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  • Mice  (192)
  • Male  (145)
  • American Association for the Advancement of Science (AAAS)  (304)
  • 2010-2014  (304)
  • 2010  (304)
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  • 2010-2014  (304)
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  • 1
    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-12-15
    Description: Insulin-like growth factor 1 (IGF-1) induces skeletal muscle maturation and enlargement (hypertrophy). These responses require protein synthesis and myofibril formation (myofibrillogenesis). However, the signaling mechanisms of myofibrillogenesis remain obscure. We found that IGF-1-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-WASP at the Z bands of myofibrils by interfering with glycogen synthase kinase-3beta in mice. Although N-WASP is known to be an activator of the Arp2/3 complex to form branched actin filaments, the nebulin-N-WASP complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-WASP was required for IGF-1-induced muscle hypertrophy. These findings present the mechanisms of IGF-1-induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takano, Kazunori -- Watanabe-Takano, Haruko -- Suetsugu, Shiro -- Kurita, Souichi -- Tsujita, Kazuya -- Kimura, Sumiko -- Karatsu, Takashi -- Takenawa, Tadaomi -- Endo, Takeshi -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1536-40. doi: 10.1126/science.1197767.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Graduate School of Science, Chiba University, 1-33 Yayoicho, Inageku, Chiba 263-8522, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148390" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Animals ; COS Cells ; Cercopithecus aethiops ; Hypertrophy ; Insulin-Like Growth Factor I/*metabolism ; Mice ; Mice, Inbred ICR ; *Muscle Development ; Muscle Proteins/chemistry/*metabolism ; Muscle, Skeletal/metabolism/pathology ; Myofibrils/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Sarcomeres/*metabolism ; Signal Transduction ; Wiskott-Aldrich Syndrome Protein, Neuronal/chemistry/*metabolism ; src Homology Domains
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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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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  • 4
    Publication Date: 2010-01-02
    Description: Meiotic recombination events cluster into narrow segments of the genome, defined as hotspots. Here, we demonstrate that a major player for hotspot specification is the Prdm9 gene. First, two mouse strains that differ in hotspot usage are polymorphic for the zinc finger DNA binding array of PRDM9. Second, the human consensus PRDM9 allele is predicted to recognize the 13-mer motif enriched at human hotspots; this DNA binding specificity is verified by in vitro studies. Third, allelic variants of PRDM9 zinc fingers are significantly associated with variability in genome-wide hotspot usage among humans. Our results provide a molecular basis for the distribution of meiotic recombination in mammals, in which the binding of PRDM9 to specific DNA sequences targets the initiation of recombination at specific locations in the genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295902/" 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/PMC4295902/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baudat, F -- Buard, J -- Grey, C -- Fledel-Alon, A -- Ober, C -- Przeworski, M -- Coop, G -- de Massy, B -- 03S1/PHS HHS/ -- GM83098/GM/NIGMS NIH HHS/ -- HD21244/HD/NICHD NIH HHS/ -- HL085197/HL/NHLBI NIH HHS/ -- R01 GM083098/GM/NIGMS NIH HHS/ -- R01 HD021244/HD/NICHD NIH HHS/ -- R01 HL085197/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):836-40. doi: 10.1126/science.1183439. Epub 2009 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique Humaine, UPR1142, CNRS, Montpellier, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044539" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; DNA/chemistry/metabolism ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Genome ; Genome, Human ; Genotype ; Histone-Lysine N-Methyltransferase/chemistry/*genetics/*metabolism ; Humans ; Meiosis/*genetics ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Phenotype ; *Recombination, Genetic ; Zinc Fingers/genetics
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  • 5
    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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  • 6
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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〉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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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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〉Leslie, Mitch -- New York, N.Y. -- Science. 2010 Sep 24;329(5999):1595. doi: 10.1126/science.329.5999.1595.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929824" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/immunology ; Animals ; Antibodies/immunology ; *Antigen Presentation ; Antigen-Presenting Cells/immunology ; Basophils/*immunology ; Dendritic Cells/immunology ; Helminths/immunology ; Lymph Nodes/immunology ; Mice ; Th2 Cells/*immunology
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  • 8
    Publication Date: 2010-09-18
    Description: The mammalian cytoskeletal proteins beta- and gamma-actin are highly homologous, but only beta-actin is amino-terminally arginylated in vivo, which regulates its function. We examined the metabolic fate of exogenously expressed arginylated and nonarginylated actin isoforms. Arginylated gamma-actin, unlike beta-, was highly unstable and was selectively ubiquitinated and degraded in vivo. This instability was regulated by the differences in the nucleotide coding sequence between the two actin isoforms, which conferred different translation rates. gamma-actin was translated more slowly than beta-actin, and this slower processing resulted in the exposure of a normally hidden lysine residue for ubiquitination, leading to the preferential degradation of gamma-actin upon arginylation. This degradation mechanism, coupled to nucleotide coding sequence, may regulate protein arginylation in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941909/" 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/PMC2941909/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Fangliang -- Saha, Sougata -- Shabalina, Svetlana A -- Kashina, Anna -- 5R01HL084419/HL/NHLBI NIH HHS/ -- R01 HL084419/HL/NHLBI NIH HHS/ -- R01 HL084419-03/HL/NHLBI NIH HHS/ -- R01 HL084419-03S1/HL/NHLBI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Sep 17;329(5998):1534-7. doi: 10.1126/science.1191701.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20847274" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Animals ; Arginine/*metabolism ; Cell Line ; Cell Line, Tumor ; *Codon ; Humans ; Lysine/metabolism ; Mice ; Nucleic Acid Conformation ; Proteasome Endopeptidase Complex/metabolism ; Protein Biosynthesis ; Protein Folding ; Protein Isoforms/chemistry/genetics/metabolism ; *Protein Modification, Translational ; Protein Stability ; RNA, Messenger/chemistry/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Ubiquitination
