isidor, B -- Cordier, M-P -- Dupuis-Girod, S -- Labalme, A -- Sanlaville, D -- Beri-Dexheimer, M -- Jonveaux, P -- Leheup, B -- Ounap, K -- Bochukova, E G -- Henning, E -- Keogh, J -- Ellis, R J -- Macdermot, K D -- van Haelst, M M -- Vincent-Delorme, C -- Plessis, G -- Touraine, R -- Philippe, A -- Malan, V -- Mathieu-Dramard, M -- Chiesa, J -- Blaumeiser, B -- Kooy, R F -- Caiazzo, R -- Pigeyre, M -- Balkau, B -- Sladek, R -- Bergmann, S -- Mooser, V -- Waterworth, D -- Reymond, A -- Vollenweider, P -- Waeber, G -- Kurg, A -- Palta, P -- Esko, T -- Metspalu, A -- Nelis, M -- Elliott, P -- Hartikainen, A-L -- McCarthy, M I -- Peltonen, L -- Carlsson, L -- Jacobson, P -- Sjostrom, L -- Huang, N -- Hurles, M E -- O'Rahilly, S -- Farooqi, I S -- Mannik, K -- Jarvelin, M-R -- Pattou, F -- Meyre, D -- Walley, A J -- Coin, L J M -- Blakemore, A I F -- Froguel, P -- Beckmann, J S -- 077014/Wellcome Trust/United Kingdom -- 079534/Wellcome Trust/United Kingdom -- 082390/Wellcome Trust/United Kingdom -- 089061/Wellcome Trust/United Kingdom -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- G0500539/Medical Research Council/United Kingdom -- G0600331/Medical Research Council/United Kingdom -- G0600331(77796)/Medical Research Council/United Kingdom -- G0900554/Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Feb 4;463(7281):671-5. doi: 10.1038/nature08727.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Genomic Medicine, Imperial College London, London W12 0NN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20130649" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Age of Onset ; Aging ; Body Mass Index ; Case-Control Studies ; Child ; *Chromosome Deletion ; Chromosomes, Human, Pair 16/*genetics ; Cognition Disorders/complications/genetics ; Cohort Studies ; Europe ; Female ; Genome-Wide Association Study ; Heterozygote ; Humans ; Inheritance Patterns/genetics ; Male ; Mutation/genetics ; Obesity/complications/*genetics/*physiopathology ; *Penetrance ; Reproducibility of Results ; Sex Characteristics ; Young Adult
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  • 106
    Publication Date: 2010-11-26
    Description: Glioblastoma (GBM) is among the most aggressive of human cancers. A key feature of GBMs is the extensive network of abnormal vasculature characterized by glomeruloid structures and endothelial hyperplasia. Yet the mechanisms of angiogenesis and the origin of tumour endothelial cells remain poorly defined. Here we demonstrate that a subpopulation of endothelial cells within glioblastomas harbour the same somatic mutations identified within tumour cells, such as amplification of EGFR and chromosome 7. We additionally demonstrate that the stem-cell-like CD133(+) fraction includes a subset of vascular endothelial-cadherin (CD144)-expressing cells that show characteristics of endothelial progenitors capable of maturation into endothelial cells. Extensive in vitro and in vivo lineage analyses, including single cell clonal studies, further show that a subpopulation of the CD133(+) stem-like cell fraction is multipotent and capable of differentiation along tumour and endothelial lineages, possibly via an intermediate CD133(+)/CD144(+) progenitor cell. The findings are supported by genetic studies of specific exons selected from The Cancer Genome Atlas, quantitative FISH and comparative genomic hybridization data that demonstrate identical genomic profiles in the CD133(+) tumour cells, their endothelial progenitor derivatives and mature endothelium. Exposure to the clinical anti-angiogenesis agent bevacizumab or to a gamma-secretase inhibitor as well as knockdown shRNA studies demonstrate that blocking VEGF or silencing VEGFR2 inhibits the maturation of tumour endothelial progenitors into endothelium but not the differentiation of CD133(+) cells into endothelial progenitors, whereas gamma-secretase inhibition or NOTCH1 silencing blocks the transition into endothelial progenitors. These data may provide new perspectives on the mechanisms of failure of anti-angiogenesis inhibitors currently in use. The lineage plasticity and capacity to generate tumour vasculature of the putative cancer stem cells within glioblastoma are novel findings that provide new insight into the biology of gliomas and the definition of cancer stemness, as well as the mechanisms of tumour neo-angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Rong -- Chadalavada, Kalyani -- Wilshire, Jennifer -- Kowalik, Urszula -- Hovinga, Koos E -- Geber, Adam -- Fligelman, Boris -- Leversha, Margaret -- Brennan, Cameron -- Tabar, Viviane -- England -- Nature. 2010 Dec 9;468(7325):829-33. doi: 10.1038/nature09624. Epub 2010 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21102433" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Animals ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized ; Antigens, CD/metabolism ; Bevacizumab ; Cadherins/deficiency/metabolism ; *Cell Differentiation ; Cell Line, Tumor ; Cell Lineage ; Chromosome Aberrations ; Coculture Techniques ; Endothelial Cells/metabolism/*pathology ; Female ; Glioblastoma/*blood supply/genetics/*pathology ; Glycoproteins/metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Integrin beta4/metabolism ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neovascularization, Pathologic/*pathology ; Neural Stem Cells/metabolism/*pathology ; Peptides/metabolism ; Receptor, Notch1/deficiency/genetics ; Vascular Endothelial Growth Factor A/antagonists & inhibitors
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  • 107
    Publication Date: 2010-10-01
    Description: The emphasis in cancer drug development has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted, rationally designed drugs promising greater efficacy and less side effects. Nevertheless, despite some successes drug development remains painfully slow. Here, we highlight the issues involved and suggest ways in which this process can be improved and expedited. We envision an increasing shift to integrated cancer research and biomarker-driven adaptive and hypothesis testing clinical trials. The goal is the development of specific cancer medicines to treat the individual patient, with treatment selection being driven by a detailed understanding of the genetics and biology of the patient and their cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Bono, J S -- Ashworth, Alan -- England -- Nature. 2010 Sep 30;467(7315):543-9. doi: 10.1038/nature09339.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG, UK. johann.de-bono@icr.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20882008" target="_blank"〉PubMed〈/a〉
    Keywords: Biomarkers, Tumor/antagonists & inhibitors/genetics/metabolism ; Biomedical Research/*trends ; Clinical Trials as Topic ; Drug Approval ; Drug Design ; Female ; Humans ; Male ; Models, Biological ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Precision Medicine/*trends ; Tissue Banks ; Translational Medical Research/*trends
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 108
    Publication Date: 2010-06-19
    Description: Glucocorticoids are widely used to treat patients with autoimmune diseases such as systemic lupus erythematosus (SLE). However, regimens used to treat many such conditions cannot maintain disease control in the majority of SLE patients and more aggressive approaches such as high-dose methylprednisolone pulse therapy are used to provide transient reductions in disease activity. The primary anti-inflammatory mechanism of glucocorticoids is thought to be NF-kappaB inhibition. Recognition of self nucleic acids by toll-like receptors TLR7 and TLR9 on B cells and plasmacytoid dendritic cells (PDCs) is an important step in the pathogenesis of SLE, promoting anti-nuclear antibodies and the production of type I interferon (IFN), both correlated with the severity of disease. Following their activation by self-nucleic acid-associated immune complexes, PDCs migrate to the tissues. We demonstrate, in vitro and in vivo, that stimulation of PDCs through TLR7 and 9 can account for the reduced activity of glucocorticoids to inhibit the IFN pathway in SLE patients and in two lupus-prone mouse strains. The triggering of PDCs through TLR7 and 9 by nucleic acid-containing immune complexes or by synthetic ligands activates the NF-kappaB pathway essential for PDC survival. Glucocorticoids do not affect NF-kappaB activation in PDCs, preventing glucocorticoid induction of PDC death and the consequent reduction of systemic IFN-alpha levels. These findings unveil a new role for self nucleic acid recognition by TLRs and indicate that inhibitors of TLR7 and 9 signalling could prove to be effective corticosteroid-sparing drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964153/" 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/PMC2964153/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guiducci, Cristiana -- Gong, Mei -- Xu, Zhaohui -- Gill, Michelle -- Chaussabel, Damien -- Meeker, Thea -- Chan, Jean H -- Wright, Tracey -- Punaro, Marilynn -- Bolland, Silvia -- Soumelis, Vassili -- Banchereau, Jacques -- Coffman, Robert L -- Pascual, Virginia -- Barrat, Franck J -- 2R44AI066483-02/AI/NIAID NIH HHS/ -- P50 AR054083/AR/NIAMS NIH HHS/ -- P50 AR054083-01/AR/NIAMS NIH HHS/ -- P50 AR054083-010001/AR/NIAMS NIH HHS/ -- P50 AR054083-010002/AR/NIAMS NIH HHS/ -- P50 AR054083-019001/AR/NIAMS NIH HHS/ -- P50 AR054083-02/AR/NIAMS NIH HHS/ -- P50 AR054083-020001/AR/NIAMS NIH HHS/ -- P50 AR054083-020002/AR/NIAMS NIH HHS/ -- P50 AR054083-029001/AR/NIAMS NIH HHS/ -- P50 AR054083-03/AR/NIAMS NIH HHS/ -- P50 AR054083-030001/AR/NIAMS NIH HHS/ -- P50 AR054083-030002/AR/NIAMS NIH HHS/ -- P50 AR054083-04/AR/NIAMS NIH HHS/ -- P50 AR054083-040001/AR/NIAMS NIH HHS/ -- P50 AR054083-040002/AR/NIAMS NIH HHS/ -- P50 AR054083-04S1/AR/NIAMS NIH HHS/ -- P50 AR054083-05/AR/NIAMS NIH HHS/ -- P50 AR054083-050001/AR/NIAMS NIH HHS/ -- P50 AR054083-050002/AR/NIAMS NIH HHS/ -- P50-ARO54083-01CORT/PHS HHS/ -- R44 AI066483/AI/NIAID NIH HHS/ -- R44 AI066483-02/AI/NIAID NIH HHS/ -- U19 AI082715/AI/NIAID NIH HHS/ -- U19 AI082715-01/AI/NIAID NIH HHS/ -- U19 AI082715-017348/AI/NIAID NIH HHS/ -- U19 AI082715-017351/AI/NIAID NIH HHS/ -- U19 AI082715-02/AI/NIAID NIH HHS/ -- U19 AI082715-027348/AI/NIAID NIH HHS/ -- U19 AI082715-027351/AI/NIAID NIH HHS/ -- U19 AI082715-03/AI/NIAID NIH HHS/ -- U19-AI082715-01/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):937-41. doi: 10.1038/nature09102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, California 94710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559388" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; Autoantibodies/immunology ; Cell Survival/drug effects ; Cells, Cultured ; Child ; Dendritic Cells/*drug effects ; Disease Models, Animal ; Female ; Glucocorticoids/*pharmacology ; Humans ; Interferon-alpha/immunology ; Interferons/immunology ; Lupus Erythematosus, Systemic/*physiopathology ; Male ; Membrane Glycoproteins/immunology ; Mice ; Mice, Inbred C57BL ; NF-kappa B/immunology ; Nucleic Acids/*immunology ; Toll-Like Receptor 7/*immunology ; Toll-Like Receptor 9/*immunology ; Up-Regulation
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 109
    Publication Date: 2010-12-03
    Description: Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037591/" 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/PMC3037591/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gurumurthy, Sushma -- Xie, Stephanie Z -- Alagesan, Brinda -- Kim, Judith -- Yusuf, Rushdia Z -- Saez, Borja -- Tzatsos, Alexandros -- Ozsolak, Fatih -- Milos, Patrice -- Ferrari, Francesco -- Park, Peter J -- Shirihai, Orian S -- Scadden, David T -- Bardeesy, Nabeel -- DK050234/DK/NIDDK NIH HHS/ -- R01 DK050234/DK/NIDDK NIH HHS/ -- R01 DK050234-12/DK/NIDDK NIH HHS/ -- R01 DK050234-13/DK/NIDDK NIH HHS/ -- R01 HG005230/HG/NHGRI NIH HHS/ -- R01 HG005230-01/HG/NHGRI NIH HHS/ -- U01 CA141576-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):659-63. doi: 10.1038/nature09572.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124451" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Apoptosis ; Autophagy ; Bone Marrow/metabolism/pathology ; Cell Cycle ; Cell Proliferation ; Cell Survival ; *Energy Metabolism ; Enzyme Activation ; Female ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism/pathology ; Homeostasis ; Lipid Metabolism ; Male ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism/pathology ; Multiprotein Complexes ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Proteins/antagonists & inhibitors/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Tumor Suppressor Proteins/deficiency/genetics/metabolism
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  • 110
    Publication Date: 2010-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kokko, Hanna -- Jennions, Michael -- England -- Nature. 2010 Apr 15;464(7291):990-1. doi: 10.1038/464990b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393552" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura/classification/*physiology ; *Ecosystem ; Female ; Food ; Fresh Water/*analysis ; Larva/physiology ; Male ; *Maternal Behavior/physiology ; *Paternal Behavior ; Phylogeny ; Survival Rate
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  • 111
    Publication Date: 2010-03-17
    Description: Demethylation at distinct lysine residues in histone H3 by lysine-specific demethylase 1 (LSD1) causes either gene repression or activation. As a component of co-repressor complexes, LSD1 contributes to target gene repression by removing mono- and dimethyl marks from lysine 4 of histone H3 (H3K4). In contrast, during androgen receptor (AR)-activated gene expression, LSD1 removes mono- and dimethyl marks from lysine 9 of histone H3 (H3K9). Yet, the mechanisms that control this dual specificity of demethylation are unknown. Here we show that phosphorylation of histone H3 at threonine 6 (H3T6) by protein kinase C beta I (PKCbeta(I), also known as PRKCbeta) is the key event that prevents LSD1 from demethylating H3K4 during AR-dependent gene activation. In vitro, histone H3 peptides methylated at lysine 4 and phosphorylated at threonine 6 are no longer LSD1 substrates. In vivo, PKCbeta(I) co-localizes with AR and LSD1 on target gene promoters and phosphorylates H3T6 after androgen-induced gene expression. RNA interference (RNAi)-mediated knockdown of PKCbeta(I) abrogates H3T6 phosphorylation, enhances demethylation at H3K4, and inhibits AR-dependent transcription. Activation of PKCbeta(I) requires androgen-dependent recruitment of the gatekeeper kinase protein kinase C (PKC)-related kinase 1 (PRK1). Notably, increased levels of PKCbeta(I) and phosphorylated H3T6 (H3T6ph) positively correlate with high Gleason scores of prostate carcinomas, and inhibition of PKCbeta(I) blocks AR-induced tumour cell proliferation in vitro and cancer progression of tumour xenografts in vivo. Together, our data establish that androgen-dependent kinase signalling leads to the writing of the new chromatin mark H3T6ph, which in consequence prevents removal of active methyl marks from H3K4 during AR-stimulated gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Metzger, Eric -- Imhof, Axel -- Patel, Dharmeshkumar -- Kahl, Philip -- Hoffmeyer, Katrin -- Friedrichs, Nicolaus -- Muller, Judith M -- Greschik, Holger -- Kirfel, Jutta -- Ji, Sujuan -- Kunowska, Natalia -- Beisenherz-Huss, Christian -- Gunther, Thomas -- Buettner, Reinhard -- Schule, Roland -- England -- Nature. 2010 Apr 1;464(7289):792-6. doi: 10.1038/nature08839. Epub 2010 Mar 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Urologische Klinik/Frauenklinik und Zentrale Klinische Forschung, Klinikum der Universitat Freiburg, Breisacherstrasse 66, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20228790" target="_blank"〉PubMed〈/a〉
    Keywords: Androgens/metabolism/pharmacology ; Animals ; Cell Division/drug effects ; Cell Line, Tumor ; Chromatin/metabolism ; Gene Expression Regulation/drug effects ; Gene Knockdown Techniques ; Histone Demethylases/antagonists & inhibitors/*metabolism ; Histones/*chemistry/*metabolism ; Humans ; Lysine/chemistry/metabolism ; Male ; Methylation/drug effects ; Mice ; Mice, Nude ; Mice, SCID ; Phosphorylation/drug effects ; Phosphothreonine/metabolism ; Promoter Regions, Genetic/genetics ; Prostatic Neoplasms/enzymology/metabolism/pathology ; Protein Kinase C/antagonists & inhibitors/deficiency/genetics/*metabolism ; Protein Kinase C beta ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
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  • 112
    Publication Date: 2010-11-12
    Description: Parkinson's disease is a pervasive, ageing-related neurodegenerative disease the cardinal motor symptoms of which reflect the loss of a small group of neurons, the dopaminergic neurons in the substantia nigra pars compacta (SNc). Mitochondrial oxidant stress is widely viewed as being responsible for this loss, but why these particular neurons should be stressed is a mystery. Here we show, using transgenic mice that expressed a redox-sensitive variant of green fluorescent protein targeted to the mitochondrial matrix, that the engagement of plasma membrane L-type calcium channels during normal autonomous pacemaking created an oxidant stress that was specific to vulnerable SNc dopaminergic neurons. The oxidant stress engaged defences that induced transient, mild mitochondrial depolarization or uncoupling. The mild uncoupling was not affected by deletion of cyclophilin D, which is a component of the permeability transition pore, but was attenuated by genipin and purine nucleotides, which are antagonists of cloned uncoupling proteins. Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson's disease, downregulated the expression of two uncoupling proteins (UCP4 (SLC25A27) and UCP5 (SLC25A14)), compromised calcium-induced uncoupling and increased oxidation of matrix proteins specifically in SNc dopaminergic neurons. Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465557/" 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/PMC4465557/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guzman, Jaime N -- Sanchez-Padilla, Javier -- Wokosin, David -- Kondapalli, Jyothisri -- Ilijic, Ema -- Schumacker, Paul T -- Surmeier, D James -- HL35440/HL/NHLBI NIH HHS/ -- K12GM088020/GM/NIGMS NIH HHS/ -- NS 054850/NS/NINDS NIH HHS/ -- NS047085/NS/NINDS NIH HHS/ -- P30 NS054850/NS/NINDS NIH HHS/ -- P50 NS047085/NS/NINDS NIH HHS/ -- R01 HL035440/HL/NHLBI NIH HHS/ -- R21 RR025355/RR/NCRR NIH HHS/ -- RR025355/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):696-700. doi: 10.1038/nature09536. Epub 2010 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068725" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*physiology ; Brain/cytology/metabolism ; Calcium/metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/metabolism/pharmacology ; Calcium Signaling ; Cyclophilins/metabolism ; Dihydropyridines/pharmacology ; Dopamine/*metabolism ; Gene Deletion ; Ion Channels/antagonists & inhibitors/metabolism ; Iridoid Glycosides/pharmacology ; Iridoids ; Male ; Mice ; Mice, Transgenic ; Mitochondria/metabolism ; Mitochondrial Proteins/antagonists & inhibitors/metabolism ; Neurons/cytology/*metabolism ; Oncogene Proteins/deficiency/genetics/*metabolism ; *Oxidative Stress ; Parkinson Disease/metabolism/pathology/prevention & control ; Peroxiredoxins ; Purines/pharmacology ; Superoxides/metabolism