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    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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  • 10
    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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  • 11
    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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  • 12
    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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  • 13
    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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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-04-17
    Description: When the food intake of organisms such as yeast and rodents is reduced (dietary restriction), they live longer than organisms fed a normal diet. A similar effect is seen when the activity of nutrient-sensing pathways is reduced by mutations or chemical inhibitors. In rodents, both dietary restriction and decreased nutrient-sensing pathway activity can lower the incidence of age-related loss of function and disease, including tumors and neurodegeneration. Dietary restriction also increases life span and protects against diabetes, cancer, and cardiovascular disease in rhesus monkeys, and in humans it causes changes that protect against these age-related pathologies. Tumors and diabetes are also uncommon in humans with mutations in the growth hormone receptor, and natural genetic variants in nutrient-sensing pathways are associated with increased human life span. Dietary restriction and reduced activity of nutrient-sensing pathways may thus slow aging by similar mechanisms, which have been conserved during evolution. We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607354/" 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/PMC3607354/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fontana, Luigi -- Partridge, Linda -- Longo, Valter D -- AG025135/AG/NIA NIH HHS/ -- AG20642/AG/NIA NIH HHS/ -- GM075308/GM/NIGMS NIH HHS/ -- P30 DK056341/DK/NIDDK NIH HHS/ -- P30DK056341/DK/NIDDK NIH HHS/ -- R01 AG020642/AG/NIA NIH HHS/ -- UL1 RR024992/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Apr 16;328(5976):321-6. doi: 10.1126/science.1172539.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO 63110, USA. lfontana@dom.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20395504" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Caenorhabditis elegans/genetics/physiology ; *Caloric Restriction ; Drosophila/genetics/physiology ; Eating ; Haplorhini ; Humans ; *Longevity ; Mice ; Saccharomyces cerevisiae/genetics/physiology ; *Signal Transduction
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  • 15
    Publication Date: 2010-05-15
    Description: Mycobacterium tuberculosis has a penetrance of its host population that would be the envy of most human pathogens. About one-third of the human population would have a positive skin test for the infection and is thus thought to harbor the bacterium. Globally, 22 "high-burden" countries account for more than 80% of the active tuberculosis cases in the world, which shows the inequitable distribution of the disease. There is no effective vaccine against infection, and current drug therapies are fraught with problems, predominantly because of the protracted nature of the treatment and the increasing occurrence of drug resistance. Here we focus on the biology of the host-pathogen interaction and discuss new and evolving strategies for intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872107/" 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/PMC2872107/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, David G -- Barry, Clifton E 3rd -- Flynn, JoAnne L -- AI057086/AI/NIAID NIH HHS/ -- AI067027/AI/NIAID NIH HHS/ -- AI080651/AI/NIAID NIH HHS/ -- AI50732/AI/NIAID NIH HHS/ -- HL055936/HL/NHLBI NIH HHS/ -- HL075845/HL/NHLBI NIH HHS/ -- HL092883/HL/NHLBI NIH HHS/ -- HL100928/HL/NHLBI NIH HHS/ -- HL71241/HL/NHLBI NIH HHS/ -- R01 AI037859/AI/NIAID NIH HHS/ -- R01 AI050732/AI/NIAID NIH HHS/ -- R01 AI050732-07/AI/NIAID NIH HHS/ -- R01 AI057086/AI/NIAID NIH HHS/ -- R01 AI057086-06A2/AI/NIAID NIH HHS/ -- R01 AI067027/AI/NIAID NIH HHS/ -- R01 AI067027-05/AI/NIAID NIH HHS/ -- R01 AI080651/AI/NIAID NIH HHS/ -- R01 AI080651-02/AI/NIAID NIH HHS/ -- R01 HL055936/HL/NHLBI NIH HHS/ -- R01 HL055936-14/HL/NHLBI NIH HHS/ -- R01 HL075845/HL/NHLBI NIH HHS/ -- R01 HL075845-05/HL/NHLBI NIH HHS/ -- R01 HL100928/HL/NHLBI NIH HHS/ -- R01 HL100928-01/HL/NHLBI NIH HHS/ -- R33 HL092883/HL/NHLBI NIH HHS/ -- R33 HL092883-02/HL/NHLBI NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 May 14;328(5980):852-6. doi: 10.1126/science.1184784.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. dgr8@cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466922" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antitubercular Agents/pharmacology/therapeutic use ; *BCG Vaccine/administration & dosage/immunology ; Biomarkers ; Disease Models, Animal ; Drug Discovery ; Drug Therapy, Combination ; Host-Pathogen Interactions ; Humans ; Mice ; *Mycobacterium tuberculosis/growth & development/immunology/metabolism ; Public Health Practice ; *Tuberculosis/drug therapy/immunology/microbiology/prevention & control ; Vaccination
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  • 16
    Publication Date: 2010-05-22
    Description: Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and experimental validation that rapid ligand depletion and replenishment of the cell surface receptor are characteristic features of the erythropoietin (Epo) receptor (EpoR). The amount of Epo-EpoR complexes and EpoR activation integrated over time corresponds linearly to ligand input; this process is carried out over a broad range of ligand concentrations. This relation depends solely on EpoR turnover independent of ligand binding, which suggests an essential role of large intracellular receptor pools. These receptor properties enable the system to cope with basal and acute demand in the hematopoietic system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Becker, Verena -- Schilling, Marcel -- Bachmann, Julie -- Baumann, Ute -- Raue, Andreas -- Maiwald, Thomas -- Timmer, Jens -- Klingmuller, Ursula -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1404-8. doi: 10.1126/science.1184913. Epub 2010 May 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20488988" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Membrane/*metabolism ; Computer Simulation ; Endocytosis ; Epoetin Alfa ; Erythropoietin/metabolism/pharmacology ; Kinetics ; Ligands ; Mice ; Models, Biological ; Protein Binding ; Receptors, Erythropoietin/*metabolism ; Recombinant Proteins ; Signal Transduction