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  • 113
    Publication Date: 2010-08-27
    Description: Sexual differences in the extent and type of parental care lie at the heart of sexual selection theory, and evolution resulting from parental conflict has produced some striking behavioural and morphological adaptations. In a study of male pregnancy in Gulf pipefish, Paczolt and Jones showed that more eggs were transferred to the male's brood pouch and more offspring survived following mating with large females (preferred by males) than with small (less preferred) females. Although the authors conclude that the lower survival of embryos from small females is most consistent with males actively removing resources from these offspring, no data are presented to directly support this hypothesis (ref. 2, and Supplementary Information therein) and the data do not refute the alternative explanation that differential egg survival is caused by female effects mediated by variation in fecundity and egg size or quality. We argue that only by experimentally manipulating female attractiveness separately from the quality of eggs deposited in the brood pouch can the extent of sexual conflict in this role-reversed system be assessed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gwynne, Darryl T -- Judge, Kevin A -- Kelly, Clint D -- England -- Nature. 2010 Aug 26;466(7310):E11; discussion E12. doi: 10.1038/nature09275.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada L5L 1C6. darryl.gwynne@utoronto.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20739960" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Size/physiology ; Clutch Size/physiology ; Embryo, Nonmammalian ; Female ; Male ; Reproduction/*physiology ; Sexual Behavior, Animal/physiology ; Smegmamorpha/*physiology ; Survival Rate
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  • 114
    Publication Date: 2010-10-29
    Description: Meiotic recombinations contribute to genetic diversity by yielding new combinations of alleles. Recently, high-resolution recombination maps were inferred from high-density single-nucleotide polymorphism (SNP) data using linkage disequilibrium (LD) patterns that capture historical recombination events. The use of these maps has been demonstrated by the identification of recombination hotspots and associated motifs, and the discovery that the PRDM9 gene affects the proportion of recombinations occurring at hotspots. However, these maps provide no information about individual or sex differences. Moreover, locus-specific demographic factors like natural selection can bias LD-based estimates of recombination rate. Existing genetic maps based on family data avoid these shortcomings, but their resolution is limited by relatively few meioses and a low density of markers. Here we used genome-wide SNP data from 15,257 parent-offspring pairs to construct the first recombination maps based on directly observed recombinations with a resolution that is effective down to 10 kilobases (kb). Comparing male and female maps reveals that about 15% of hotspots in one sex are specific to that sex. Although male recombinations result in more shuffling of exons within genes, female recombinations generate more new combinations of nearby genes. We discover novel associations between recombination characteristics of individuals and variants in the PRDM9 gene and we identify new recombination hotspots. Comparisons of our maps with two LD-based maps inferred from data of HapMap populations of Utah residents with ancestry from northern and western Europe (CEU) and Yoruba in Ibadan, Nigeria (YRI) reveal population differences previously masked by noise and map differences at regions previously described as targets of natural selection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Augustine -- Thorleifsson, Gudmar -- Gudbjartsson, Daniel F -- Masson, Gisli -- Sigurdsson, Asgeir -- Jonasdottir, Aslaug -- Walters, G Bragi -- Jonasdottir, Adalbjorg -- Gylfason, Arnaldur -- Kristinsson, Kari Th -- Gudjonsson, Sigurjon A -- Frigge, Michael L -- Helgason, Agnar -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- England -- Nature. 2010 Oct 28;467(7319):1099-103. doi: 10.1038/nature09525.〈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/20981099" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Chromosomes, Human/*genetics ; DNA-Binding Proteins/genetics ; Europe/ethnology ; Exons/genetics ; Female ; Genetics, Population ; Haplotypes/genetics ; Heterozygote ; Histone-Lysine N-Methyltransferase/genetics ; Humans ; Linkage Disequilibrium/genetics ; Male ; Meiosis/genetics ; Nigeria/ethnology ; Pedigree ; Polymorphism, Single Nucleotide/genetics ; Recombination, Genetic/*genetics ; Sample Size ; Selection, Genetic/genetics ; *Sex Characteristics ; Utah
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  • 115
    Publication Date: 2010-07-03
    Description: Various social behaviours in mice are regulated by chemical signals called pheromones that act through the vomeronasal system. Exocrine gland-secreting peptide 1 (ESP1) is a 7-kDa peptide that is released into male tear fluids and stimulates vomeronasal sensory neurons in female mice. Here, we describe the molecular and neural mechanisms that are involved in the decoding of ESP1 signals in the vomeronasal system, which leads to behavioural output in female mice. ESP1 is recognized by a specific vomeronasal receptor, V2Rp5, and the ligand-receptor interaction results in sex-specific signal transmission to the amygdaloid and hypothalamic nuclei via the accessory olfactory bulb. Consequently, ESP1 enhances female sexual receptive behaviour upon male mounting (lordosis), allowing successful copulation. In V2Rp5-deficient mice, ESP1 induces neither neural activation nor sexual behaviour. These findings show that ESP1 is a crucial male pheromone that regulates female reproductive behaviour through a specific receptor in the mouse vomeronasal system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haga, Sachiko -- Hattori, Tatsuya -- Sato, Toru -- Sato, Koji -- Matsuda, Soichiro -- Kobayakawa, Reiko -- Sakano, Hitoshi -- Yoshihara, Yoshihiro -- Kikusui, Takefumi -- Touhara, Kazushige -- England -- Nature. 2010 Jul 1;466(7302):118-22. doi: 10.1038/nature09142.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20596023" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/metabolism ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Neurons/metabolism ; Pheromones/*metabolism ; Proteins/*metabolism ; Proto-Oncogene Proteins c-fos/metabolism ; Receptors, Odorant/deficiency/genetics/*metabolism ; Receptors, Pheromone/deficiency/genetics/*metabolism ; Sexual Behavior, Animal/*physiology ; TRPC Cation Channels/deficiency ; Vomeronasal Organ/cytology/innervation/*metabolism
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  • 116
    Publication Date: 2010-06-05
    Description: The understanding of natural and sexual selection requires both field and laboratory studies to exploit the advantages and avoid the disadvantages of each approach. However, studies have tended to be polarized among the types of organisms studied, with vertebrates studied in the field and invertebrates in the lab. We used video monitoring combined with DNA profiling of all of the members of a wild population of field crickets across two generations to capture the factors predicting the reproductive success of males and females. The factors that predict a male's success in gaining mates differ from those that predict how many offspring he has. We confirm the fundamental prediction that males vary more in their reproductive success than females, and we find that females as well as males leave more offspring when they mate with more partners.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rodriguez-Munoz, R -- Bretman, A -- Slate, J -- Walling, C A -- Tregenza, T -- New York, N.Y. -- Science. 2010 Jun 4;328(5983):1269-72. doi: 10.1126/science.1188102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Ecology and Conservation, School of Biosciences, University of Exeter, Cornwall Campus, Penryn TR10 EZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20522773" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; Female ; *Genetic Fitness ; Gryllidae/*genetics/*physiology ; Male ; *Mating Preference, Animal ; Microsatellite Repeats ; Oviposition ; Reproduction ; *Selection, Genetic ; *Sex Characteristics ; Sexual Behavior, Animal ; Vocalization, Animal
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  • 117
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clutton-Brock, Tim -- Sheldon, Ben C -- New York, N.Y. -- Science. 2010 Mar 5;327(5970):1207-8. doi: 10.1126/science.1187796.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK. thcb@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203037" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; *Ecosystem ; Female ; Interdisciplinary Communication ; Male ; *Mammals/physiology ; Pan troglodytes/physiology ; *Primates/physiology ; Reproduction ; *Research ; Research Support as Topic ; Time Factors
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  • 118
    Publication Date: 2010-02-27
    Description: The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins), and the functional implications of their localization have been unclear. We combined nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy techniques and found that, in cardiomyocytes from healthy adult rats and mice, spatially confined beta2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional beta1ARs are distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heart failure, beta2ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Thus, the redistribution of beta(2)ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nikolaev, Viacheslav O -- Moshkov, Alexey -- Lyon, Alexander R -- Miragoli, Michele -- Novak, Pavel -- Paur, Helen -- Lohse, Martin J -- Korchev, Yuri E -- Harding, Sian E -- Gorelik, Julia -- 084064/Wellcome Trust/United Kingdom -- BB/D020875/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0500373/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1653-7. doi: 10.1126/science.1185988. Epub 2010 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Compartmentation ; Cell Membrane/*metabolism/ultrastructure ; Chronic Disease ; Cyclic AMP/*metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytosol/metabolism ; Fluorescence Resonance Energy Transfer ; Heart Failure/*metabolism/*pathology ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Microscopy/methods ; Myocytes, Cardiac/*metabolism/ultrastructure ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-1/genetics/metabolism ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Sarcolemma/*metabolism/ultrastructure ; Signal Transduction
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  • 119
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jewkes, Rachel -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):145-7. doi: 10.1126/science.1193794.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gender and Health Research Unit, Medical Research Council, Pretoria, 0001, South Africa. rjewkes@mrc.ac.za〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616253" target="_blank"〉PubMed〈/a〉
    Keywords: Domestic Violence/prevention & control/statistics & numerical data ; Dominance-Subordination ; Female ; HIV Infections/epidemiology/*prevention & control/transmission ; Health Policy ; Humans ; Incidence ; *Interpersonal Relations ; Male ; Prejudice ; Prevalence ; Risk Factors ; Risk-Taking ; Sex Factors ; Sex Offenses/statistics & numerical data ; Sexual Behavior ; South Africa/epidemiology ; *Women's Health ; Women's Rights
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  • 120
    Publication Date: 2010-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1298-9. doi: 10.1126/science.330.6009.1298.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127220" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/administration & dosage/pharmacology/*therapeutic use ; Deoxycytidine/administration & dosage/*analogs & ; derivatives/pharmacology/therapeutic use ; Drug Combinations ; Drug Costs ; Drug Resistance, Viral ; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Female ; HIV/drug effects ; HIV Infections/*prevention & control/transmission ; Homosexuality, Male ; Humans ; Male ; Medication Adherence ; Organophosphorus Compounds/administration & dosage/pharmacology/*therapeutic use ; Randomized Controlled Trials as Topic ; Transsexualism
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  • 121
    Publication Date: 2010-10-23
    Description: CD4(+)Foxp3(+) regulatory T (T(reg)) cells are important for maintaining immune tolerance. Understanding the molecular mechanism that regulates T(reg) differentiation will facilitate the development of effective therapeutic strategies against autoimmune diseases. We report here that the SUMO E3 ligase PIAS1 restricts the differentiation of natural T(reg) cells by maintaining a repressive chromatin state of the Foxp3 promoter. PIAS1 acts by binding to the Foxp3 promoter to recruit DNA methyltransferases and heterochromatin protein 1 for epigenetic modifications. Pias1 deletion caused promoter demethylation, reduced histone H3 methylation at Lys(9), and enhanced promoter accessibility. Consistently, Pias1(-/-) mice displayed an increased natural T(reg) cell population and were resistant to the development of experimental autoimmune encephalomyelitis. Our studies have identified an epigenetic mechanism that negatively regulates the differentiation of natural T(reg) cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043201/" 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/PMC3043201/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Bin -- Tahk, Samuel -- Yee, Kathleen M -- Fan, Guoping -- Shuai, Ke -- K01 AR52717-01/AR/NIAMS NIH HHS/ -- R01 AI063286/AI/NIAID NIH HHS/ -- R01 AI063286-05/AI/NIAID NIH HHS/ -- R01 GM085797/GM/NIGMS NIH HHS/ -- R01 GM085797-03/GM/NIGMS NIH HHS/ -- R01AI063286/AI/NIAID NIH HHS/ -- R01GM085797/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):521-5. doi: 10.1126/science.1193787.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology-Oncology, Department of Medicine, 11-934 Factor Building, 10833 Le Conte Avenue, University of California, Los Angeles, Los Angeles, CA 90095, USA. bliu@ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966256" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; CD4-Positive T-Lymphocytes/cytology ; Chromatin/metabolism ; DNA (Cytosine-5-)-Methyltransferase/metabolism ; DNA Methylation ; Encephalomyelitis, Autoimmune, Experimental/immunology ; *Epigenesis, Genetic ; Female ; Forkhead Transcription Factors/genetics ; Histones/metabolism ; Lymphopoiesis/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Promoter Regions, Genetic ; Protein Inhibitors of Activated STAT/*physiology ; Repressor Proteins/*physiology ; T-Lymphocytes, Regulatory/*cytology/immunology ; Ubiquitin-Protein Ligases/*physiology
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  • 122
    Publication Date: 2010-04-24
    Description: Children's reading achievement is influenced by genetics as well as by family and school environments. The importance of teacher quality as a specific school environmental influence on reading achievement is unknown. We studied first- and second-grade students in Florida from schools representing diverse environments. Comparison of monozygotic and dizygotic twins, differentiating genetic similarities of 100% and 50%, provided an estimate of genetic variance in reading achievement. Teacher quality was measured by how much reading gain the non-twin classmates achieved. The magnitude of genetic variance associated with twins' oral reading fluency increased as the quality of their teacher increased. In circumstances where the teachers are all excellent, the variability in student reading achievement may appear to be largely due to genetics. However, poor teaching impedes the ability of children to reach their potential.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2905841/" 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/PMC2905841/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, J -- Roehrig, A D -- Soden Hensler, B -- Connor, C M -- Schatschneider, C -- P50 HD052120/HD/NICHD NIH HHS/ -- P50 HD052120-02/HD/NICHD NIH HHS/ -- P50 HD052120-020003/HD/NICHD NIH HHS/ -- P50 HD052120-030003/HD/NICHD NIH HHS/ -- P50 HD052120-040003/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2010 Apr 23;328(5977):512-4. doi: 10.1126/science.1186149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Florida State University, Tallahassee, FL 32306-4301, USA. taylor@psy.fsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413504" target="_blank"〉PubMed〈/a〉
    Keywords: *Achievement ; Child ; *Educational Measurement ; *Educational Status ; Faculty/*standards ; Female ; Florida ; *Genes ; Humans ; Male ; *Reading ; Teaching/*standards ; Twins, Dizygotic ; Twins, Monozygotic
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  • 123
    Publication Date: 2010-10-12
    Description: Most hosts, including humans, are simultaneously or sequentially infected with several parasites. A key question is whether patterns of coinfection arise because infection by one parasite species affects susceptibility to others or because of inherent differences between hosts. We used time-series data from individual hosts in natural populations to analyze patterns of infection risk for a microparasite community, detecting large positive and negative effects of other infections. Patterns remain once variations in host susceptibility and exposure are accounted for. Indeed, effects are typically of greater magnitude, and explain more variation in infection risk, than the effects associated with host and environmental factors more commonly considered in disease studies. We highlight the danger of mistaken inference when considering parasite species in isolation rather than parasite communities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033556/" 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/PMC3033556/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Telfer, Sandra -- Lambin, Xavier -- Birtles, Richard -- Beldomenico, Pablo -- Burthe, Sarah -- Paterson, Steve -- Begon, Mike -- 070675/Z/03/Z/Wellcome Trust/United Kingdom -- 075202/Wellcome Trust/United Kingdom -- 075202/Z/04/Z/Wellcome Trust/United Kingdom -- 081705/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Oct 8;330(6001):243-6. doi: 10.1126/science.1190333.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK. s.telfer@abdn.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929776" target="_blank"〉PubMed〈/a〉