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  • 17
    Publication Date: 2010-01-23
    Description: At the core of the mammalian circadian clock is a negative feedback loop in which the dimeric transcription factor CLOCK-BMAL1 drives processes that in turn suppress its transcriptional activity. To gain insight into the mechanisms of circadian feedback, we analyzed mouse protein complexes containing BMAL1. Receptor for activated C kinase-1 (RACK1) and protein kinase C-alpha (PKCalpha) were recruited in a circadian manner into a nuclear BMAL1 complex during the negative feedback phase of the cycle. Overexpression of RACK1 and PKCalpha suppressed CLOCK-BMAL1 transcriptional activity, and RACK1 stimulated phosphorylation of BMAL1 by PKCalpha in vitro. Depletion of endogenous RACK1 or PKCalpha from fibroblasts shortened the circadian period, demonstrating that both molecules function in the clock oscillatory mechanism. Thus, the classical PKC signaling pathway is not limited to relaying external stimuli but is rhythmically activated by internal processes, forming an integral part of the circadian feedback loop.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robles, Maria S -- Boyault, Cyril -- Knutti, Darko -- Padmanabhan, Kiran -- Weitz, Charles J -- New York, N.Y. -- Science. 2010 Jan 22;327(5964):463-6. doi: 10.1126/science.1180067.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20093473" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors/metabolism ; Animals ; CLOCK Proteins/metabolism ; Cell Nucleus/metabolism ; Circadian Rhythm/*physiology ; Feedback, Physiological ; Fibroblasts/metabolism/physiology ; Mice ; Mice, Inbred C57BL ; Neuropeptides/genetics/*metabolism ; Phosphorylation ; Protein Binding ; Protein Kinase C-alpha/*metabolism ; RNA Interference ; Signal Transduction ; Transcription, Genetic
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  • 18
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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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  • 19
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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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  • 20
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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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  • 21
    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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  • 22
    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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  • 23
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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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  • 24
    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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  • 25
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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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  • 27
    Publication Date: 2010-10-16
    Description: The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011229/" 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/PMC3011229/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lobo, Mary Kay -- Covington, Herbert E 3rd -- Chaudhury, Dipesh -- Friedman, Allyson K -- Sun, HaoSheng -- Damez-Werno, Diane -- Dietz, David M -- Zaman, Samir -- Koo, Ja Wook -- Kennedy, Pamela J -- Mouzon, Ezekiell -- Mogri, Murtaza -- Neve, Rachael L -- Deisseroth, Karl -- Han, Ming-Hu -- Nestler, Eric J -- P01 DA008227/DA/NIDA NIH HHS/ -- P01 DA008227-20/DA/NIDA NIH HHS/ -- R01 DA007359/DA/NIDA NIH HHS/ -- R01 DA007359-22/DA/NIDA NIH HHS/ -- R01 DA014133/DA/NIDA NIH HHS/ -- R01 DA014133-10/DA/NIDA NIH HHS/ -- R01 DA014133-11/DA/NIDA NIH HHS/ -- R01 DA014133-12/DA/NIDA NIH HHS/ -- R01 MH051399/MH/NIMH NIH HHS/ -- R01 MH051399-19/MH/NIMH NIH HHS/ -- R01 MH051399-20/MH/NIMH NIH HHS/ -- T32 DA007135-26A2/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):385-90. doi: 10.1126/science.1188472.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20947769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/drug effects ; Brain-Derived Neurotrophic Factor/*metabolism ; Cocaine/*pharmacology ; Cocaine-Related Disorders/*metabolism ; Conditioning (Psychology) ; Light ; Mice ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Models, Biological ; Motor Activity/drug effects ; Neurons/*metabolism ; Nucleus Accumbens/cytology/*metabolism ; RNA, Messenger/genetics/metabolism ; Receptor, trkB/genetics/*metabolism ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/metabolism ; *Reward ; Rhodopsin/genetics/metabolism ; *Signal Transduction
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-12-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gautel, Mathias -- Ehler, Elisabeth -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1491-2. doi: 10.1126/science.1199920.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉King's College London British Heart Foundation Centre of Research Excellence, Cardiovascular Division, London, SE1 1UL, UK. mathias.gautel@kcl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21148382" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Animals ; Connectin ; Insulin-Like Growth Factor I/*metabolism ; Mice ; Muscle Development ; Muscle Proteins/chemistry/*metabolism ; Protein Kinases/metabolism ; Sarcomeres/*metabolism/ultrastructure ; Wiskott-Aldrich Syndrome Protein, Neuronal/chemistry/*metabolism ; src Homology Domains
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  • 29
    Publication Date: 2010-01-02
    Description: Prions are infectious proteins consisting mainly of PrP(Sc), a beta sheet-rich conformer of the normal host protein PrP(C), and occur in different strains. Strain identity is thought to be encoded by PrP(Sc) conformation. We found that biologically cloned prion populations gradually became heterogeneous by accumulating "mutants," and selective pressures resulted in the emergence of different mutants as major constituents of the evolving population. Thus, when transferred from brain to cultured cells, "cell-adapted" prions outcompeted their "brain-adapted" counterparts, and the opposite occurred when prions were returned from cells to brain. Similarly, the inhibitor swainsonine selected for a resistant substrain, whereas, in its absence, the susceptible substrain outgrew its resistant counterpart. Prions, albeit devoid of a nucleic acid genome, are thus subject to mutation and selective amplification.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848070/" 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/PMC2848070/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Jiali -- Browning, Shawn -- Mahal, Sukhvir P -- Oelschlegel, Anja M -- Weissmann, Charles -- NS059543/NS/NINDS NIH HHS/ -- R01 NS059543/NS/NINDS NIH HHS/ -- R01 NS059543-01/NS/NINDS NIH HHS/ -- R01 NS059543-02/NS/NINDS NIH HHS/ -- R01 NS067214/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):869-72. doi: 10.1126/science.1183218. Epub 2009 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044542" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Brain Chemistry ; Cell Line ; Cell Line, Tumor ; Culture Media ; Culture Media, Conditioned ; *Evolution, Molecular ; Mice ; Mice, Inbred C57BL ; Mutation ; *PrPSc Proteins/chemistry/classification/pathogenicity ; Prion Diseases ; Prions/chemistry/classification/*pathogenicity/*physiology ; Protein Conformation ; Swainsonine/pharmacology
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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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  • 31
    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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    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Betz, Alexander G -- MC_U105184296/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1635-6. doi: 10.1126/science.1200406.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Protein & Nucleic Acid Chemistry Facility, University of Cambridge, Cambridge CB2 0QH, UK. betz@mrc-lmb.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21164004" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow/embryology/immunology/physiology ; Cell Lineage ; Fetal Development ; Fetus/*immunology ; Forkhead Transcription Factors/analysis/genetics ; Hematopoietic Stem Cells/*physiology ; Humans ; *Immune Tolerance ; Liver/embryology/immunology/physiology ; Lymphopoiesis ; Mice ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/*immunology ; T-Lymphocytes, Regulatory/*immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-04-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandoval, Darleen A -- Seeley, Randy J -- New York, N.Y. -- Science. 2010 Apr 9;328(5975):179-80. doi: 10.1126/science.1188876.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Metabolic Diseases Institute and Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45237, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20378804" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bacterial Physiological Phenomena ; Body Weight ; Disease Susceptibility ; Humans ; Immune System/*physiology ; Intestines/*microbiology ; Metabolic Syndrome X/*etiology/immunology/microbiology ; Mice ; Obesity/*etiology/immunology/microbiology ; Toll-Like Receptor 5/deficiency/genetics/*metabolism
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  • 35
    Publication Date: 2010-10-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tingen, C -- Rodriguez, S -- Campo-Engelstein, L -- Woodruff, T K -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):453. doi: 10.1126/science.1196881.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966235" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryo Research/*legislation & jurisprudence ; *Embryonic Stem Cells ; Female ; Financing, Government/legislation & jurisprudence ; Humans ; Mice ; Ovum/physiology ; *Parthenogenesis ; Research Support as Topic/*legislation & jurisprudence ; United States
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  • 36
    Publication Date: 2010-10-12
    Description: With the capacity for rapid self-renewal and regeneration, the intestinal epithelium is stereotypical of stem cell-supported tissues. Yet the pattern of stem cell turnover remains in question. Applying analytical methods from population dynamics and statistical physics to an inducible genetic labeling system, we showed that clone size distributions conform to a distinctive scaling behavior at short times. This result demonstrates that intestinal stem cells form an equipotent population in which the loss of a stem cell is compensated by the multiplication of a neighbor, leading to neutral drift dynamics in which clones expand and contract at random until they either take over the crypt or they are lost. Combined with long-term clonal fate data, we show that the rate of stem cell replacement is comparable to the cell division rate, implying that neutral drift and symmetrical cell divisions are central to stem cell homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Garcia, Carlos -- Klein, Allon M -- Simons, Benjamin D -- Winton, Douglas J -- G0800784/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):822-5. doi: 10.1126/science.1196236. Epub 2010 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929733" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; *Cell Division ; Cell Lineage ; Clone Cells/cytology ; Colon/cytology ; Homeostasis ; Intestinal Mucosa/*cytology ; Intestine, Small/cytology ; Mice ; Stem Cells/*cytology/physiology
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    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sauvageau, Guy -- Humphries, R Keith -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1291-2. doi: 10.1126/science.1195173.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Stem Cells Laboratory, Institute of Research in Immunology and Cancer, University of Montreal, Montreal, QC H3C 3J7, Canada. guy.sauvageau@umontreal.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829472" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD34/analysis ; Cell Lineage ; Cell Proliferation ; Cells, Cultured ; Fetal Blood/cytology ; *Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology/*drug effects/physiology ; Humans ; Mice ; Purines/chemistry/metabolism/*pharmacology ; Receptors, Aryl Hydrocarbon/*antagonists & inhibitors/metabolism ; Small Molecule Libraries ; Species Specificity
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  • 39
    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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  • 40
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-08-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhatia, Mickie -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1024-5. doi: 10.1126/science.1194919.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. mbhatia@mcmaster.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798306" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques/*methods ; Cell Differentiation ; Cell Division ; Cells, Cultured ; Elasticity ; Humans ; Hydrogels ; Mice ; Muscle Fibers, Skeletal/*cytology/physiology ; Myoblasts, Skeletal/cytology/physiology ; Regeneration ; Stem Cell Niche/*physiology ; Stem Cell Transplantation ; Stem Cells/*physiology
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  • 41