    Keywords: Anaplasma phagocytophilum/physiology ; Animals ; Animals, Wild/microbiology/parasitology/virology ; *Arvicolinae/microbiology/parasitology/virology ; Babesia microti ; Babesiosis/complications/immunology/parasitology/*veterinary ; Bartonella/physiology ; Bartonella Infections/complications/immunology/microbiology/*veterinary ; Cowpox/complications/immunology/*veterinary/virology ; Disease Susceptibility ; Ehrlichiosis/complications/immunology/microbiology/*veterinary ; Female ; Host-Pathogen Interactions ; Male ; *Microbial Interactions ; Risk Factors ; *Rodent Diseases/microbiology/parasitology/virology ; Seasons
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  • 124
    Publication Date: 2010-07-03
    Description: Gain-of-function mutations in Kir6.2 (KCNJ11), the pore-forming subunit of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel, cause neonatal diabetes. Many patients also suffer from hypotonia (weak and flaccid muscles) and balance problems. The diabetes arises from suppressed insulin secretion by overactive KATP channels in pancreatic beta-cells, but the source of the motor phenotype is unknown. By using mice carrying a human Kir6.2 mutation (Val59--〉Met59) targeted to either muscle or nerve, we show that analogous motor impairments originate in the central nervous system rather than in muscle or peripheral nerves. We also identify locomotor hyperactivity as a feature of KATP channel overactivity. These findings suggest that drugs targeted against neuronal, rather than muscle, KATP channels are needed to treat the motor deficits and that such drugs require high blood-brain barrier permeability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clark, Rebecca H -- McTaggart, James S -- Webster, Richard -- Mannikko, Roope -- Iberl, Michaela -- Sim, Xiu Li -- Rorsman, Patrik -- Glitsch, Maike -- Beeson, David -- Ashcroft, Frances M -- 084655/Wellcome Trust/United Kingdom -- G0701521/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):458-61. doi: 10.1126/science.1186146. Epub 2010 Jul 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20595581" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Ataxia/physiopathology ; Diabetes Mellitus/*genetics/metabolism/physiopathology ; Female ; Gene Targeting ; Humans ; Infant, Newborn ; Male ; Membrane Potentials ; Mice ; Mice, Transgenic ; Motor Activity ; Muscle Hypotonia/*genetics/metabolism/physiopathology ; Muscle Strength ; Muscles/*metabolism ; Neurons/*metabolism ; Patch-Clamp Techniques ; Postural Balance ; Potassium Channels, Inwardly Rectifying/*genetics/*metabolism ; Purkinje Cells/physiology ; Receptors, Drug/metabolism ; Sulfonylurea Receptors ; Syndrome
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  • 125
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nathans, Jeremy -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1625. doi: 10.1126/science.330.6011.1625-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21163997" target="_blank"〉PubMed〈/a〉
    Keywords: China ; *Family Planning Policy ; Female ; Humans ; Male ; *Population Growth ; Sex Ratio
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  • 126
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):170-1. doi: 10.1126/science.329.5988.170.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616267" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Cities ; *Disease Outbreaks ; Female ; HIV Infections/*epidemiology/prevention & control ; *Homeless Youth/statistics & numerical data ; Humans ; Male ; Organizations ; Prevalence ; Risk Factors ; Russia/epidemiology ; Ukraine/epidemiology
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  • 127
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):165-7. doi: 10.1126/science.329.5988.165.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616264" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; HIV Infections/complications/*prevention & control/transmission ; *Harm Reduction ; Humans ; Male ; Methadone/*administration & dosage ; Methadyl Acetate/administration & dosage ; Narcotics/*administration & dosage ; Needle-Exchange Programs ; Opioid-Related Disorders/*rehabilitation ; Russia/epidemiology ; Substance Abuse, Intravenous/complications/*rehabilitation ; Ukraine/epidemiology
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  • 128
    Publication Date: 2010-12-04
    Description: Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462359/" 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/PMC3462359/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saar, Brian G -- Freudiger, Christian W -- Reichman, Jay -- Stanley, C Michael -- Holtom, Gary R -- Xie, X Sunney -- 1R01EB010244-01/EB/NIBIB NIH HHS/ -- R01 EB010244/EB/NIBIB NIH HHS/ -- R01 EB010244-02/EB/NIBIB NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 3;330(6009):1368-70. doi: 10.1126/science.1197236.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21127249" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Cutaneous ; Animals ; Capillaries ; Dimethyl Sulfoxide/administration & dosage/pharmacokinetics ; Epidermis/chemistry/metabolism ; Erythrocytes/physiology ; Humans ; Imaging, Three-Dimensional ; Light ; Lipids ; Male ; Mice ; Mice, Nude ; Molecular Imaging/*methods ; Skin/blood supply/*chemistry/*metabolism ; Spectrum Analysis, Raman/*methods ; Time Factors ; Vitamin A/administration & dosage/pharmacokinetics ; Water
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  • 129
    Publication Date: 2010-08-07
    Description: Visual, acoustic, and olfactory stimuli associated with a highly charged emotional situation take on the affective qualities of that situation. Where the emotional meaning of a given sensory experience is stored is a matter of debate. We found that excitotoxic lesions of auditory, visual, or olfactory secondary sensory cortices impaired remote, but not recent, fear memories in rats. Amnesia was modality-specific and not due to an interference with sensory or emotional processes. In these sites, memory persistence was dependent on ongoing protein kinase Mzeta activity and was associated with an increased activity of layers II-IV, thus suggesting a synaptic strengthening of corticocortical connections. Lesions of the same areas left intact the memory of sensory stimuli not associated with any emotional charge. We propose that secondary sensory cortices support memory storage and retrieval of sensory stimuli that have acquired a behavioral salience with the experience.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sacco, Tiziana -- Sacchetti, Benedetto -- New York, N.Y. -- Science. 2010 Aug 6;329(5992):649-56. doi: 10.1126/science.1183165.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, University of Turin, Corso Raffaello 30, I-10125 Turin, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20689011" target="_blank"〉PubMed〈/a〉
    Keywords: Acoustic Stimulation ; Amnesia/physiopathology ; Amygdala/physiology ; Animals ; Auditory Cortex/*physiology ; Conditioning (Psychology) ; Early Growth Response Protein 1/genetics/metabolism ; *Emotions ; *Fear ; Habituation, Psychophysiologic ; Male ; Memory/*physiology ; Odors ; Olfactory Pathways/*physiology ; Photic Stimulation ; Protein Kinase C/antagonists & inhibitors/metabolism ; Rats ; Rats, Wistar ; Synapses/physiology ; Visual Cortex/*physiology
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  • 130
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-04-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Normile, Dennis -- New York, N.Y. -- Science. 2010 Apr 23;328(5977):422-4. doi: 10.1126/science.328.5977.422.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20413471" target="_blank"〉PubMed〈/a〉
    Keywords: *Attitude to Health ; Breast Neoplasms/epidemiology/prevention & control ; Cardiovascular Diseases/epidemiology/prevention & control ; China/epidemiology ; Diabetes Mellitus, Type 2/epidemiology/prevention & control ; Diet ; Female ; Health Care Reform ; Humans ; *Life Style ; Male ; Overweight/epidemiology/prevention & control ; *Preventive Health Services ; *Primary Prevention ; Smoking/adverse effects/epidemiology
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  • 131
    Publication Date: 2010-11-26
    Description: Ghrelin is a gastric peptide hormone that stimulates weight gain in vertebrates. The biological activities of ghrelin require octanoylation of the peptide on Ser(3), an unusual posttranslational modification that is catalyzed by the enzyme ghrelin O-acyltransferase (GOAT). Here, we describe the design, synthesis, and characterization of GO-CoA-Tat, a peptide-based bisubstrate analog that antagonizes GOAT. GO-CoA-Tat potently inhibits GOAT in vitro, in cultured cells, and in mice. Intraperitoneal administration of GO-CoA-Tat improves glucose tolerance and reduces weight gain in wild-type mice but not in ghrelin-deficient mice, supporting the concept that its beneficial metabolic effects are due specifically to GOAT inhibition. In addition to serving as a research tool for mapping ghrelin actions, GO-CoA-Tat may help pave the way for clinical targeting of GOAT in metabolic diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068526/" 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/PMC3068526/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barnett, Brad P -- Hwang, Yousang -- Taylor, Martin S -- Kirchner, Henriette -- Pfluger, Paul T -- Bernard, Vincent -- Lin, Yu-yi -- Bowers, Erin M -- Mukherjee, Chandrani -- Song, Woo-Jin -- Longo, Patti A -- Leahy, Daniel J -- Hussain, Mehboob A -- Tschop, Matthias H -- Boeke, Jef D -- Cole, Philip A -- P01 CA016519/CA/NCI NIH HHS/ -- P01 CA016519-35/CA/NCI NIH HHS/ -- P30 DK079637/DK/NIDDK NIH HHS/ -- P60 DK079637/DK/NIDDK NIH HHS/ -- P60 DK079637-05/DK/NIDDK NIH HHS/ -- R01 DK081472/DK/NIDDK NIH HHS/ -- R01 DK081472-01A1/DK/NIDDK NIH HHS/ -- R01 DK081472-02/DK/NIDDK NIH HHS/ -- R01 DK081472-03/DK/NIDDK NIH HHS/ -- R01 GM062437/GM/NIGMS NIH HHS/ -- R01 GM062437-04/GM/NIGMS NIH HHS/ -- R01 GM062437-11/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1689-92. doi: 10.1126/science.1196154. Epub 2010 Nov 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21097901" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Acyltransferases/*antagonists & inhibitors ; Animals ; Cell Survival/drug effects ; Drug Design ; Enzyme Inhibitors/chemical synthesis/*pharmacology/toxicity ; Ghrelin/deficiency/genetics/*metabolism ; Glucose/*metabolism ; Glucose Tolerance Test ; HeLa Cells ; Homeostasis ; Humans ; Insulin/metabolism ; Ion Channels/metabolism ; Islets of Langerhans/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondrial Proteins/metabolism ; Peptides/chemical synthesis/*pharmacology/toxicity ; Weight Gain/*drug effects
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  • 132
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rock, Jason R -- Hogan, Brigid L M -- R37 HL071303/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 24;329(5999):1610-1. doi: 10.1126/science.1196016.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929836" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/physiology ; Animals ; Carbachol/pharmacology ; Epithelium/embryology/innervation ; Ganglia, Parasympathetic/cytology/embryology/*physiology ; Humans ; Keratin-5/analysis ; Lung/embryology ; Male ; Mice ; Morphogenesis ; Multipotent Stem Cells/cytology/*physiology ; Neurons/*physiology ; Organogenesis ; Prostate/embryology ; Regeneration ; Submandibular Gland/cytology/*embryology/*innervation
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):160, 162-4. doi: 10.1126/science.329.5988.160.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616262" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/therapeutic use ; *Disease Outbreaks ; Europe, Eastern/epidemiology ; Female ; HIV Infections/complications/drug therapy/*epidemiology/prevention & control ; Harm Reduction ; Health Services Accessibility ; Humans ; Incidence ; Male ; Prevalence ; Russia/epidemiology ; Substance Abuse, Intravenous/complications/epidemiology ; Ukraine/epidemiology
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanderson, Warren C -- Scherbov, Sergei -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1287-8. doi: 10.1126/science.1193647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stony Brook University, Stony Brook, New York 11794, USA. warren.sanderson@stonybrook.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829469" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; *Aging ; Disabled Persons/*statistics & numerical data ; Female ; Forecasting ; *Health Status ; Humans ; *Life Expectancy/trends ; Male ; Policy Making ; *Population Dynamics
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  • 135
    Publication Date: 2010-08-14
    Description: Dendritic cells (DCs) play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens. However, the intracellular signaling networks that program DCs to become tolerogenic remain unknown. We report here that the Wnt-beta-catenin signaling in intestinal dendritic cells regulates the balance between inflammatory versus regulatory responses in the gut. beta-catenin in intestinal dendritic cells was required for the expression of anti-inflammatory mediators such as retinoic acid-metabolizing enzymes, interleukin-10, and transforming growth factor-beta, and the stimulation of regulatory T cell induction while suppressing inflammatory effector T cells. Furthermore, ablation of beta-catenin expression in DCs enhanced inflammatory responses and disease in a mouse model of inflammatory bowel disease. Thus, beta-catenin signaling programs DCs to a tolerogenic state, limiting the inflammatory response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732486/" 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/PMC3732486/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manicassamy, Santhakumar -- Reizis, Boris -- Ravindran, Rajesh -- Nakaya, Helder -- Salazar-Gonzalez, Rosa Maria -- Wang, Yi-Chong -- Pulendran, Bali -- HHSN266 200700006C/PHS HHS/ -- N01 AI50019/AI/NIAID NIH HHS/ -- N01 AI50025/AI/NIAID NIH HHS/ -- R01 AI048638/AI/NIAID NIH HHS/ -- R01 AI056499/AI/NIAID NIH HHS/ -- R01 DK057665/DK/NIDDK NIH HHS/ -- R01DK057665,/DK/NIDDK NIH HHS/ -- R37 AI048638/AI/NIAID NIH HHS/ -- R37 DK057665/DK/NIDDK NIH HHS/ -- R37AI48638,/AI/NIAID NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19AI057266,/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54AI057157/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):849-53. doi: 10.1126/science.1188510.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20705860" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytokines/metabolism ; Dendritic Cells/*immunology/metabolism ; Gene Expression Profiling ; *Inflammation ; Inflammatory Bowel Diseases/*immunology ; Intestinal Mucosa/cytology/*immunology/metabolism ; Macrophages/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; *Self Tolerance ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Tretinoin/metabolism ; Wnt Proteins/metabolism ; beta Catenin/*metabolism
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  • 136
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):35. doi: 10.1126/science.328.5974.35.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360084" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Databases, Nucleic Acid ; *Genome ; Male ; Pan troglodytes/*genetics ; Sequence Analysis, DNA
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  • 137
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-05-15
    Description: Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546315/" 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/PMC3546315/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorincz, Andrea -- Nusser, Zoltan -- 083484/Wellcome Trust/United Kingdom -- 090197/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 May 14;328(5980):906-9. doi: 10.1126/science.1187958.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary. lorincz@koki.hu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466935" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/chemistry/physiology ; CA1 Region, Hippocampal/*chemistry/physiology/ultrastructure ; Cell Membrane/chemistry ; Dendrites/*chemistry/physiology/ultrastructure ; Dendritic Spines/chemistry ; Fluorescent Antibody Technique ; Freeze Fracturing ; Immunohistochemistry ; Ion Channel Gating ; Male ; Microscopy, Immunoelectron ; NAV1.1 Voltage-Gated Sodium Channel ; NAV1.6 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins/analysis ; Ranvier's Nodes/chemistry ; Rats ; Rats, Wistar ; Sodium Channels/*analysis
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  • 138
    Publication Date: 2010-03-20
    Description: Differences in gene expression may play a major role in speciation and phenotypic diversity. We examined genome-wide differences in transcription factor (TF) binding in several humans and a single chimpanzee by using chromatin immunoprecipitation followed by sequencing. The binding sites of RNA polymerase II (PolII) and a key regulator of immune responses, nuclear factor kappaB (p65), were mapped in 10 lymphoblastoid cell lines, and 25 and 7.5% of the respective binding regions were found to differ between individuals. Binding differences were frequently associated with single-nucleotide polymorphisms and genomic structural variants, and these differences were often correlated with differences in gene expression, suggesting functional consequences of binding variation. Furthermore, comparing PolII binding between humans and chimpanzee suggests extensive divergence in TF binding. Our results indicate that many differences in individuals and species occur at the level of TF binding, and they provide insight into the genetic events responsible for these differences.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938768/" 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/PMC2938768/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kasowski, Maya -- Grubert, Fabian -- Heffelfinger, Christopher -- Hariharan, Manoj -- Asabere, Akwasi -- Waszak, Sebastian M -- Habegger, Lukas -- Rozowsky, Joel -- Shi, Minyi -- Urban, Alexander E -- Hong, Mi-Young -- Karczewski, Konrad J -- Huber, Wolfgang -- Weissman, Sherman M -- Gerstein, Mark B -- Korbel, Jan O -- Snyder, Michael -- R01 CA077808/CA/NCI NIH HHS/ -- R01 CA077808-09/CA/NCI NIH HHS/ -- T32 GM007205/GM/NIGMS NIH HHS/ -- T32 GM007205-34/GM/NIGMS NIH HHS/ -- T32GM07205/GM/NIGMS NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- U54 HG004558-04/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Apr 9;328(5975):232-5. doi: 10.1126/science.1183621. Epub 2010 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20299548" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Line ; Chromatin Immunoprecipitation ; DNA Copy Number Variations ; DNA, Intergenic ; Female ; *Gene Expression Regulation ; Humans ; Male ; Pan troglodytes/genetics ; *Polymorphism, Single Nucleotide ; Protein Binding ; RNA Polymerase II/genetics/*metabolism ; Sequence Analysis, DNA ; Species Specificity ; Transcription Factor RelA/genetics/*metabolism ; Transcription Initiation Site
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  • 139
    Publication Date: 2010-07-31
    Description: Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917982/" 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/PMC2917982/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldstein, Andrew S -- Huang, Jiaoti -- Guo, Changyong -- Garraway, Isla P -- Witte, Owen N -- GM07185/GM/NIGMS NIH HHS/ -- P50 CA092131/CA/NCI NIH HHS/ -- P50 CA092131-06/CA/NCI NIH HHS/ -- T32 GM007185/GM/NIGMS NIH HHS/ -- T32 GM007185-35/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):568-71. doi: 10.1126/science.1189992.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers, Tumor/metabolism ; Cell Separation ; *Cell Transformation, Neoplastic ; Epithelial Cells/metabolism/*pathology ; Epithelium/pathology ; Flow Cytometry ; Humans ; Keratins/analysis ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Prostate/cytology/metabolism/*pathology ; Prostatic Intraepithelial Neoplasia/metabolism/*pathology ; Prostatic Neoplasms/metabolism/*pathology ; Proto-Oncogene Proteins c-akt/metabolism ; Receptors, Androgen/metabolism ; Trans-Activators/metabolism ; Transduction, Genetic
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  • 140
    Publication Date: 2010-09-18
    Description: Proliferating cells, including cancer cells, require altered metabolism to efficiently incorporate nutrients such as glucose into biomass. The M2 isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic glycolysis and contributes to anabolic metabolism. Paradoxically, decreased pyruvate kinase enzyme activity accompanies the expression of PKM2 in rapidly dividing cancer cells and tissues. We demonstrate that phosphoenolpyruvate (PEP), the substrate for pyruvate kinase in cells, can act as a phosphate donor in mammalian cells because PEP participates in the phosphorylation of the glycolytic enzyme phosphoglycerate mutase (PGAM1) in PKM2-expressing cells. We used mass spectrometry to show that the phosphate from PEP is transferred to the catalytic histidine (His11) on human PGAM1. This reaction occurred at physiological concentrations of PEP and produced pyruvate in the absence of PKM2 activity. The presence of histidine-phosphorylated PGAM1 correlated with the expression of PKM2 in cancer cell lines and tumor tissues. Thus, decreased pyruvate kinase activity in PKM2-expressing cells allows PEP-dependent histidine phosphorylation of PGAM1 and may provide an alternate glycolytic pathway that decouples adenosine triphosphate production from PEP-mediated phosphotransfer, allowing for the high rate of glycolysis to support the anabolic metabolism observed in many proliferating cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030121/" 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/PMC3030121/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vander Heiden, Matthew G -- Locasale, Jason W -- Swanson, Kenneth D -- Sharfi, Hadar -- Heffron, Greg J -- Amador-Noguez, Daniel -- Christofk, Heather R -- Wagner, Gerhard -- Rabinowitz, Joshua D -- Asara, John M -- Cantley, Lewis C -- 1K08CA136983/CA/NCI NIH HHS/ -- 1P01CA120964-01A/CA/NCI NIH HHS/ -- 5 T32 CA009361-28/CA/NCI NIH HHS/ -- 5P30CA006516-43/CA/NCI NIH HHS/ -- K08 CA136983/CA/NCI NIH HHS/ -- K08 CA136983-02/CA/NCI NIH HHS/ -- P01 CA089021/CA/NCI NIH HHS/ -- P01 CA089021-10/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- P01 CA120964-01A1/CA/NCI NIH HHS/ -- P01 GM047467/GM/NIGMS NIH HHS/ -- P01 GM047467-20/GM/NIGMS NIH HHS/ -- P01CA089021/CA/NCI NIH HHS/ -- P01GM047467/GM/NIGMS NIH HHS/ -- P30 CA006516/CA/NCI NIH HHS/ -- P30 CA006516-43S1/CA/NCI NIH HHS/ -- R01 AI078063/AI/NIAID NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01-GM56302/GM/NIGMS NIH HHS/ -- R21 CA128620/CA/NCI NIH HHS/ -- R21/R33 DK070299/DK/NIDDK NIH HHS/ -- R33 DK070299/DK/NIDDK NIH HHS/ -- R33 DK070299-03/DK/NIDDK NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- T32 CA009361/CA/NCI NIH HHS/ -- T32 CA009361-28/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 17;329(5998):1492-9. doi: 10.1126/science.1188015.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20847263" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Cell Line ; Cell Line, Tumor ; *Cell Proliferation ; Female ; Glucose/*metabolism ; Glyceric Acids/metabolism ; *Glycolysis ; Histidine/metabolism ; Humans ; Isoenzymes/metabolism ; Kinetics ; Male ; Mammary Neoplasms, Animal/metabolism ; Mice ; Neoplasms/*metabolism/pathology ; Phosphoenolpyruvate/metabolism ; Phosphoglycerate Mutase/*metabolism ; Phosphopyruvate Hydratase/metabolism ; Phosphorylation ; Prostatic Neoplasms/metabolism ; Pyruvate Kinase/*metabolism ; Pyruvic Acid/metabolism ; Recombinant Proteins/metabolism
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  • 141
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1602. doi: 10.1126/science.330.6011.1602.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21163976" target="_blank"〉PubMed〈/a〉
    Keywords: *Early Detection of Cancer ; Genetic Predisposition to Disease ; *Genetic Testing ; *Genetic Variation ; Humans ; Male ; Precision Medicine ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms/*diagnosis
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  • 142
    Publication Date: 2010-05-08
    Description: Obesity results from chronic energy surplus and excess lipid storage in white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) efficiently burns lipids through adaptive thermogenesis. Studying mouse models, we show that cyclooxygenase (COX)-2, a rate-limiting enzyme in prostaglandin (PG) synthesis, is a downstream effector of beta-adrenergic signaling in WAT and is required for the induction of BAT in WAT depots. PG shifted the differentiation of defined mesenchymal progenitors toward a brown adipocyte phenotype. Overexpression of COX-2 in WAT induced de novo BAT recruitment in WAT, increased systemic energy expenditure, and protected mice against high-fat diet-induced obesity. Thus, COX-2 appears integral to de novo BAT recruitment, which suggests that the PG pathway regulates systemic energy homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vegiopoulos, Alexandros -- Muller-Decker, Karin -- Strzoda, Daniela -- Schmitt, Iris -- Chichelnitskiy, Evgeny -- Ostertag, Anke -- Berriel Diaz, Mauricio -- Rozman, Jan -- Hrabe de Angelis, Martin -- Nusing, Rolf M -- Meyer, Carola W -- Wahli, Walter -- Klingenspor, Martin -- Herzig, Stephan -- New York, N.Y. -- Science. 2010 May 28;328(5982):1158-61. doi: 10.1126/science.1186034. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emmy Noether and Marie Curie Research Group Molecular Metabolic Control, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448152" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes, Brown/cytology/*physiology ; Adipogenesis ; Adipose Tissue ; Adipose Tissue, Brown/cytology/*physiology ; Adipose Tissue, White/enzymology/*physiology ; Adrenergic beta-3 Receptor Agonists ; Adrenergic beta-Agonists/pharmacology ; Animals ; Body Weight ; Cyclooxygenase 2/*genetics/*metabolism ; Dietary Fats/administration & dosage ; Dioxoles/pharmacology ; *Energy Metabolism ; Female ; Gene Expression Regulation, Enzymologic ; Homeostasis ; Male ; Mesenchymal Stromal Cells/cytology ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mice, Transgenic ; Norepinephrine/metabolism ; Obesity/etiology/prevention & control ; Oxygen Consumption ; Prostaglandins/*metabolism ; Receptors, Adrenergic, beta-3/metabolism ; Signal Transduction ; *Thermogenesis
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  • 143
    Publication Date: 2010-06-05
    Description: The evolutionary appearance of p53 protein probably preceded its role in tumor suppression, suggesting that there may be unappreciated functions for this protein. Using genetic reporters as proxies to follow in vivo activation of the p53 network in Drosophila, we discovered that the process of meiotic recombination instigates programmed activation of p53 in the germ line. Specifically, double-stranded breaks in DNA generated by the topoisomerase Spo11 provoked functional p53 activity, which was prolonged in cells defective for meiotic DNA repair. This intrinsic stimulus for the p53 regulatory network is highly conserved because Spo11-dependent activation of p53 also occurs in mice. Our findings establish a physiological role for p53 in meiosis and suggest that tumor-suppressive functions may have been co-opted from primordial activities linked to recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917750/" 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/PMC2917750/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Wan-Jin -- Chapo, Joseph -- Roig, Ignasi -- Abrams, John M -- R01 AA017328/AA/NIAAA NIH HHS/ -- R01 AA017328-03/AA/NIAAA NIH HHS/ -- R01 AA017328-04/AA/NIAAA NIH HHS/ -- R01 GM072124/GM/NIGMS NIH HHS/ -- R01 GM072124-10/GM/NIGMS NIH HHS/ -- R01 GM072124-11/GM/NIGMS NIH HHS/ -- R01 GM072124-12/GM/NIGMS NIH HHS/ -- R01 GM072124-13/GM/NIGMS NIH HHS/ -- R01 GM072124-14A1/GM/NIGMS NIH HHS/ -- R01 GM072124-15/GM/NIGMS NIH HHS/ -- R01 HD040916/HD/NICHD NIH HHS/ -- R01 HD040916-09/HD/NICHD NIH HHS/ -- R01 HD040916-10/HD/NICHD NIH HHS/ -- R01AA017328/AA/NIAAA NIH HHS/ -- R01GM072124/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Jun 4;328(5983):1278-81. doi: 10.1126/science.1185640.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20522776" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; DNA/genetics/metabolism ; DNA Breaks, Double-Stranded ; DNA Damage ; DNA Helicases ; DNA Repair ; DNA Topoisomerases, Type II/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/embryology/*genetics/metabolism ; Egg Proteins/genetics/metabolism ; Embryo, Nonmammalian/metabolism ; Endodeoxyribonucleases ; Esterases/genetics/metabolism ; Female ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Genes, Insect ; *Genes, p53 ; Germ Cells/metabolism ; Male ; *Meiosis ; Mice ; Mice, Knockout ; Oogenesis ; *Recombination, Genetic ; Spermatocytes/physiology ; Tumor Suppressor Protein p53/genetics/*metabolism ; Ultraviolet Rays
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  • 144
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-10-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):440-3. doi: 10.1126/science.330.6003.440.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966228" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Antibodies, Neoplasm/immunology ; Clinical Trials as Topic ; Female ; Humans ; *Immunotherapy ; Male ; Melanoma/therapy ; Neoplasms/*therapy ; T-Lymphocytes/immunology
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  • 145
    Publication Date: 2010-05-01
    Description: All insects in the order Hymenoptera have haplodiploid sex determination, in which males emerge from haploid unfertilized eggs and females are diploid. Sex determination in the honeybee Apis mellifera is controlled by the complementary sex determination (csd) locus, but the mechanisms controlling sex determination in other Hymenoptera without csd are unknown. We identified the sex-determination system of the parasitic wasp Nasonia, which has no csd locus. Instead, maternal input of Nasonia vitripennis transformer (Nvtra) messenger RNA, in combination with specific zygotic Nvtra transcription, in which Nvtra autoregulates female-specific splicing, is essential for female development. Our data indicate that males develop as a result of maternal imprinting that prevents zygotic transcription of the maternally derived Nvtra allele in unfertilized eggs. Upon fertilization, zygotic Nvtra transcription is initiated, which autoregulates the female-specific transcript, leading to female development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Verhulst, Eveline C -- Beukeboom, Leo W -- van de Zande, Louis -- New York, N.Y. -- Science. 2010 Apr 30;328(5978):620-3. doi: 10.1126/science.1185805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Evolutionary Genetics, Centre for Ecological and Evolutionary Studies, University of Groningen, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20431014" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Diploidy ; Embryo, Nonmammalian/metabolism ; Female ; Fertilization ; *Gene Expression Regulation, Developmental ; Genes, Insect ; Genomic Imprinting ; *Haploidy ; Homeostasis ; Male ; *RNA Splicing ; RNA, Messenger/*genetics/metabolism ; *Sex Determination Processes ; *Transcription, Genetic ; Wasps/embryology/*genetics/physiology ; Zygote/physiology
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  • 146
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Travis, John -- New York, N.Y. -- Science. 2010 Oct 8;330(6001):172-3. doi: 10.1126/science.330.6001.172-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929754" target="_blank"〉PubMed〈/a〉
    Keywords: *Burial ; DNA/*analysis ; *Famous Persons ; Hair/*chemistry ; History, 19th Century ; Humans ; Indians, North American/*genetics/history ; Male ; Polymorphism, Single Nucleotide ; United States
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  • 147
    Publication Date: 2010-03-06
    Description: Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual's risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714868/" 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/PMC4714868/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vijay-Kumar, Matam -- Aitken, Jesse D -- Carvalho, Frederic A -- Cullender, Tyler C -- Mwangi, Simon -- Srinivasan, Shanthi -- Sitaraman, Shanthi V -- Knight, Rob -- Ley, Ruth E -- Gewirtz, Andrew T -- DK061417/DK/NIDDK NIH HHS/ -- DK06439/DK/NIDDK NIH HHS/ -- DK083275/DK/NIDDK NIH HHS/ -- K01 DK083275/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Apr 9;328(5975):228-31. doi: 10.1126/science.1179721. Epub 2010 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Emory University, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203013" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bacterial Physiological Phenomena ; Blood Glucose/analysis ; Body Fat Distribution ; Body Weight ; Caloric Restriction ; Dietary Fats/administration & dosage ; Female ; Germ-Free Life ; Hyperphagia/etiology ; *Immunity, Innate ; Insulin Resistance ; Intestinal Mucosa/immunology ; Intestines/*microbiology ; Male ; Metabolic Syndrome X/*etiology/immunology/microbiology ; Mice ; Mice, Knockout ; Obesity/etiology/immunology/microbiology/prevention & control ; Toll-Like Receptor 5/deficiency/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 148
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2010 Jun 25;328(5986):1619. doi: 10.1126/science.328.5986.1619.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Size ; Bone and Bones/*anatomy & histology ; Ethiopia ; Fossils ; *Hominidae/anatomy & histology/classification ; Male ; Paleontology ; Posture ; Skeleton ; Walking
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  • 149
    Publication Date: 2010-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):130-1. doi: 10.1126/science.327.5962.130.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20056859" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; C-Reactive Protein/analysis ; Cardiovascular Diseases/*prevention & control ; Female ; Fluorobenzenes/adverse effects/*therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects/*therapeutic use ; Male ; Pyrimidines/adverse effects/*therapeutic use ; Randomized Controlled Trials as Topic ; Rosuvastatin Calcium ; Sulfonamides/adverse effects/*therapeutic use ; United States ; United States Food and Drug Administration
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  • 150
    Publication Date: 2010-01-02
    Description: Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821451/" 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/PMC2821451/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parvanov, Emil D -- Petkov, Petko M -- Paigen, Kenneth -- 076468/PHS HHS/ -- 078452/PHS HHS/ -- 083408/PHS HHS/ -- CA 34196/CA/NCI NIH HHS/ -- GM 078643/GM/NIGMS NIH HHS/ -- P30 CA034196-26/CA/NCI NIH HHS/ -- P50 GM076468/GM/NIGMS NIH HHS/ -- P50 GM076468-030004/GM/NIGMS NIH HHS/ -- R01 GM078452/GM/NIGMS NIH HHS/ -- R01 GM078452-02/GM/NIGMS NIH HHS/ -- R01 GM078643/GM/NIGMS NIH HHS/ -- R01 GM078643-03/GM/NIGMS NIH HHS/ -- R01 GM083408/GM/NIGMS NIH HHS/ -- R01 GM083408-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):835. doi: 10.1126/science.1181495. Epub 2009 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Jackson Laboratory, Bar Harbor, ME 04609, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044538" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Chromosome Mapping ; Female ; Histone-Lysine N-Methyltransferase/chemistry/*genetics/metabolism ; Humans ; Male ; Meiosis/*genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; *Recombination, Genetic ; Sequence Analysis, DNA ; Testis/metabolism ; Zinc Fingers
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  • 151
    Publication Date: 2010-03-06
    Description: When selection favors sexual dimorphism, high-fitness parents often produce low-fitness progeny of the opposite sex. This sexual conflict is thought to overwhelm the genetic benefits of mate choice because preferred males incur a cost through the production of low-fitness daughters. We provide a counterpoint in a lizard (Anolis sagrei) that exhibits sexual conflict over body size. By using mate-choice experiments, we show that female brown anoles produce more sons than daughters via large sires but more daughters than sons via small sires. Measures of progeny fitness in the wild suggest that maximal fitness payoffs can be achieved by shifting offspring production from daughters to sons as sire size increases. These results illustrate how the resolution of sexual conflict can restore the genetic benefits of mate choice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cox, Robert M -- Calsbeek, Ryan -- New York, N.Y. -- Science. 2010 Apr 2;328(5974):92-4. doi: 10.1126/science.1185550. Epub 2010 Mar 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA. robert.m.cox@dartmouth.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Body Size ; Female ; *Genetic Fitness ; Lizards/anatomy & histology/*genetics/*physiology ; Male ; *Mating Preference, Animal ; Reproduction ; Selection, Genetic ; Sex Characteristics ; Sex Ratio ; Sexual Behavior, Animal
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  • 152