    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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  • 42
    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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  • 43
    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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  • 44
    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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  • 45
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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〉Veldhoen, Marc -- Withers, David R -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):594-5. doi: 10.1126/science.1198298.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, UK. marc.veldhoen@bbsrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21030634" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity ; Animals ; Cell Differentiation ; *Cell Lineage ; Fetus/cytology/immunology/metabolism ; Intestines/embryology/*immunology/microbiology ; Liver/cytology/immunology ; Lymphocyte Subsets/cytology/*immunology/metabolism ; Lymphocytes/cytology/*immunology/metabolism ; Lymphoid Progenitor Cells/*cytology ; Lymphoid Tissue/cytology/immunology ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
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  • 46
    Publication Date: 2010-01-16
    Description: Integrins mediate cell adhesion to the extracellular matrix and transmit signals within the cell that stimulate cell spreading, retraction, migration, and proliferation. The mechanism of integrin outside-in signaling has been unclear. We found that the heterotrimeric guanine nucleotide-binding protein (G protein) Galpha13 directly bound to the integrin beta3 cytoplasmic domain and that Galpha13-integrin interaction was promoted by ligand binding to the integrin alphaIIbbeta3 and by guanosine triphosphate (GTP) loading of Galpha13. Interference of Galpha13 expression or a myristoylated fragment of Galpha13 that inhibited interaction of alphaIIbbeta3 with Galpha13 diminished activation of protein kinase c-Src and stimulated the small guanosine triphosphatase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are noncanonical Galpha13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842917/" 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/PMC2842917/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Haixia -- Shen, Bo -- Flevaris, Panagiotis -- Chow, Christina -- Lam, Stephen C-T -- Voyno-Yasenetskaya, Tatyana A -- Kozasa, Tohru -- Du, Xiaoping -- GM061454/GM/NIGMS NIH HHS/ -- GM074001/GM/NIGMS NIH HHS/ -- HL062350/HL/NHLBI NIH HHS/ -- HL068819/HL/NHLBI NIH HHS/ -- HL080264/HL/NHLBI NIH HHS/ -- R01 GM061454/GM/NIGMS NIH HHS/ -- R01 GM061454-09/GM/NIGMS NIH HHS/ -- R01 GM074001/GM/NIGMS NIH HHS/ -- R01 GM074001-02/GM/NIGMS NIH HHS/ -- R01 HL062350/HL/NHLBI NIH HHS/ -- R01 HL062350-09/HL/NHLBI NIH HHS/ -- R01 HL068819/HL/NHLBI NIH HHS/ -- R01 HL068819-08/HL/NHLBI NIH HHS/ -- R01 HL080264/HL/NHLBI NIH HHS/ -- R01 HL080264-04/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jan 15;327(5963):340-3. doi: 10.1126/science.1174779.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Illinois at Chicago, 835 South Wolcott Avenue, Room E403, Chicago, IL 60612, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20075254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Blood Platelets/*physiology ; Clot Retraction ; Fibrinogen/metabolism ; GTP-Binding Protein alpha Subunits, G12-G13/genetics/*metabolism ; Humans ; Integrin beta3/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Platelet Adhesiveness ; Platelet Glycoprotein GPIIb-IIIa Complex/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Proto-Oncogene Proteins pp60(c-src)/metabolism ; RNA, Small Interfering ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction ; rhoA GTP-Binding Protein/antagonists & inhibitors/metabolism
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  • 47
    Publication Date: 2010-10-12
    Description: Lymphoid tissue-inducer (LTi) cells initiate the development of lymphoid tissues through the activation of local stromal cells in a process similar to inflammation. LTi cells express the nuclear hormone receptor RORgammat, which also directs the expression of the proinflammatory cytokine interleukin-17 in T cells. We show here that LTi cells are part of a larger family of proinflammatory RORgammat(+) innate lymphoid cells (ILCs) that differentiate from distinct fetal liver RORgammat(+) precursors. The fate of RORgammat(+) ILCs is determined by mouse age, and after birth, favors the generation of cells involved in intestinal homeostasis and defense. Contrary to RORgammat(+) T cells, however, RORgammat(+) ILCs develop in the absence of microbiota. Our study indicates that RORgammat(+) ILCs evolve to preempt intestinal colonization by microbial symbionts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sawa, Shinichiro -- Cherrier, Marie -- Lochner, Matthias -- Satoh-Takayama, Naoko -- Fehling, Hans Jorg -- Langa, Francina -- Di Santo, James P -- Eberl, Gerard -- New York, N.Y. -- Science. 2010 Oct 29;330(6004):665-9. doi: 10.1126/science.1194597. Epub 2010 Sep 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphoid Tissue Development Unit, Institut Pasteur, 75724 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929731" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptive Immunity ; Adoptive Transfer ; Animals ; Bacterial Physiological Phenomena ; Cell Differentiation ; Cell Lineage ; Fetus/cytology/immunology/metabolism ; Homeostasis ; Immunity, Mucosal ; Intestinal Mucosa/*immunology ; Intestine, Small/embryology/*immunology/microbiology ; Liver/cytology/embryology/immunology ; Lymphocyte Subsets/cytology/*immunology/metabolism ; Lymphocytes/cytology/*immunology/metabolism ; Lymphoid Progenitor Cells/*cytology ; Lymphoid Tissue/cytology/immunology ; Lymphopoiesis ; Mice ; Mice, Transgenic ; Nuclear Receptor Subfamily 1, Group F, Member 3/*metabolism ; Receptors, CCR6/metabolism ; Symbiosis ; T-Lymphocyte Subsets/cytology/immunology/metabolism
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  • 48
    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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  • 49
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    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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  • 50
    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
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 51
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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〉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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  • 52
    Publication Date: 2010-08-21