    Publication Date: 2010-05-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bolon, Brad -- Barthold, Stephen W -- Boyd, Kelli L -- Brayton, Cory -- Cardiff, Robert D -- Cork, Linda C -- Eaton, Kathryn A -- Schoeb, Trenton R -- Sundberg, John P -- Ward, Jerrold M -- U01 CA141582/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 May 28;328(5982):1103. doi: 10.1126/science.328.5982.1103-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20508110" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Experimentation ; Animals ; Bias (Epidemiology) ; *Biomedical Research ; Female ; Male ; Mice ; *Models, Animal ; Sex Characteristics
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  • 153
    Publication Date: 2010-07-10
    Description: Genomic imprinting results in preferential gene expression from paternally versus maternally inherited chromosomes. We used a genome-wide approach to uncover sex-specific parent-of-origin allelic effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Moreover, analysis of the cortex and hypothalamus identified 347 autosomal genes with sex-specific imprinting features. In the hypothalamus, sex-specific imprinted genes were mostly found in females, which suggests parental influence over the hypothalamic function of daughters. We show that interleukin-18, a gene linked to diseases with sex-specific prevalence, is subject to complex, regional, and sex-specific parental effects in the brain. Parent-of-origin effects thus provide new avenues for investigation of sexual dimorphism in brain function and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997643/" 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/PMC2997643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregg, Christopher -- Zhang, Jiangwen -- Butler, James E -- Haig, David -- Dulac, Catherine -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Aug 6;329(5992):682-5. doi: 10.1126/science.1190831. Epub 2010 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616234" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; Crosses, Genetic ; Dioxygenases ; *Epigenesis, Genetic ; Female ; Gene Expression Profiling ; *Genes, X-Linked ; *Genomic Imprinting ; Glutamic Acid/metabolism ; Interleukin-18/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondrial Proteins/genetics ; Neurons/metabolism ; Oxygenases/genetics ; Polymorphism, Single Nucleotide ; Prefrontal Cortex/cytology/*metabolism ; Preoptic Area/cytology/*metabolism ; Ribosomal Proteins/genetics ; *Sex Characteristics ; Succinate Dehydrogenase/genetics ; X Chromosome Inactivation
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  • 154
    Publication Date: 2010-07-10
    Description: Genomic imprinting results in preferential expression of the paternal or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain. This approach uncovered parent-of-origin allelic effects of more than 1300 loci. We identified parental bias in the expression of individual genes and of specific transcript isoforms, with differences between brain regions. Many imprinted genes are expressed in neural systems associated with feeding and motivated behaviors, and parental biases preferentially target genetic pathways governing metabolism and cell adhesion. We observed a preferential maternal contribution to gene expression in the developing brain and a major paternal contribution in the adult brain. Thus, parental expression bias emerges as a major mode of epigenetic regulation in the brain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005244/" 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/PMC3005244/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregg, Christopher -- Zhang, Jiangwen -- Weissbourd, Brandon -- Luo, Shujun -- Schroth, Gary P -- Haig, David -- Dulac, Catherine -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Aug 6;329(5992):643-8. doi: 10.1126/science.1190830. Epub 2010 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. cgregg@mcb.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616232" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Behavior, Animal ; Brain/*embryology/growth & development/*metabolism ; Epigenesis, Genetic ; Fathers ; Female ; *Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Silencing ; *Genomic Imprinting ; Male ; Mice ; Mothers ; Multigene Family ; Polymorphism, Single Nucleotide ; Prefrontal Cortex/embryology/growth & development/metabolism ; Preoptic Area/embryology/growth & development/metabolism ; Sex Characteristics
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  • 155
    Publication Date: 2010-09-18
    Description: Hybrids between species are often sterile or inviable because the long-diverged genomes of their parents cause developmental problems when they come together in a single individual. According to the Dobzhansky-Muller (DM) model, the number of genes involved in these "intrinsic postzygotic incompatibilities" should increase faster than linearly with the divergence time between species. This straightforward prediction of the DM model has remained contentious owing to a lack of explicit tests. Examining two pairs of Drosophila species, we show that the number of genes involved in postzygotic isolation increases at least as fast as the square of the number of substitutions (an index of divergence time) between species. This observation verifies a key prediction of the DM model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matute, Daniel R -- Butler, Ian A -- Turissini, David A -- Coyne, Jerry A -- R01GM058260/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 17;329(5998):1518-21. doi: 10.1126/science.1193440.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, The University of Chicago, 1101 East 57th Street, Chicago, IL 60637, USA. dmatute@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20847270" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Crosses, Genetic ; Drosophila/*genetics/physiology ; Drosophila melanogaster/genetics/physiology ; Epistasis, Genetic ; Female ; *Genes, Insect ; *Genetic Speciation ; *Hybridization, Genetic ; Infertility ; Male ; Models, Genetic ; Reproduction ; Species Specificity
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  • 156
    Publication Date: 2010-12-15
    Description: Alzheimer's disease is hypothesized to be caused by an imbalance between beta-amyloid (Abeta) production and clearance that leads to Abeta accumulation in the central nervous system (CNS). Abeta production and clearance are key targets in the development of disease-modifying therapeutic agents for Alzheimer's disease. However, there has not been direct evidence of altered Abeta production or clearance in Alzheimer's disease. By using metabolic labeling, we measured Abeta42 and Abeta40 production and clearance rates in the CNS of participants with Alzheimer's disease and cognitively normal controls. Clearance rates for both Abeta42 and Abeta40 were impaired in Alzheimer's disease compared with controls. On average, there were no differences in Abeta40 or Abeta42 production rates. Thus, the common late-onset form of Alzheimer's disease is characterized by an overall impairment in Abeta clearance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073454/" 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/PMC3073454/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mawuenyega, Kwasi G -- Sigurdson, Wendy -- Ovod, Vitaliy -- Munsell, Ling -- Kasten, Tom -- Morris, John C -- Yarasheski, Kevin E -- Bateman, Randall J -- K08 AG027091/AG/NIA NIH HHS/ -- K08 AG027091-03/AG/NIA NIH HHS/ -- K23 AG030946/AG/NIA NIH HHS/ -- K23 AG030946-04/AG/NIA NIH HHS/ -- P01 AG003991/AG/NIA NIH HHS/ -- P01 AG003991-28/AG/NIA NIH HHS/ -- P01 AG03991/AG/NIA NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30 DK056341-10/DK/NIDDK NIH HHS/ -- P41 GM103422/GM/NIGMS NIH HHS/ -- P41 RR000954/RR/NCRR NIH HHS/ -- P41 RR000954-34/RR/NCRR NIH HHS/ -- P50 AG005681/AG/NIA NIH HHS/ -- P50 AG005681-28/AG/NIA NIH HHS/ -- P50 AG05681/AG/NIA NIH HHS/ -- P60 DK020579/DK/NIDDK NIH HHS/ -- P60 DK020579-31/DK/NIDDK NIH HHS/ -- R01 NS065667/NS/NINDS NIH HHS/ -- R01 NS065667-03/NS/NINDS NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- UL1 RR024992-05/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 24;330(6012):1774. doi: 10.1126/science.1197623. Epub 2010 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148344" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Alzheimer Disease/cerebrospinal fluid/*metabolism ; Amyloid beta-Peptides/cerebrospinal fluid/*metabolism ; Brain/*metabolism ; Female ; Humans ; Kinetics ; Male ; Middle Aged ; Peptide Fragments/cerebrospinal fluid/*metabolism
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  • 157
    Publication Date: 2010-10-12
    Description: The maintenance of a progenitor cell population as a reservoir of undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial progenitor cells are maintained during organogenesis are poorly understood. We report that removal of the parasympathetic ganglion in mouse explant organ culture decreased the number and morphogenesis of keratin 5-positive epithelial progenitor cells. These effects were rescued with an acetylcholine analog. We demonstrate that acetylcholine signaling, via the muscarinic M1 receptor and epidermal growth factor receptor, increased epithelial morphogenesis and proliferation of the keratin 5-positive progenitor cells. Parasympathetic innervation maintained the epithelial progenitor cell population in an undifferentiated state, which was required for organogenesis. This mechanism for epithelial progenitor cell maintenance may be targeted for organ repair or regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376907/" 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/PMC3376907/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knox, S M -- Lombaert, I M A -- Reed, X -- Vitale-Cross, L -- Gutkind, J S -- Hoffman, M P -- Z99 DE999999/Intramural NIH HHS/ -- ZIA DE000707-08/Intramural NIH HHS/ -- ZIA DE000722-04/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 24;329(5999):1645-7. doi: 10.1126/science.1192046.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Matrix and Morphogenesis Unit, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929848" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Animals ; Carbachol/metabolism/pharmacology ; Cell Differentiation ; Epithelial Cells/cytology/*physiology ; Epithelium/embryology/innervation ; Ganglia, Parasympathetic/cytology/embryology/*physiology ; Heparin-binding EGF-like Growth Factor ; Intercellular Signaling Peptides and Proteins/metabolism/pharmacology ; Keratin-5/analysis/genetics ; Male ; Mice ; Morphogenesis/drug effects ; Neurons/cytology/*physiology ; Organ Culture Techniques ; *Organogenesis ; Prostate/cytology/embryology/innervation ; Quinazolines/pharmacology ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, Muscarinic M1/metabolism ; Regeneration ; Signal Transduction ; Stem Cells/cytology/*physiology ; Submandibular Gland/cytology/*embryology/*innervation
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  • 158
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-10-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):574-5. doi: 10.1126/science.330.6004.574.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21030618" target="_blank"〉PubMed〈/a〉
    Keywords: *DNA Copy Number Variations ; Databases, Nucleic Acid ; Female ; Gene Dosage ; *Gene Duplication ; Genes, Duplicate ; *Genetic Variation ; *Genome, Human ; Genome-Wide Association Study ; Genomics/*methods ; Humans ; Male ; Pilot Projects ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA
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  • 159
    Publication Date: 2010-01-09
    Description: Cocaine-induced alterations in gene expression cause changes in neuronal morphology and behavior that may underlie cocaine addiction. In mice, we identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the lysine dimethyltransferase G9a in cocaine-induced structural and behavioral plasticity. Repeated cocaine administration reduced global levels of H3K9 dimethylation in the nucleus accumbens. This reduction in histone methylation was mediated through the repression of G9a in this brain region, which was regulated by the cocaine-induced transcription factor DeltaFosB. Using conditional mutagenesis and viral-mediated gene transfer, we found that G9a down-regulation increased the dendritic spine plasticity of nucleus accumbens neurons and enhanced the preference for cocaine, thereby establishing a crucial role for histone methylation in the long-term actions of cocaine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820240/" 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/PMC2820240/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maze, Ian -- Covington, Herbert E 3rd -- Dietz, David M -- LaPlant, Quincey -- Renthal, William -- Russo, Scott J -- Mechanic, Max -- Mouzon, Ezekiell -- Neve, Rachael L -- Haggarty, Stephen J -- Ren, Yanhua -- Sampath, Srihari C -- Hurd, Yasmin L -- Greengard, Paul -- Tarakhovsky, Alexander -- Schaefer, Anne -- Nestler, Eric J -- P01 DA008227/DA/NIDA NIH HHS/ -- P01 DA008227-120001/DA/NIDA NIH HHS/ -- P01 DA008227-129001/DA/NIDA NIH HHS/ -- P01 DA008227-13/DA/NIDA NIH HHS/ -- P01 DA008227-14/DA/NIDA NIH HHS/ -- P01 DA008227-15/DA/NIDA NIH HHS/ -- P01 DA008227-16/DA/NIDA NIH HHS/ -- P01 DA008227-170003/DA/NIDA NIH HHS/ -- P01 DA008227-180003/DA/NIDA NIH HHS/ -- P01 DA010044/DA/NIDA NIH HHS/ -- P01 DA010044-14/DA/NIDA NIH HHS/ -- P01 DA010044-140005/DA/NIDA NIH HHS/ -- P01 DA010044-149002/DA/NIDA NIH HHS/ -- P01 DA010044-14S1/DA/NIDA NIH HHS/ -- P01 DA010044-14S10005/DA/NIDA NIH HHS/ -- P01 DA010044-14S19002/DA/NIDA NIH HHS/ -- P01 DA010044-15/DA/NIDA NIH HHS/ -- P01 DA010044-150005/DA/NIDA NIH HHS/ -- P01 DA010044-159002/DA/NIDA NIH HHS/ -- P01 DA08227/DA/NIDA NIH HHS/ -- P0110044/PHS HHS/ -- R01 DA007359/DA/NIDA NIH HHS/ -- R01 DA007359-02/DA/NIDA NIH HHS/ -- R01 DA007359-17/DA/NIDA NIH HHS/ -- R01 DA007359-18/DA/NIDA NIH HHS/ -- R01 DA007359-19/DA/NIDA NIH HHS/ -- R01 DA007359-20/DA/NIDA NIH HHS/ -- R01 DA007359-21/DA/NIDA NIH HHS/ -- R01 DA007359-22/DA/NIDA NIH HHS/ -- R01 DA014133/DA/NIDA NIH HHS/ -- R01 DA07359/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):213-6. doi: 10.1126/science.1179438.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20056891" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*drug effects ; Cocaine/*administration & dosage/pharmacology ; Cocaine-Related Disorders/etiology/metabolism ; Dendritic Spines/physiology ; Down-Regulation ; Enzyme Repression ; Gene Expression Profiling ; Gene Expression Regulation ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Histones/*metabolism ; Lysine/metabolism ; Male ; Methylation ; Mice ; Mice, Inbred C57BL ; *Neuronal Plasticity ; Neurons/drug effects/*metabolism ; Nucleus Accumbens/cytology/drug effects/*metabolism ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Reward ; Self Administration ; Transcription, Genetic
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  • 160
    Publication Date: 2010-07-22
    Description: The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime/boost combination increased the neutralization of diverse H1N1 strains dating from 1934 to 2007 as compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for the development of a universal influenza vaccine for humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wei, Chih-Jen -- Boyington, Jeffrey C -- McTamney, Patrick M -- Kong, Wing-Pui -- Pearce, Melissa B -- Xu, Ling -- Andersen, Hanne -- Rao, Srinivas -- Tumpey, Terrence M -- Yang, Zhi-Yong -- Nabel, Gary J -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1060-4. doi: 10.1126/science.1192517. Epub 2010 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892-3005, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647428" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/biosynthesis/*immunology ; Antibodies, Viral/biosynthesis/*immunology ; *Cross Protection ; Female ; Ferrets ; Genetic Vectors ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/*immunology ; Humans ; Immunization, Secondary ; Influenza A Virus, H1N1 Subtype/*immunology ; Influenza A Virus, H2N2 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza A Virus, H5N1 Subtype/immunology ; Influenza Vaccines/*administration & dosage/*immunology ; Influenza, Human/immunology/prevention & control ; Macaca mulatta ; Male ; Mice ; Mice, Inbred BALB C ; Mutant Proteins/immunology ; Orthomyxoviridae Infections/immunology/prevention & control ; Plasmids ; Vaccination ; Vaccines, DNA/administration & dosage/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 161
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 2010 Dec 17;330(6011):1605-7. doi: 10.1126/science.330.6011.1605.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21163979" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-HIV Agents/administration & dosage/therapeutic use ; Female ; Genetic Diseases, Inborn/genetics ; Genetic Engineering ; Genetic Techniques ; Genomics ; HIV Infections/prevention & control ; Hominidae/genetics ; Humans ; Induced Pluripotent Stem Cells ; Male ; Molecular Dynamics Simulation ; Physical Phenomena ; Rats/genetics ; *Science ; Sequence Analysis, DNA ; Synthetic Biology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 162
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-03-13
    Description: Hamilton's theory of inclusive fitness showed how natural selection could lead to behaviors that decrease the relative fitness of the actor and also either benefit (altruism) or harm (spite) other individuals. However, several fundamental issues in the evolution of altruism and spite have remained contentious. Here, we show how recent work has resolved three key debates, helping clarify how Hamilton's theoretical overview links to real-world examples, in organisms ranging from bacteria to humans: Is the evolution of extreme altruism, represented by the sterile workers of social insects, driven by genetics or ecology? Does spite really exist in nature? And, can altruism be favored between individuals who are not close kin but share a "greenbeard" gene for altruism?〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉West, Stuart A -- Gardner, Andy -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1341-4. doi: 10.1126/science.1178332.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, Oxford University, South Parks Road, Oxford OX1 3PS, UK. stuart.west@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223978" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; *Altruism ; Animals ; Behavior, Animal ; Competitive Behavior ; Cooperative Behavior ; Diploidy ; Female ; Genes ; *Genetic Fitness ; Haploidy ; Humans ; Male ; Reproduction ; *Selection, Genetic ; Sexual Behavior, Animal ; *Social Behavior
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 163
    Publication Date: 2010-01-16
    Description: We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849982/" 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/PMC2849982/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Werren, John H -- Richards, Stephen -- Desjardins, Christopher A -- Niehuis, Oliver -- Gadau, Jurgen -- Colbourne, John K -- Nasonia Genome Working Group -- Beukeboom, Leo W -- Desplan, Claude -- Elsik, Christine G -- Grimmelikhuijzen, Cornelis J P -- Kitts, Paul -- Lynch, Jeremy A -- Murphy, Terence -- Oliveira, Deodoro C S G -- Smith, Christopher D -- van de Zande, Louis -- Worley, Kim C -- Zdobnov, Evgeny M -- Aerts, Maarten -- Albert, Stefan -- Anaya, Victor H -- Anzola, Juan M -- Barchuk, Angel R -- Behura, Susanta K -- Bera, Agata N -- Berenbaum, May R -- Bertossa, Rinaldo C -- Bitondi, Marcia M G -- Bordenstein, Seth R -- Bork, Peer -- Bornberg-Bauer, Erich -- Brunain, Marleen -- Cazzamali, Giuseppe -- Chaboub, Lesley -- Chacko, Joseph -- Chavez, Dean -- Childers, Christopher P -- Choi, Jeong-Hyeon -- Clark, Michael E -- Claudianos, Charles -- Clinton, Rochelle A -- Cree, Andrew G -- Cristino, Alexandre S -- Dang, Phat M -- Darby, Alistair C -- de Graaf, Dirk C -- Devreese, Bart -- Dinh, Huyen H -- Edwards, Rachel -- Elango, Navin -- Elhaik, Eran -- Ermolaeva, Olga -- Evans, Jay D -- Foret, Sylvain -- Fowler, Gerald R -- Gerlach, Daniel -- Gibson, Joshua D -- Gilbert, Donald G -- Graur, Dan -- Grunder, Stefan -- Hagen, Darren E -- Han, Yi -- Hauser, Frank -- Hultmark, Da -- Hunter, Henry C 4th -- Hurst, Gregory D D -- Jhangian, Shalini N -- Jiang, Huaiyang -- Johnson, Reed M -- Jones, Andrew K -- Junier, Thomas -- Kadowaki, Tatsuhiko -- Kamping, Albert -- Kapustin, Yuri -- Kechavarzi, Bobak -- Kim, Jaebum -- Kim, Jay -- Kiryutin, Boris -- Koevoets, Tosca -- Kovar, Christie L -- Kriventseva, Evgenia V -- Kucharski, Robert -- Lee, Heewook -- Lee, Sandra L -- Lees, Kristin -- Lewis, Lora R -- Loehlin, David W -- Logsdon, John M Jr -- Lopez, Jacqueline A -- Lozado, Ryan J -- Maglott, Donna -- Maleszka, Ryszard -- Mayampurath, Anoop -- Mazur, Danielle J -- McClure, Marcella A -- Moore, Andrew D -- Morgan, Margaret B -- Muller, Jean -- Munoz-Torres, Monica C -- Muzny, Donna M -- Nazareth, Lynne V -- Neupert, Susanne -- Nguyen, Ngoc B -- Nunes, Francis M F -- Oakeshott, John G -- Okwuonu, Geoffrey O -- Pannebakker, Bart A -- Pejaver, Vikas R -- Peng, Zuogang -- Pratt, Stephen C -- Predel, Reinhard -- Pu, Ling-Ling -- Ranson, Hilary -- Raychoudhury, Rhitoban -- Rechtsteiner, Andreas -- Reese, Justin T -- Reid, Jeffrey G -- Riddle, Megan -- Robertson, Hugh M -- Romero-Severson, Jeanne -- Rosenberg, Miriam -- Sackton, Timothy B -- Sattelle, David B -- Schluns, Helge -- Schmitt, Thomas -- Schneider, Martina -- Schuler, Andreas -- Schurko, Andrew M -- Shuker, David M -- Simoes, Zila L P -- Sinha, Saurabh -- Smith, Zachary -- Solovyev, Victor -- Souvorov, Alexandre -- Springauf, Andreas -- Stafflinger, Elisabeth -- Stage, Deborah E -- Stanke, Mario -- Tanaka, Yoshiaki -- Telschow, Arndt -- Trent, Carol -- Vattathil, Selina -- Verhulst, Eveline C -- Viljakainen, Lumi -- Wanner, Kevin W -- Waterhouse, Robert M -- Whitfield, James B -- Wilkes, Timothy E -- Williamson, Michael -- Willis, Judith H -- Wolschin, Florian -- Wyder, Stefan -- Yamada, Takuji -- Yi, Soojin V -- Zecher, Courtney N -- Zhang, Lan -- Gibbs, Richard A -- 5R01GM070026-04/GM/NIGMS NIH HHS/ -- 5R01HG000747-14/HG/NHGRI NIH HHS/ -- 5R24GM084917-02/GM/NIGMS NIH HHS/ -- AI028309-13A2/AI/NIAID NIH HHS/ -- R01 AI055624/AI/NIAID NIH HHS/ -- R01 GM064864/GM/NIGMS NIH HHS/ -- R01 GM064864-04/GM/NIGMS NIH HHS/ -- R01 GM064864-05A2/GM/NIGMS NIH HHS/ -- R01 GM070026/GM/NIGMS NIH HHS/ -- R01 GM070026-04S1/GM/NIGMS NIH HHS/ -- R01 GM079484/GM/NIGMS NIH HHS/ -- R01 GM085163/GM/NIGMS NIH HHS/ -- R01 GM085163-01/GM/NIGMS NIH HHS/ -- R01 GM085233/GM/NIGMS NIH HHS/ -- R01 HG000747/HG/NHGRI NIH HHS/ -- R01 HG000747-14/HG/NHGRI NIH HHS/ -- R01GM064864/GM/NIGMS NIH HHS/ -- R24 GM084917/GM/NIGMS NIH HHS/ -- R24 GM084917-01/GM/NIGMS NIH HHS/ -- R24 GM084917-02/GM/NIGMS NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273-03/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):343-8. doi: 10.1126/science.1178028.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075255" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthropods/parasitology ; *Biological Evolution ; DNA Methylation ; DNA Transposable Elements ; Female ; Gene Transfer, Horizontal ; Genes, Insect ; Genetic Speciation ; Genetic Variation ; *Genome, Insect ; Host-Parasite Interactions ; Insect Proteins/genetics/metabolism ; Insect Viruses/genetics ; Insects/genetics ; Male ; Molecular Sequence Data ; Quantitative Trait Loci ; Recombination, Genetic ; Sequence Analysis, DNA ; Wasp Venoms/chemistry/toxicity ; Wasps/*genetics/physiology ; Wolbachia/genetics
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  • 164
    Publication Date: 2010-06-12
    Description: Humans regulate intergroup conflict through parochial altruism; they self-sacrifice to contribute to in-group welfare and to aggress against competing out-groups. Parochial altruism has distinct survival functions, and the brain may have evolved to sustain and promote in-group cohesion and effectiveness and to ward off threatening out-groups. Here, we have linked oxytocin, a neuropeptide produced in the hypothalamus, to the regulation of intergroup conflict. In three experiments using double-blind placebo-controlled designs, male participants self-administered oxytocin or placebo and made decisions with financial consequences to themselves, their in-group, and a competing out-group. Results showed that oxytocin drives a "tend and defend" response in that it promoted in-group trust and cooperation, and defensive, but not offensive, aggression toward competing out-groups.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Dreu, Carsten K W -- Greer, Lindred L -- Handgraaf, Michel J J -- Shalvi, Shaul -- Van Kleef, Gerben A -- Baas, Matthijs -- Ten Velden, Femke S -- Van Dijk, Eric -- Feith, Sander W W -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1408-11. doi: 10.1126/science.1189047.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, University of Amsterdam, Roetersstraat 15, 1018 WB Amsterdam, Netherlands. c.k.w.dedreu@uva.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20538951" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression/*drug effects ; *Altruism ; *Conflict (Psychology) ; Cooperative Behavior ; Decision Making ; Double-Blind Method ; Game Theory ; *Group Processes ; Humans ; Interpersonal Relations ; Male ; Oxytocin/administration & dosage/*pharmacology ; Trust ; Young Adult
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  • 165
    Publication Date: 2010-09-18
    Description: Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kranendijk, Martijn -- Struys, Eduard A -- van Schaftingen, Emile -- Gibson, K Michael -- Kanhai, Warsha A -- van der Knaap, Marjo S -- Amiel, Jeanne -- Buist, Neil R -- Das, Anibh M -- de Klerk, Johannis B -- Feigenbaum, Annette S -- Grange, Dorothy K -- Hofstede, Floris C -- Holme, Elisabeth -- Kirk, Edwin P -- Korman, Stanley H -- Morava, Eva -- Morris, Andrew -- Smeitink, Jan -- Sukhai, Ram N -- Vallance, Hilary -- Jakobs, Cornelis -- Salomons, Gajja S -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):336. doi: 10.1126/science.1192632. Epub 2010 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolic Unit, Department of Clinical Chemistry, VU University Medical Center, 1081 HV Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20847235" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Brain Diseases, Metabolic, Inborn/*genetics ; Brain Neoplasms/genetics/metabolism ; Child ; Child, Preschool ; Female ; *Germ-Line Mutation ; Glutarates/*metabolism/urine ; Heterozygote ; Humans ; Infant ; Isocitrate Dehydrogenase/chemistry/*genetics/metabolism ; Male ; Neoplasms/genetics/metabolism ; Young Adult
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  • 166
    Publication Date: 2010-09-11
    Description: Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135376/" 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/PMC3135376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dosenbach, Nico U F -- Nardos, Binyam -- Cohen, Alexander L -- Fair, Damien A -- Power, Jonathan D -- Church, Jessica A -- Nelson, Steven M -- Wig, Gagan S -- Vogel, Alecia C -- Lessov-Schlaggar, Christina N -- Barnes, Kelly Anne -- Dubis, Joseph W -- Feczko, Eric -- Coalson, Rebecca S -- Pruett, John R Jr -- Barch, Deanna M -- Petersen, Steven E -- Schlaggar, Bradley L -- DA027046/DA/NIDA NIH HHS/ -- EY16336/EY/NEI NIH HHS/ -- HD057076/HD/NICHD NIH HHS/ -- MH62130/MH/NIMH NIH HHS/ -- NS00169011/NS/NINDS NIH HHS/ -- NS053425/NS/NINDS NIH HHS/ -- NS32979/NS/NINDS NIH HHS/ -- NS41255/NS/NINDS NIH HHS/ -- NS46424/NS/NINDS NIH HHS/ -- NS51281/NS/NINDS NIH HHS/ -- NS55582/NS/NINDS NIH HHS/ -- R01 HD057076/HD/NICHD NIH HHS/ -- R01 HD057076-04/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1358-61. doi: 10.1126/science.1194144.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. ndosenbach@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829489" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aging ; Algorithms ; Artificial Intelligence ; Brain/*growth & development/*physiology ; Brain Mapping ; Cerebellum/growth & development/physiology ; Child ; Female ; Frontal Lobe/growth & development/physiology ; Humans ; *Magnetic Resonance Imaging ; Male ; Multivariate Analysis ; Neural Pathways ; Occipital Lobe/growth & development/physiology ; Young Adult
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 167
    Publication Date: 2010-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whiten, Andrew -- McGrew, William C -- Aiello, Leslie C -- Boesch, Christophe -- Boyd, Robert -- Byrne, Richard W -- Dunbar, Robin I M -- Matsuzawa, Tetsuro -- Silk, Joan B -- Tomasello, Michael -- van Schaik, Carel P -- Wrangham, Richard -- New York, N.Y. -- Science. 2010 Jan 22;327(5964):410; author reply 410-1. doi: 10.1126/science.327.5964.410-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20093456" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior ; Behavior, Animal ; *Biological Evolution ; Cognition ; Female ; *Hominidae/classification ; Humans ; Male ; *Pan troglodytes/classification
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  • 168
    Publication Date: 2010-01-16
    Description: Over the past two decades, HIV resistance to antiretroviral drugs (ARVs) has risen to high levels in the wealthier countries of the world, which are able to afford widespread treatment. We have gained insights into the evolution and transmission dynamics of ARV resistance by designing a biologically complex multistrain network model. With this model, we traced the evolutionary history of ARV resistance in San Francisco and predict its future dynamics. By using classification and regression trees, we identified the key immunologic, virologic, and treatment factors that increase ARV resistance. Our modeling shows that 60% of the currently circulating ARV-resistant strains in San Francisco are capable of causing self-sustaining epidemics, because each individual infected with one of these strains can cause, on average, more than one new resistant infection. It is possible that a new wave of ARV-resistant strains that pose a substantial threat to global public health is emerging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Robert J -- Okano, Justin T -- Kahn, James S -- Bodine, Erin N -- Blower, Sally -- K24RR024369/RR/NCRR NIH HHS/ -- P30-AI27763/AI/NIAID NIH HHS/ -- R01 AI041935/AI/NIAID NIH HHS/ -- R18-HS017784/HS/AHRQ HHS/ -- New York, N.Y. -- Science. 2010 Feb 5;327(5966):697-701. doi: 10.1126/science.1180556. Epub 2010 Jan 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Biomedical Modeling, Semel Institute of Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075214" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-HIV Agents/*pharmacology/therapeutic use ; Antiretroviral Therapy, Highly Active ; Computer Simulation ; Disease Outbreaks ; Drug Resistance, Multiple, Viral ; *Drug Resistance, Viral ; Drug Therapy, Combination ; Evolution, Molecular ; Forecasting ; HIV/*drug effects/genetics ; HIV Infections/drug therapy/epidemiology/*transmission/*virology ; HIV Protease Inhibitors/pharmacology/therapeutic use ; Homosexuality, Male ; Humans ; Male ; Models, Statistical ; Monte Carlo Method ; Probability ; Reverse Transcriptase Inhibitors/pharmacology/therapeutic use ; San Francisco/epidemiology
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  • 169
    Publication Date: 2010-03-20
    Description: Queens of ants and bees normally obtain a lifetime supply of sperm on a single day of sexual activity, and sperm competition is expected to occur in lineages where queens receive sperm from multiple males. We compared singly mated (monandrous) and multiply mated (polyandrous) sister groups of ants and bees and show that seminal fluid of polyandrous species has a more positive effect on the survival of a male's own sperm than on other males' sperm. This difference was not observed in the monandrous species, suggesting that incapacitation of competing sperm may have independently evolved in both bees and ants. In Atta leafcutter ants, the negative effect of the seminal fluid of other males was negated by secretion from the queen sperm-storage organ, suggesting that queens may control ejaculate competition after sperm storage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉den Boer, Susanne P A -- Baer, Boris -- Boomsma, Jacobus J -- New York, N.Y. -- Science. 2010 Mar 19;327(5972):1506-9. doi: 10.1126/science.1184709.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Social Evolution, Department of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20299595" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ants/*physiology ; Bees/*physiology ; Cell Survival ; Female ; Fertilization ; Genitalia, Female/physiology ; Genitalia, Male/physiology ; Male ; Reproduction ; Semen/*chemistry/*physiology ; *Sexual Behavior, Animal ; Spermatozoa/*physiology
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  • 170
    Publication Date: 2010-07-22
    Description: Genetic crosses in many organisms have shown that alleles of unlinked genes generally assort independently of one another during gamete formation. However, variation in chromosome size may affect the process of meiosis and lead to nonindependent assortment of chromosomes. We therefore examined chromosomes with insertions and found that they preferentially segregated away from the X chromosome during meiosis in Caenorhabditis elegans males. Conversely, chromosomes with deletions preferentially segregated with the X chromosome. The degree of segregation bias was significantly associated with the length of the insertion or deletion. Simulations revealed that this segregation bias leads to genome size reduction in hermaphroditic species, a pattern consistent with differences in genome sizes in the genus Caenorhabditis. These results suggest that insertions and deletions may affect chromosome segregation patterns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, John -- Chen, Pei-Jiun -- Wang, George J -- Keller, Laurent -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jul 16;329(5989):293. doi: 10.1126/science.1190130.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, University of Lausanne, CH-1015 Lausanne, Switzerland. John.Wang@unil.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647459" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*genetics/physiology ; Chromosome Deletion ; *Chromosome Segregation ; Chromosomes/*genetics ; Disorders of Sex Development ; Female ; *Genome ; INDEL Mutation ; Male ; *Meiosis ; Mutagenesis, Insertional ; Transgenes ; X Chromosome/genetics
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  • 171
    Publication Date: 2010-07-31
    Description: Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161413/" 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/PMC3161413/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buckholtz, Joshua W -- Treadway, Michael T -- Cowan, Ronald L -- Woodward, Neil D -- Li, Rui -- Ansari, M Sib -- Baldwin, Ronald M -- Schwartzman, Ashley N -- Shelby, Evan S -- Smith, Clarence E -- Kessler, Robert M -- Zald, David H -- R01 DA019670/DA/NIDA NIH HHS/ -- R01 DA019670-04/DA/NIDA NIH HHS/ -- R01DA019670-04/DA/NIDA NIH HHS/ -- T32 MH018921/MH/NIMH NIH HHS/ -- T32 MH018921-22/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):532. doi: 10.1126/science.1185778.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA. joshua.buckholtz@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671181" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Amphetamine-Related Disorders/etiology/metabolism ; Autoreceptors/metabolism ; Benzamides/metabolism ; Corpus Striatum/*metabolism ; Dextroamphetamine/*administration & dosage ; Dopamine/*metabolism ; Female ; Humans ; Impulsive Behavior/*metabolism ; Ligands ; Male ; Positron-Emission Tomography ; Pyrrolidines/metabolism ; Receptors, Dopamine D2/metabolism ; Receptors, Dopamine D3/*metabolism ; Signal Transduction ; Substantia Nigra/metabolism ; Tegmentum Mesencephali/*metabolism ; Ventral Tegmental Area/metabolism ; Young Adult
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  • 172
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):260-2. doi: 10.1126/science.327.5963.260.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075226" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Genes, Insect ; *Genome, Insect ; Insects/parasitology ; Lepidoptera/parasitology ; Male ; Pest Control, Biological ; Research ; Sequence Analysis, DNA ; Wasps/classification/*genetics/microbiology/physiology
    Print ISSN: 0036-8075
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  • 173
    Publication Date: 2010-06-26
    Description: Touch is both the first sense to develop and a critical means of information acquisition and environmental manipulation. Physical touch experiences may create an ontological scaffold for the development of intrapersonal and interpersonal conceptual and metaphorical knowledge, as well as a springboard for the application of this knowledge. In six experiments, holding heavy or light clipboards, solving rough or smooth puzzles, and touching hard or soft objects nonconsciously influenced impressions and decisions formed about unrelated people and situations. Among other effects, heavy objects made job candidates appear more important, rough objects made social interactions appear more difficult, and hard objects increased rigidity in negotiations. Basic tactile sensations are thus shown to influence higher social cognitive processing in dimension-specific and metaphor-specific ways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005631/" 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/PMC3005631/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ackerman, Joshua M -- Nocera, Christopher C -- Bargh, John A -- MH60767/MH/NIMH NIH HHS/ -- R01 MH060767-10/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2010 Jun 25;328(5986):1712-5. doi: 10.1126/science.1189993.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sloan School of Management, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E62, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576894" target="_blank"〉PubMed〈/a〉