    Description: Nuclei move to specific locations to polarize migrating and differentiating cells. Many nuclear movements are microtubule-dependent. However, nuclear movement to reorient the centrosome in migrating fibroblasts occurs through an unknown actin-dependent mechanism. We found that linear arrays of outer (nesprin2G) and inner (SUN2) nuclear membrane proteins assembled on and moved with retrogradely moving dorsal actin cables during nuclear movement in polarizing fibroblasts. Inhibition of nesprin2G, SUN2, or actin prevented nuclear movement and centrosome reorientation. The coupling of actin cables to the nuclear membrane for nuclear movement via specific membrane proteins indicates that, like plasma membrane integrins, nuclear membrane proteins assemble into actin-dependent arrays for force transduction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938394/" 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/PMC3938394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luxton, G W Gant -- Gomes, Edgar R -- Folker, Eric S -- Vintinner, Erin -- Gundersen, Gregg G -- GM06929/GM/NIGMS NIH HHS/ -- NS059352/NS/NINDS NIH HHS/ -- R01 GM062939/GM/NIGMS NIH HHS/ -- R01 GM099481/GM/NIGMS NIH HHS/ -- R01 NS059352/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 20;329(5994):956-9. doi: 10.1126/science.1189072.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20724637" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*metabolism ; Animals ; Cell Movement/physiology ; Cell Nucleus/*metabolism ; Centrosome/physiology ; Fibroblasts ; Lysophospholipids/metabolism ; Membrane Proteins/metabolism ; Mice ; Movement ; NIH 3T3 Cells ; Nerve Tissue Proteins/metabolism ; Nuclear Envelope/*metabolism ; Nuclear Proteins/*metabolism ; Telomere-Binding Proteins/metabolism
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  • 53
    Publication Date: 2010-10-12
    Description: Lymphocyte survival during immune responses is controlled by the relative expression of pro- and anti-apoptotic molecules, regulating the magnitude, quality, and duration of the response. We investigated the consequences of deleting genes encoding the anti-apoptotic molecules Mcl1 and Bcl2l1 (Bcl-x(L)) from B cells using an inducible system synchronized with expression of activation-induced cytidine deaminase (Aicda) after immunization. This revealed Mcl1 and not Bcl2l1 to be indispensable for the formation and persistence of germinal centers (GCs). Limiting Mcl1 expression reduced the magnitude of the GC response with an equivalent, but not greater, effect on memory B cell formation and no effect on persistence. Our results identify Mcl1 as the main anti-apoptotic regulator of activated B cell survival and suggest distinct mechanisms controlling survival of GC and memory B cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991396/" 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/PMC2991396/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vikstrom, Ingela -- Carotta, Sebastian -- Luthje, Katja -- Peperzak, Victor -- Jost, Philipp J -- Glaser, Stefan -- Busslinger, Meinrad -- Bouillet, Philippe -- Strasser, Andreas -- Nutt, Stephen L -- Tarlinton, David M -- CA43540/CA/NCI NIH HHS/ -- CA80188/CA/NCI NIH HHS/ -- R01 CA043540/CA/NCI NIH HHS/ -- R01 CA043540-22/CA/NCI NIH HHS/ -- R01 CA080188-08/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Nov 19;330(6007):1095-9. doi: 10.1126/science.1191793. Epub 2010 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929728" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Affinity ; B-Lymphocytes/*immunology ; Cell Survival ; Gene Deletion ; Germinal Center/cytology/*immunology ; *Immunologic Memory ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2/genetics/*immunology ; bcl-X Protein/genetics/immunology
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  • 54
    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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  • 55
    Publication Date: 2010-07-31
    Description: During embryonic development, many organs form by extensive branching of epithelia through the formation of clefts and buds. In cleft formation, buds are delineated by the conversion of epithelial cell-cell adhesions to cell-matrix adhesions, but the mechanisms of cleft formation are not clear. We have identified Btbd7 as a dynamic regulator of branching morphogenesis. Btbd7 provides a mechanistic link between the extracellular matrix and cleft propagation through its highly focal expression leading to local regulation of Snail2 (Slug), E-cadherin, and epithelial cell motility. Inhibition experiments show that Btbd7 is required for branching of embryonic mammalian salivary glands and lungs. Hence, Btbd7 is a regulatory gene that promotes epithelial tissue remodeling and formation of branched organs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412157/" 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/PMC3412157/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onodera, Tomohiro -- Sakai, Takayoshi -- Hsu, Jeff Chi-feng -- Matsumoto, Kazue -- Chiorini, John A -- Yamada, Kenneth M -- ZIA DE000525-20/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 30;329(5991):562-5. doi: 10.1126/science.1191880.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671187" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cadherins/metabolism ; Cell Adhesion ; Cell Line ; Cell Movement ; Dogs ; Epithelial Cells/*physiology ; Fibronectins/genetics/metabolism ; Genes, Regulator ; Lung/*embryology/metabolism ; Mice ; Mice, Inbred ICR ; Models, Biological ; Molecular Sequence Data ; *Morphogenesis ; Nuclear Proteins ; Organ Culture Techniques ; Proteins/chemistry/*genetics/*physiology ; RNA, Small Interfering ; Salivary Glands/*embryology/metabolism ; Submandibular Gland/embryology ; Transcription Factors/genetics/metabolism ; Transfection
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  • 56
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    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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  • 57
    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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  • 58
    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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  • 59
    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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  • 60
    Publication Date: 2010-01-30