    Keywords: Cognition ; Cues ; *Decision Making ; Female ; Games, Experimental ; Humans ; *Judgment ; Male ; Metaphor ; *Social Perception ; *Touch ; Touch Perception ; Young Adult
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  • 174
    Publication Date: 2010-05-15
    Description: Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simonson, Tatum S -- Yang, Yingzhong -- Huff, Chad D -- Yun, Haixia -- Qin, Ga -- Witherspoon, David J -- Bai, Zhenzhong -- Lorenzo, Felipe R -- Xing, Jinchuan -- Jorde, Lynn B -- Prchal, Josef T -- Ge, RiLi -- 1P01CA108671-01A2/CA/NCI NIH HHS/ -- DK069513/DK/NIDDK NIH HHS/ -- GM059290/GM/NIGMS NIH HHS/ -- HL50077/HL/NHLBI NIH HHS/ -- R00 HG005846/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):72-5. doi: 10.1126/science.1189406. Epub 2010 May 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466884" target="_blank"〉PubMed〈/a〉
    Keywords: *Acclimatization ; *Altitude ; Asian Continental Ancestry Group/genetics ; Ethnic Groups/genetics ; Female ; Genetic Association Studies ; Genetic Variation ; Genome, Human ; Haplotypes ; Hemoglobins/*analysis ; Humans ; Hypoxia-Inducible Factor 1/metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; Linear Models ; Male ; *Oxygen ; PPAR alpha/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Procollagen-Proline Dioxygenase/*genetics ; *Selection, Genetic ; Signal Transduction ; Tibet
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  • 175
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):22. doi: 10.1126/science.330.6000.22.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929781" target="_blank"〉PubMed〈/a〉
    Keywords: *Cooperative Behavior ; *Emotional Intelligence ; Female ; *Group Processes ; Humans ; *Intelligence ; Male
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  • 176
    Publication Date: 2010-05-01
    Description: Mirror movements are involuntary contralateral movements that mirror voluntary ones and are often associated with defects in midline crossing of the developing central nervous system. We studied two large families, one French Canadian and one Iranian, in which isolated congenital mirror movements were inherited as an autosomal dominant trait. We found that affected individuals carried protein-truncating mutations in DCC (deleted in colorectal carcinoma), a gene on chromosome 18q21.2 that encodes a receptor for netrin-1, a diffusible protein that helps guide axon growth across the midline. Functional analysis of the mutant DCC protein from the French Canadian family revealed a defect in netrin-1 binding. Thus, DCC has an important role in lateralization of the human nervous system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Srour, Myriam -- Riviere, Jean-Baptiste -- Pham, Jessica M T -- Dube, Marie-Pierre -- Girard, Simon -- Morin, Steves -- Dion, Patrick A -- Asselin, Geraldine -- Rochefort, Daniel -- Hince, Pascale -- Diab, Sabrina -- Sharafaddinzadeh, Naser -- Chouinard, Sylvain -- Theoret, Hugo -- Charron, Frederic -- Rouleau, Guy A -- New York, N.Y. -- Science. 2010 Apr 30;328(5978):592. doi: 10.1126/science.1186463.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Excellence in Neuromics, Universite de Montreal, Montreal, QC H2L 2W5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20431009" target="_blank"〉PubMed〈/a〉
    Keywords: Axons/physiology ; Codon, Terminator ; Dyskinesias/*congenital/*genetics ; Female ; *Frameshift Mutation ; Functional Laterality ; *Genes, DCC ; Genes, Dominant ; Genome-Wide Association Study ; Haplotypes ; Humans ; Male ; Mutant Proteins/chemistry/metabolism ; Nerve Growth Factors/metabolism ; Nervous System/growth & development ; Pedigree ; Protein Binding ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Tumor Suppressor Proteins/chemistry/genetics/*metabolism
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  • 177
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2010 Jul 16;329(5989):262. doi: 10.1126/science.329.5989.262.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647430" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/analysis/*genetics ; *DNA Fingerprinting ; Databases, Nucleic Acid ; *Family ; *Homicide ; Humans ; Male ; Microsatellite Repeats
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  • 178
    Publication Date: 2010-04-17
    Description: The anterior prefrontal cortex (APC) confers on humans the ability to simultaneously pursue several goals. How does the brain's motivational system, including the medial frontal cortex (MFC), drive the pursuit of concurrent goals? Using brain imaging, we observed that the left and right MFC, which jointly drive single-task performance according to expected rewards, divide under dual-task conditions: While the left MFC encodes the rewards driving one task, the right MFC concurrently encodes those driving the other task. The same dichotomy was observed in the lateral frontal cortex, whereas the APC combined the rewards driving both tasks. The two frontal lobes thus divide for representing simultaneously two concurrent goals coordinated by the APC. The human frontal function seems limited to driving the pursuit of two concurrent goals simultaneously.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Charron, Sylvain -- Koechlin, Etienne -- New York, N.Y. -- Science. 2010 Apr 16;328(5976):360-3. doi: 10.1126/science.1183614.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Sante et de la Recherche Medicale, Paris F-75654 Cedex 13, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20395509" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain Mapping ; Cues ; Female ; Frontal Lobe/*physiology ; *Goals ; Humans ; Magnetic Resonance Imaging ; Male ; Prefrontal Cortex/*physiology ; Psychomotor Performance ; *Reward ; Task Performance and Analysis ; Ventral Tegmental Area/physiology ; Young Adult
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  • 179
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1343. doi: 10.1126/science.328.5984.1343-a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20538926" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression/*drug effects ; *Altruism ; Game Theory ; Humans ; Interpersonal Relations ; Male ; Oxytocin/*pharmacology/physiology
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  • 180
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-10
    Description: Most firefly species (Coleoptera: Lampyridae) use bioluminescent flashes for signaling. In some species, the flashing between males occurs rhythmically and repeatedly (synchronically) with millisecond precision. We studied synchrony's behavioral role in the North American firefly, Photinus carolinus. We placed a female in a virtual environment containing artificial males that flashed at varying degrees of synchrony. Females responded to an average of 82% of synchronous flashes compared with as few as 3% of asynchronous flashes. We conclude that one function of flash synchrony is to facilitate a female's ability to recognize her conspecific male's flashing by eliminating potential visual clutter from other flashing males.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moiseff, Andrew -- Copeland, Jonathan -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):181. doi: 10.1126/science.1190421.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA. Andrew.Moiseff@UConn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20616271" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Communication ; Animals ; Behavior, Animal ; Female ; Fireflies/*physiology ; *Light ; Male ; *Periodicity ; Species Specificity ; Vision, Ocular/physiology
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  • 181
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hvistendahl, Mara -- New York, N.Y. -- Science. 2010 Sep 17;329(5998):1458-61. doi: 10.1126/science.329.5998.1458.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20847244" target="_blank"〉PubMed〈/a〉
    Keywords: Age Distribution ; Birth Rate ; Child ; China ; *Family Characteristics ; *Family Planning Policy ; Female ; Humans ; Male ; Only Child ; *Population Control ; Population Dynamics ; *Population Growth ; Sex Ratio
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  • 182
    Publication Date: 2010-07-03
    Description: Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711608/" 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/PMC3711608/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yi, Xin -- Liang, Yu -- Huerta-Sanchez, Emilia -- Jin, Xin -- Cuo, Zha Xi Ping -- Pool, John E -- Xu, Xun -- Jiang, Hui -- Vinckenbosch, Nicolas -- Korneliussen, Thorfinn Sand -- Zheng, Hancheng -- Liu, Tao -- He, Weiming -- Li, Kui -- Luo, Ruibang -- Nie, Xifang -- Wu, Honglong -- Zhao, Meiru -- Cao, Hongzhi -- Zou, Jing -- Shan, Ying -- Li, Shuzheng -- Yang, Qi -- Asan -- Ni, Peixiang -- Tian, Geng -- Xu, Junming -- Liu, Xiao -- Jiang, Tao -- Wu, Renhua -- Zhou, Guangyu -- Tang, Meifang -- Qin, Junjie -- Wang, Tong -- Feng, Shuijian -- Li, Guohong -- Huasang -- Luosang, Jiangbai -- Wang, Wei -- Chen, Fang -- Wang, Yading -- Zheng, Xiaoguang -- Li, Zhuo -- Bianba, Zhuoma -- Yang, Ge -- Wang, Xinping -- Tang, Shuhui -- Gao, Guoyi -- Chen, Yong -- Luo, Zhen -- Gusang, Lamu -- Cao, Zheng -- Zhang, Qinghui -- Ouyang, Weihan -- Ren, Xiaoli -- Liang, Huiqing -- Zheng, Huisong -- Huang, Yebo -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Li, Yingrui -- Zhang, Yong -- Zhang, Xiuqing -- Li, Ruiqiang -- Li, Songgang -- Yang, Huanming -- Nielsen, Rasmus -- Wang, Jun -- Wang, Jian -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 MH084695/MH/NIMH NIH HHS/ -- R01HG003229/HG/NHGRI NIH HHS/ -- R01MHG084695/PHS HHS/ -- New York, N.Y. -- Science. 2010 Jul 2;329(5987):75-8. doi: 10.1126/science.1190371.〈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/20595611" target="_blank"〉PubMed〈/a〉
    Keywords: Acclimatization/*genetics ; *Altitude ; Asian Continental Ancestry Group/genetics ; Basic Helix-Loop-Helix Transcription Factors/*genetics/physiology ; Bayes Theorem ; China ; Erythrocyte Count ; Ethnic Groups/genetics ; *Exons ; Female ; Gene Frequency ; Genetic Association Studies ; *Genome, Human ; Hemoglobins/analysis ; Humans ; Male ; Oxygen/blood ; Polymorphism, Single Nucleotide ; *Selection, Genetic ; Sequence Analysis, DNA ; Tibet
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  • 183
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enserink, Martin -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1460-1. doi: 10.1126/science.330.6010.1460.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148356" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*microbiology/*virology ; Animals ; Dengue/prevention & control/*transmission ; Dengue Virus/*physiology ; Female ; Humans ; Insect Vectors/*microbiology/virology ; Male ; Queensland ; Wolbachia/*physiology
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  • 184
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, Andrew -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1472-3. doi: 10.1126/science.330.6010.1472-b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148366" target="_blank"〉PubMed〈/a〉
    Keywords: *Archaeology ; Chromosomes, Human, Y/*genetics ; Emigration and Immigration/*history ; *Genetic Markers ; History, Ancient ; Humans ; Male ; Mediterranean Region ; Middle East
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  • 185
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-01-09
    Description: In cases where uninvolved bystanders pay to punish defectors, this behavior has typically been interpreted in terms of group-level rather than individual-level benefits. Male cleaner fish, Labroides dimidiatus, punish their female partner if she cheats while inspecting model clients. Punishment promotes female cooperation and thereby yields direct foraging benefits to the male. Thus, third-party punishment can evolve via self-serving tendencies in a nonhuman species, and this finding may shed light on the evolutionary dynamics of more complex behavior in other animal species, including humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raihani, Nichola J -- Grutter, Alexandra S -- Bshary, Redouan -- New York, N.Y. -- Science. 2010 Jan 8;327(5962):171. doi: 10.1126/science.1183068.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Zoology, Zoological Society of London, Regent's Park, London NW1 4RY, UK. nichola.raihani@ioz.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20056883" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Biological Evolution ; *Cooperative Behavior ; Decapoda (Crustacea) ; Feeding Behavior ; Female ; Fishes ; Male ; *Perciformes ; *Punishment
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  • 186
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-07-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):378. doi: 10.1126/science.329.5990.378.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20651127" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; China ; *Conservation of Natural Resources ; *Ecosystem ; *Endangered Species ; Extinction, Biological ; Female ; Fisheries ; *Fishes ; Human Activities ; Humans ; Male ; Population Dynamics ; *Porpoises ; *Rivers
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  • 187
    Publication Date: 2010-08-28
    Description: In everyday life, many people believe that two heads are better than one. Our ability to solve problems together appears to be fundamental to the current dominance and future survival of the human species. But are two heads really better than one? We addressed this question in the context of a collective low-level perceptual decision-making task. For two observers of nearly equal visual sensitivity, two heads were definitely better than one, provided they were given the opportunity to communicate freely, even in the absence of any feedback about decision outcomes. But for observers with very different visual sensitivities, two heads were actually worse than the better one. These seemingly discrepant patterns of group behavior can be explained by a model in which two heads are Bayes optimal under the assumption that individuals accurately communicate their level of confidence on every trial.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371582/" 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/PMC3371582/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bahrami, Bahador -- Olsen, Karsten -- Latham, Peter E -- Roepstorff, Andreas -- Rees, Geraint -- Frith, Chris D -- 082334/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1081-5. doi: 10.1126/science.1185718.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College London Institute of Cognitive Neuroscience, University College London, Alexandra House, 17 Queen Square, London WC1N 3AR, UK. bbahrami@gmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798320" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Bayes Theorem ; *Communication ; *Cooperative Behavior ; *Decision Making ; Feedback, Psychological ; *Group Processes ; Humans ; Male ; Models, Psychological ; Probability ; Psychometrics ; Uncertainty ; *Visual Perception
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  • 188
    Publication Date: 2010-12-15
    Description: The consumption of a food typically leads to a decrease in its subsequent intake through habituation--a decrease in one's responsiveness to the food and motivation to obtain it. We demonstrated that habituation to a food item can occur even when its consumption is merely imagined. Five experiments showed that people who repeatedly imagined eating a food (such as cheese) many times subsequently consumed less of the imagined food than did people who repeatedly imagined eating that food fewer times, imagined eating a different food (such as candy), or did not imagine eating a food. They did so because they desired to eat it less, not because they considered it less palatable. These results suggest that mental representation alone can engender habituation to a stimulus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morewedge, Carey K -- Huh, Young Eun -- Vosgerau, Joachim -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1530-3. doi: 10.1126/science.1195701.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Social and Decision Sciences, Porter Hall 208, Carnegie Mellon University, Pittsburgh, PA, USA. morewedge@cmu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148388" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Analysis of Variance ; Appetite ; Candy ; Cheese ; *Eating ; *Feeding Behavior ; Female ; Food Preferences ; *Habituation, Psychophysiologic ; Humans ; *Imagination ; Male ; Motivation ; Reinforcement (Psychology) ; Young Adult
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  • 189
    Publication Date: 2010-08-28
    Description: Somatic loss of wild-type alleles can produce disease traits such as neoplasia. Conversely, somatic loss of disease-causing mutations can revert phenotypes; however, these events are infrequently observed. Here we show that ichthyosis with confetti, a severe, sporadic skin disease in humans, is associated with thousands of revertant clones of normal skin that arise from loss of heterozygosity on chromosome 17q via mitotic recombination. This allowed us to map and identify disease-causing mutations in the gene encoding keratin 10 (KRT10); all result in frameshifts into the same alternative reading frame, producing an arginine-rich C-terminal peptide that redirects keratin 10 from the cytokeratin filament network to the nucleolus. The high frequency of somatic reversion in ichthyosis with confetti suggests that revertant stem cell clones are under strong positive selection and/or that the rate of mitotic recombination is elevated in individuals with this disorder.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085938/" 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/PMC3085938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choate, Keith A -- Lu, Yin -- Zhou, Jing -- Choi, Murim -- Elias, Peter M -- Farhi, Anita -- Nelson-Williams, Carol -- Crumrine, Debra -- Williams, Mary L -- Nopper, Amy J -- Bree, Alanna -- Milstone, Leonard M -- Lifton, Richard P -- K08 AR056305/AR/NIAMS NIH HHS/ -- K08 AR056305-01/AR/NIAMS NIH HHS/ -- K08 AR056305-02/AR/NIAMS NIH HHS/ -- K08 AR056305-03/AR/NIAMS NIH HHS/ -- K08 AR056305-04/AR/NIAMS NIH HHS/ -- T32 AR007016/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):94-7. doi: 10.1126/science.1192280. Epub 2010 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798280" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Nucleolus/metabolism ; Chromosome Mapping ; Chromosomes, Human, Pair 17/*genetics ; Female ; *Frameshift Mutation ; Humans ; Ichthyosiform Erythroderma, Congenital/*genetics/pathology ; Intermediate Filaments/metabolism/ultrastructure ; Keratin-10/chemistry/*genetics/metabolism ; Keratins/metabolism ; Loss of Heterozygosity ; Male ; *Mitosis ; Molecular Sequence Data ; Mosaicism ; Mutant Proteins/chemistry/genetics/metabolism ; *Recombination, Genetic ; Selection, Genetic ; Skin/pathology
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  • 190
    Publication Date: 2010-07-31
    Description: Gain-of-function mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial as well as sporadic Parkinson's disease characterized by age-dependent degeneration of dopaminergic neurons. The molecular mechanism of LRRK2 action is not known. Here we show that LRRK2 interacts with the microRNA (miRNA) pathway to regulate protein synthesis. Drosophila e2f1 and dp messenger RNAs are translationally repressed by let-7 and miR-184*, respectively. Pathogenic LRRK2 antagonizes these miRNAs, leading to the overproduction of E2F1/DP, previously implicated in cell cycle and survival control and shown here to be critical for LRRK2 pathogenesis. Genetic deletion of let-7, antagomir-mediated blockage of let-7 and miR-184* action, transgenic expression of dp target protector, or replacement of endogenous dp with a dp transgene non-responsive to let-7 each had toxic effects similar to those of pathogenic LRRK2. Conversely, increasing the level of let-7 or miR-184* attenuated pathogenic LRRK2 effects. LRRK2 associated with Drosophila Argonaute-1 (dAgo1) or human Argonaute-2 (hAgo2) of the RNA-induced silencing complex (RISC). In aged fly brain, dAgo1 protein level was negatively regulated by LRRK2. Further, pathogenic LRRK2 promoted the association of phospho-4E-BP1 with hAgo2. Our results implicate deregulated synthesis of E2F1/DP caused by the miRNA pathway impairment as a key event in LRRK2 pathogenesis and suggest novel miRNA-based therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049892/" 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/PMC3049892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gehrke, Stephan -- Imai, Yuzuru -- Sokol, Nicholas -- Lu, Bingwei -- R01 AR054926/AR/NIAMS NIH HHS/ -- R01 AR054926-01A2/AR/NIAMS NIH HHS/ -- R01 MH080378/MH/NIMH NIH HHS/ -- R01 MH080378-01A2/MH/NIMH NIH HHS/ -- R01AR054926/AR/NIAMS NIH HHS/ -- R01MH080378/MH/NIMH NIH HHS/ -- R21 NS056878/NS/NINDS NIH HHS/ -- R21 NS056878-01A1/NS/NINDS NIH HHS/ -- R21NS056878/NS/NINDS NIH HHS/ -- England -- Nature. 2010 Jul 29;466(7306):637-41. doi: 10.1038/nature09191.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. sgehrke@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671708" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Cell Line ; Dopamine/metabolism ; *Down-Regulation ; Drosophila Proteins/biosynthesis/genetics/metabolism ; Drosophila melanogaster ; E2F1 Transcription Factor/biosynthesis/genetics/metabolism ; Eukaryotic Initiation Factor-2/metabolism ; Eukaryotic Initiation Factors/biosynthesis/metabolism ; Female ; Humans ; Male ; MicroRNAs/antagonists & inhibitors/*genetics/*metabolism ; Neurons/cytology/metabolism ; Parkinson Disease/etiology/genetics/metabolism ; Protein Binding ; *Protein Biosynthesis ; Protein-Serine-Threonine Kinases/*genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; RNA-Induced Silencing Complex/antagonists & inhibitors/chemistry/metabolism ; Trans-Activators/biosynthesis/genetics/metabolism ; Up-Regulation
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  • 191
    Publication Date: 2010-02-09
    Description: Induced pluripotent stem (iPS) cells can be obtained by the introduction of defined factors into somatic cells. The combination of Oct4 (also known as Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement for generating iPS cells from mouse embryonic fibroblasts. These cells are thought to resemble embryonic stem cells (ESCs) on the basis of global gene expression analyses; however, few studies have tested the ability and efficiency of iPS cells to contribute to chimaerism, colonization of germ tissues, and most importantly, germ-line transmission and live birth from iPS cells produced by tetraploid complementation. Using genomic analyses of ESC genes that have roles in pluripotency and fusion-mediated somatic cell reprogramming, here we show that the transcription factor Tbx3 significantly improves the quality of iPS cells. iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell contribution to the gonads and germ-line transmission frequency. However, global gene expression profiling could not distinguish between OSK and OSKT iPS cells. Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding sites in ESCs suggests that Tbx3 regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic qualitative differences between iPS cells generated by different methods, and highlights the need to rigorously characterize iPS cells beyond in vitro studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901797/" 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/PMC2901797/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Jianyong -- Yuan, Ping -- Yang, Henry -- Zhang, Jinqiu -- Soh, Boon Seng -- Li, Pin -- Lim, Siew Lan -- Cao, Suying -- Tay, Junliang -- Orlov, Yuriy L -- Lufkin, Thomas -- Ng, Huck-Hui -- Tam, Wai-Leong -- Lim, Bing -- AI54973/AI/NIAID NIH HHS/ -- DK047636/DK/NIDDK NIH HHS/ -- R01 AI054973-05/AI/NIAID NIH HHS/ -- R01 DK047636-08/DK/NIDDK NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1096-100. doi: 10.1038/nature08735. Epub 2010 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell and Developmental Biology, Genome Institute of Singapore, 138672, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20139965" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Fusion ; Cellular Reprogramming ; Chimera/embryology/*metabolism ; Chromatin Immunoprecipitation ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling ; Gene Expression Regulation/genetics ; Germ Cells/*cytology/*metabolism ; Gonads/*cytology ; Homeodomain Proteins/metabolism ; Induced Pluripotent Stem Cells/*cytology/*metabolism ; Kruppel-Like Transcription Factors/genetics/metabolism ; Male ; Mice ; Mice, Transgenic ; Octamer Transcription Factor-3/genetics/metabolism ; Regulatory Sequences, Nucleic Acid ; SOXB1 Transcription Factors/genetics/metabolism ; Smad1 Protein/metabolism ; T-Box Domain Proteins/genetics/*metabolism ; Transcription, Genetic/genetics ; Transduction, Genetic
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  • 192
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbott, Alison -- England -- Nature. 2010 Oct 7;467(7316):641-2. doi: 10.1038/467641a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20930811" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; *Fertilization in Vitro/ethics/history ; Great Britain ; History, 20th Century ; History, 21st Century ; Humans ; Male ; *Nobel Prize
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  • 193
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rennison, Andrew -- England -- Nature. 2010 May 13;465(7295):157. doi: 10.1038/465157c.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463716" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/analysis/genetics ; Forensic Genetics/*legislation & jurisprudence/methods/*standards ; Great Britain ; Humans ; Male ; Reproducibility of Results ; Sequence Analysis, DNA/*standards ; *Specimen Handling ; Templates, Genetic
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 194
    Publication Date: 2010-08-24
    Description: The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129007/" 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/PMC3129007/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bilguvar, Kaya -- Ozturk, Ali Kemal -- Louvi, Angeliki -- Kwan, Kenneth Y -- Choi, Murim -- Tatli, Burak -- Yalnizoglu, Dilek -- Tuysuz, Beyhan -- Caglayan, Ahmet Okay -- Gokben, Sarenur -- Kaymakcalan, Hande -- Barak, Tanyeri -- Bakircioglu, Mehmet -- Yasuno, Katsuhito -- Ho, Winson -- Sanders, Stephan -- Zhu, Ying -- Yilmaz, Sanem -- Dincer, Alp -- Johnson, Michele H -- Bronen, Richard A -- Kocer, Naci -- Per, Huseyin -- Mane, Shrikant -- Pamir, Mehmet Necmettin -- Yalcinkaya, Cengiz -- Kumandas, Sefer -- Topcu, Meral -- Ozmen, Meral -- Sestan, Nenad -- Lifton, Richard P -- State, Matthew W -- Gunel, Murat -- RC2 NS070477/NS/NINDS NIH HHS/ -- RC2 NS070477-01/NS/NINDS NIH HHS/ -- U01 MH081896/MH/NIMH NIH HHS/ -- U24 NS051869-02S1/NS/NINDS NIH HHS/ -- UL1 RR024139NIH/RR/NCRR NIH HHS/ -- UO1MH081896/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Sep 9;467(7312):207-10. doi: 10.1038/nature09327. Epub 2010 Aug 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20729831" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Brain/*abnormalities/growth & development/pathology ; Brain Diseases/*genetics/pathology ; DNA Mutational Analysis/*methods ; Female ; Genes, Recessive ; Humans ; Male ; Mice ; Microcephaly/genetics/pathology ; Molecular Sequence Data ; Mutation ; Nerve Tissue Proteins/*genetics/metabolism ; Pedigree
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 195
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    Nature Publishing Group (NPG)
    Publication Date: 2010-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spinney, Laura -- England -- Nature. 2010 Mar 18;464(7287):344-6. doi: 10.1038/464344a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20237537" target="_blank"〉PubMed〈/a〉
    Keywords: Bias (Epidemiology) ; *Dermatoglyphics ; False Positive Reactions ; Forensic Sciences/*methods/standards ; Humans ; Male ; Reproducibility of Results ; Research Design ; Spain ; Terrorism/legislation & jurisprudence
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 196
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    Nature Publishing Group (NPG)
    Publication Date: 2010-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2010 Jan 14;463(7278):149. doi: 10.1038/463149a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075893" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes, Human, Y/genetics ; *Evolution, Molecular ; Female ; Humans ; Male ; Pan troglodytes/*genetics ; Synteny ; Y Chromosome/*genetics
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  • 197
    Publication Date: 2010-06-11
    Description: Down's syndrome (DS) is a genetic disorder caused by full or partial trisomy of human chromosome 21 and presents with many clinical phenotypes including a reduced incidence of solid tumours. Recent work with the Ts65Dn model of DS, which has orthologues of about 50% of the genes on chromosome 21 (Hsa21), has indicated that three copies of the ETS2 (ref. 3) or DS candidate region 1 (DSCR1) genes (a previously known suppressor of angiogenesis) is sufficient to inhibit tumour growth. Here we use the Tc1 transchromosomic mouse model of DS to dissect the contribution of extra copies of genes on Hsa21 to tumour angiogenesis. This mouse expresses roughly 81% of Hsa21 genes but not the human DSCR1 region. We transplanted B16F0 and Lewis lung carcinoma tumour cells into Tc1 mice and showed that growth of these tumours was substantially reduced compared with wild-type littermate controls. Furthermore, tumour angiogenesis was significantly repressed in Tc1 mice. In particular, in vitro and in vivo angiogenic responses to vascular endothelial growth factor (VEGF) were inhibited. Examination of the genes on the segment of Hsa21 in Tc1 mice identified putative anti-angiogenic genes (ADAMTS1and ERG) and novel endothelial cell-specific genes, never previously shown to be involved in angiogenesis (JAM-B and PTTG1IP), that, when overexpressed, are responsible for inhibiting angiogenic responses to VEGF. Three copies of these genes within the stromal compartment reduced tumour angiogenesis, explaining the reduced tumour growth in DS. Furthermore, we expect that, in addition to the candidate genes that we show to be involved in the repression of angiogenesis, the Tc1 mouse model of DS will permit the identification of other endothelium-specific anti-angiogenic targets relevant to a broad spectrum of cancer patients.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479956/" 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/PMC3479956/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reynolds, Louise E -- Watson, Alan R -- Baker, Marianne -- Jones, Tania A -- D'Amico, Gabriela -- Robinson, Stephen D -- Joffre, Carine -- Garrido-Urbani, Sarah -- Rodriguez-Manzaneque, Juan Carlos -- Martino-Echarri, Estefania -- Aurrand-Lions, Michel -- Sheer, Denise -- Dagna-Bricarelli, Franca -- Nizetic, Dean -- McCabe, Christopher J -- Turnell, Andrew S -- Kermorgant, Stephanie -- Imhof, Beat A -- Adams, Ralf -- Fisher, Elizabeth M C -- Tybulewicz, Victor L J -- Hart, Ian R -- Hodivala-Dilke, Kairbaan M -- 080174/Wellcome Trust/United Kingdom -- 12007/Cancer Research UK/United Kingdom -- A12007/Cancer Research UK/United Kingdom -- A3585/Cancer Research UK/United Kingdom -- G0501003/Medical Research Council/United Kingdom -- G0501003(75694)/Medical Research Council/United Kingdom -- G0601056/Medical Research Council/United Kingdom -- G0901609/Medical Research Council/United Kingdom -- MC_U117527252/Medical Research Council/United Kingdom -- U.1175.02.001.00001(60485)/Medical Research Council/United Kingdom -- England -- Nature. 2010 Jun 10;465(7299):813-7. doi: 10.1038/nature09106.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Adhesion and Angiogenesis Laboratory, Barts Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. l.reynolds@qmul.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535211" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins/genetics/metabolism ; Animals ; Carcinoma, Lewis Lung/*blood supply/complications/genetics/pathology ; Carrier Proteins/genetics/metabolism ; Cell Adhesion Molecules/antagonists & inhibitors/genetics/metabolism ; Chromosomes, Mammalian/genetics ; *Disease Models, Animal ; Down Syndrome/complications/*genetics/physiopathology ; Female ; Gene Dosage/*genetics ; Humans ; Immunoglobulins/genetics/metabolism ; Male ; Melanoma, Experimental/*blood supply/complications/genetics/pathology ; Mice ; Neoplasm Transplantation ; Neovascularization, Pathologic/*genetics/pathology ; Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Protein c-ets-2/genetics/metabolism ; Transcription Factors ; Trisomy/genetics ; Vascular Endothelial Growth Factor A/antagonists & ; inhibitors/metabolism/pharmacology ; Vascular Endothelial Growth Factor Receptor-2/metabolism
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  • 198
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blakemore, Colin -- England -- Nature. 2010 Jul 1;466(7302):45. doi: 10.1038/466045a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20596011" target="_blank"〉PubMed〈/a〉
    Keywords: Great Britain ; History, 20th Century ; Humans ; Illusions/physiology/psychology ; Male ; Middle Aged ; Neurophysiology/*history ; Perception/physiology ; Psychology/*history
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  • 199
    Publication Date: 2010-07-03
    Description: Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P 〈or= 5 x 10(-7)). Here we show an association with genomic regions containing several genes controlling the activation and proliferation of regulatory T cells (T(reg) cells), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), interleukin (IL)-2/IL-21, IL-2 receptor A (IL-2RA; CD25) and Eos (also known as Ikaros family zinc finger 4; IKZF4), as well as the human leukocyte antigen (HLA) region. We also find association evidence for regions containing genes expressed in the hair follicle itself (PRDX5 and STX17). A region of strong association resides within the ULBP (cytomegalovirus UL16-binding protein) gene cluster on chromosome 6q25.1, encoding activating ligands of the natural killer cell receptor NKG2D that have not previously been implicated in an autoimmune disease. By probing the role of ULBP3 in disease pathogenesis, we also show that its expression in lesional scalp from patients with AA is markedly upregulated in the hair follicle dermal sheath during active disease. This study provides evidence for the involvement of both innate and acquired immunity in the pathogenesis of AA. We have defined the genetic underpinnings of AA, placing it within the context of shared pathways among autoimmune diseases, and implicating a novel disease mechanism, the upregulation of ULBP ligands, in triggering autoimmunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921172/" 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/PMC2921172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Petukhova, Lynn -- Duvic, Madeleine -- Hordinsky, Maria -- Norris, David -- Price, Vera -- Shimomura, Yutaka -- Kim, Hyunmi -- Singh, Pallavi -- Lee, Annette -- Chen, Wei V -- Meyer, Katja C -- Paus, Ralf -- Jahoda, Colin A B -- Amos, Christopher I -- Gregersen, Peter K -- Christiano, Angela M -- P30CA016772/CA/NCI NIH HHS/ -- R01 AR056016/AR/NIAMS NIH HHS/ -- R01 AR056016-03/AR/NIAMS NIH HHS/ -- R01AR44422/AR/NIAMS NIH HHS/ -- R01AR52579/AR/NIAMS NIH HHS/ -- R01AR56016/AR/NIAMS NIH HHS/ -- R01CA133996/CA/NCI NIH HHS/ -- England -- Nature. 2010 Jul 1;466(7302):113-7. doi: 10.1038/nature09114.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Dermatology, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20596022" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity/*genetics/immunology ; Adult ; Aged ; Alleles ; Alopecia Areata/*genetics/immunology ; Antigens, CD/genetics ; Autoimmune Diseases/*genetics/immunology ; CTLA-4 Antigen ; Case-Control Studies ; Female ; GPI-Linked Proteins ; *Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Hair Follicle/cytology/immunology/metabolism ; Humans ; Ikaros Transcription Factor/genetics ; Immunity, Innate/*genetics/immunology ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Interleukin-2 Receptor alpha Subunit/genetics ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; Peroxiredoxins/genetics ; Polymorphism, Single Nucleotide/genetics ; Qa-SNARE Proteins/genetics ; T-Lymphocytes, Regulatory/cytology/immunology
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 200
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    Nature Publishing Group (NPG)
    Publication Date: 2010-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Handyside, Alan -- England -- Nature. 2010 Apr 15;464(7291):978-9. doi: 10.1038/464978a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉London Bridge Fertility, Gynaecology and Genetics Centre, London SE1 9RY, UK. ahandyside@thebridgecentre.co.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393539" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Genetic Testing/ethics/trends ; Humans ; Male ; *Parents/psychology ; Phenotype ; Preimplantation Diagnosis/*ethics/trends ; Reproductive Techniques, Assisted/ethics/trends
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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