    Description: In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles--submicrometer vesicles elaborated by activated platelets--in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927861/" 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/PMC2927861/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boilard, Eric -- Nigrovic, Peter A -- Larabee, Katherine -- Watts, Gerald F M -- Coblyn, Jonathan S -- Weinblatt, Michael E -- Massarotti, Elena M -- Remold-O'Donnell, Eileen -- Farndale, Richard W -- Ware, Jerry -- Lee, David M -- G0500707/Medical Research Council/United Kingdom -- HL091269/HL/NHLBI NIH HHS/ -- HL50545/HL/NHLBI NIH HHS/ -- K08AR051321/AR/NIAMS NIH HHS/ -- P01 AI065858/AI/NIAID NIH HHS/ -- R01 HL050545/HL/NHLBI NIH HHS/ -- R01 HL050545-16/HL/NHLBI NIH HHS/ -- R01 HL050545-18/HL/NHLBI NIH HHS/ -- R21 HL091269/HL/NHLBI NIH HHS/ -- R21 HL091269-01A2/HL/NHLBI NIH HHS/ -- RG/09/003/27122/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Jan 29;327(5965):580-3. doi: 10.1126/science.1181928.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20110505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/blood/immunology ; Arthritis, Rheumatoid/*blood/*immunology/physiopathology ; Blood Platelets/cytology/*physiology/ultrastructure ; Cell-Derived Microparticles/metabolism/*physiology ; Cells, Cultured ; Collagen/*metabolism ; Cytokines/*metabolism ; Extracellular Matrix/metabolism ; Fibroblasts/immunology/metabolism ; Humans ; Interleukin-1/metabolism ; Mice ; Mice, Transgenic ; Platelet Activation ; Platelet Membrane Glycoproteins/metabolism ; Receptors, Collagen/metabolism ; Synovial Fluid/cytology/*immunology ; Synovial Membrane/cytology/immunology
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  • 61
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patel, Anand G -- Kaufmann, Scott H -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):766-7. doi: 10.1126/science.1198310.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051622" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents, Phytogenic/administration & dosage/*metabolism/toxicity ; Bacteria/drug effects/enzymology ; Camptothecin/administration & dosage/*analogs & derivatives/metabolism/toxicity ; Drug Evaluation, Preclinical ; Enzyme Inhibitors/*pharmacology ; Escherichia coli/drug effects/enzymology ; Glucuronidase/*antagonists & inhibitors ; Intestinal Mucosa/drug effects/metabolism/*microbiology ; Mice
    Print ISSN: 0036-8075
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  • 62
    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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  • 63
    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
    Print ISSN: 0036-8075
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  • 64
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregg, Christopher -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):770-1. doi: 10.1126/science.1199054.〈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/21051625" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Awards and Prizes ; *Fathers ; *Gene Expression ; Gene Expression Profiling ; *Genomic Imprinting ; Humans ; Interleukin-18 ; Mice ; Mice, Inbred C57BL ; *Mothers ; Polymorphism, Single Nucleotide ; Prefrontal Cortex/embryology/growth & development/*metabolism ; Preoptic Area/embryology/growth & development/*metabolism ; Sex Characteristics
    Print ISSN: 0036-8075
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  • 65
    Publication Date: 2010-01-23
    Description: Wnt/beta-catenin signaling is important in stem cell biology, embryonic development, and disease, including cancer. However, the mechanism of Wnt signal transmission, notably how the receptors are activated, remains incompletely understood. We found that the prorenin receptor (PRR) is a component of the Wnt receptor complex. PRR functions in a renin-independent manner as an adaptor between Wnt receptors and the vacuolar H+-adenosine triphosphatase (V-ATPase) complex. Moreover, PRR and V-ATPase were required to mediate Wnt signaling during antero-posterior patterning of Xenopus early central nervous system development. The results reveal an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/beta-catenin signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cruciat, Cristina-Maria -- Ohkawara, Bisei -- Acebron, Sergio P -- Karaulanov, Emil -- Reinhard, Carmen -- Ingelfinger, Dierk -- Boutros, Michael -- Niehrs, Christof -- New York, N.Y. -- Science. 2010 Jan 22;327(5964):459-63. doi: 10.1126/science.1179802.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20093472" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Patterning ; Cell Line ; Cell Line, Tumor ; Central Nervous System/cytology/embryology ; Embryo, Nonmammalian/metabolism ; Frizzled Receptors/metabolism ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/genetics/metabolism ; Humans ; Hydrogen-Ion Concentration ; LDL-Receptor Related Proteins/metabolism ; Low Density Lipoprotein Receptor-Related Protein-6 ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Phosphorylation ; RNA, Small Interfering ; Receptors, Cell Surface/genetics/*metabolism ; *Signal Transduction ; Vacuolar Proton-Translocating ATPases/antagonists & inhibitors/*metabolism ; Wnt Proteins/*metabolism ; Wnt3 Protein ; Xenopus/embryology/metabolism ; Xenopus Proteins/genetics/*metabolism ; beta Catenin/metabolism
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  • 66
    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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  • 67
    Publication Date: 2010-07-22
    Description: Stem cells that naturally reside in adult tissues, such as muscle stem cells (MuSCs), exhibit robust regenerative capacity in vivo that is rapidly lost in culture. Using a bioengineered substrate to recapitulate key biophysical and biochemical niche features in conjunction with a highly automated single-cell tracking algorithm, we show that substrate elasticity is a potent regulator of MuSC fate in culture. Unlike MuSCs on rigid plastic dishes (approximately 10(6) kilopascals), MuSCs cultured on soft hydrogel substrates that mimic the elasticity of muscle (12 kilopascals) self-renew in vitro and contribute extensively to muscle regeneration when subsequently transplanted into mice and assayed histologically and quantitatively by noninvasive bioluminescence imaging. Our studies provide novel evidence that by recapitulating physiological tissue rigidity, propagation of adult muscle stem cells is possible, enabling future cell-based therapies for muscle-wasting diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929271/" 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/PMC2929271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilbert, P M -- Havenstrite, K L -- Magnusson, K E G -- Sacco, A -- Leonardi, N A -- Kraft, P -- Nguyen, N K -- Thrun, S -- Lutolf, M P -- Blau, H M -- 2 T32 HD007249/HD/NICHD NIH HHS/ -- 52005886/Howard Hughes Medical Institute/ -- AG009521/AG/NIA NIH HHS/ -- AG020961/AG/NIA NIH HHS/ -- CA09151/CA/NCI NIH HHS/ -- HL096113/HL/NHLBI NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG020961/AG/NIA NIH HHS/ -- R01 AG020961-06A2/AG/NIA NIH HHS/ -- R01 AG020961-07/AG/NIA NIH HHS/ -- R01 HL096113/HL/NHLBI NIH HHS/ -- R01 HL096113-03/HL/NHLBI NIH HHS/ -- T32 CA009151/CA/NCI NIH HHS/ -- T32 CA009151-35/CA/NCI NIH HHS/ -- T32 HD007249/HD/NICHD NIH HHS/ -- T32 HD007249-25/HD/NICHD NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- U01 HL100397-01/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1078-81. doi: 10.1126/science.1191035. Epub 2010 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647425" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Cell Count ; Cell Culture Techniques/*methods ; Cell Death ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Separation ; Cell Survival ; Cells, Cultured ; Elastic Modulus ; Hydrogels ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; Muscle Fibers, Skeletal/*cytology/physiology ; Muscle, Skeletal/*cytology ; Polyethylene Glycols ; Regeneration ; Satellite Cells, Skeletal Muscle/cytology ; Stem Cell Niche/*physiology ; Stem Cell Transplantation ; Stem Cells/cytology/*physiology
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  • 68
    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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  • 69
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2010 Mar 5;327(5970):1191. doi: 10.1126/science.327.5970.1191.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20203025" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Line ; *Cellular Reprogramming ; Embryonic Stem Cells/cytology/*physiology ; Humans ; Induced Pluripotent Stem Cells/cytology/*physiology ; Mice ; Neurogenesis ; Neuroglia/cytology ; Neurons/cytology
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  • 70
    Publication Date: 2010-03-27
    Description: Shelterin is an essential telomeric protein complex that prevents DNA damage signaling and DNA repair at mammalian chromosome ends. Here we report on the role of the TRF2-interacting factor Rap1, a conserved shelterin subunit of unknown function. We removed Rap1 from mouse telomeres either through gene deletion or by replacing TRF2 with a mutant that does not bind Rap1. Rap1 was dispensable for the essential functions of TRF2--repression of ATM kinase signaling and nonhomologous end joining (NHEJ)--and mice lacking telomeric Rap1 were viable and fertile. However, Rap1 was critical for the repression of homology-directed repair (HDR), which can alter telomere length. The data reveal that HDR at telomeres can take place in the absence of DNA damage foci and underscore the functional compartmentalization within shelterin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864730/" 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/PMC2864730/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sfeir, Agnel -- Kabir, Shaheen -- van Overbeek, Megan -- Celli, Giulia B -- de Lange, Titia -- AG016642/AG/NIA NIH HHS/ -- GM049046/GM/NIGMS NIH HHS/ -- R01 AG016642/AG/NIA NIH HHS/ -- R01 AG016642-01/AG/NIA NIH HHS/ -- R01 AG016642-02/AG/NIA NIH HHS/ -- R01 AG016642-03/AG/NIA NIH HHS/ -- R01 AG016642-04/AG/NIA NIH HHS/ -- R01 AG016642-05/AG/NIA NIH HHS/ -- R01 AG016642-06/AG/NIA NIH HHS/ -- R01 AG016642-07/AG/NIA NIH HHS/ -- R01 AG016642-08/AG/NIA NIH HHS/ -- R01 AG016642-09/AG/NIA NIH HHS/ -- R01 AG016642-10/AG/NIA NIH HHS/ -- R01 AG016642-11/AG/NIA NIH HHS/ -- R01 GM049046/GM/NIGMS NIH HHS/ -- R01 GM049046-07/GM/NIGMS NIH HHS/ -- R01 GM049046-08/GM/NIGMS NIH HHS/ -- R01 GM049046-09/GM/NIGMS NIH HHS/ -- R01 GM049046-10/GM/NIGMS NIH HHS/ -- R01 GM049046-11/GM/NIGMS NIH HHS/ -- R01 GM049046-12/GM/NIGMS NIH HHS/ -- R37 GM049046/GM/NIGMS NIH HHS/ -- R37 GM049046-13/GM/NIGMS NIH HHS/ -- R37 GM049046-14/GM/NIGMS NIH HHS/ -- R37 GM049046-15/GM/NIGMS NIH HHS/ -- R37 GM049046-16/GM/NIGMS NIH HHS/ -- R37 GM049046-17/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1657-61. doi: 10.1126/science.1185100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339076" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/metabolism ; Cell Proliferation ; Cells, Cultured ; Checkpoint Kinase 2 ; *DNA Damage ; *DNA Repair ; DNA-Binding Proteins/metabolism ; Gene Deletion ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Protein-Serine-Threonine Kinases/metabolism ; Recombination, Genetic ; Signal Transduction ; Sister Chromatid Exchange ; Telomere/*genetics/metabolism ; Telomere-Binding Proteins/chemistry/*genetics/*metabolism ; Telomeric Repeat Binding Protein 2/genetics/metabolism ; Tumor Suppressor Proteins/metabolism
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  • 71
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Culjkovic-Kraljacic, Bijana -- Borden, Katherine L B -- R01 CA080728/CA/NCI NIH HHS/ -- R01 CA098571/CA/NCI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Nov 26;330(6008):1183-4. doi: 10.1126/science.1199405.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Research in Immunology and Cancer, Department of Pathology and Cell Biology, Universite de Montreal, Pavillion Marcelle-Coutu, Chemin Polytechnique, Montreal, QC, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21109655" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Calcium/*metabolism ; *Calcium Signaling ; Endoplasmic Reticulum/*metabolism ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Intranuclear Space/metabolism ; Mice ; Mitochondria/metabolism ; Nuclear Proteins/*metabolism ; Phosphorylation ; Protein Isoforms/metabolism ; Transcription Factors/*metabolism ; Tumor Suppressor Proteins/*metabolism
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  • 72
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-11-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schreiber, Hans -- Rowley, Donald A -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):761-2. doi: 10.1126/science.1198345.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, The University of Chicago, Chicago, IL 60637, USA. hszz@midway.uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051618" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/immunology ; Autoantigens/immunology ; Cytokines/metabolism ; Fibroblasts/immunology/metabolism/*physiology ; Gelatinases/*metabolism ; Immune Tolerance ; Lymphocytes, Tumor-Infiltrating/*immunology/metabolism ; Membrane Proteins/*metabolism ; Mice ; Neoplasm Transplantation ; Neoplasms, Experimental/*immunology/metabolism/pathology ; Serine Endopeptidases/*metabolism ; Stromal Cells/*immunology/metabolism ; T-Lymphocytes/*immunology/metabolism
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  • 73
    Publication Date: 2010-06-19
    Description: Adipose tissue secretes proteins referred to as adipokines, many of which promote inflammation and disrupt glucose homeostasis. Here we show that secreted frizzled-related protein 5 (Sfrp5), a protein previously linked to the Wnt signaling pathway, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes. Sfrp5-deficient mice fed a high-calorie diet developed severe glucose intolerance and hepatic steatosis, and their adipose tissue showed an accumulation of activated macrophages that was associated with activation of the c-Jun N-terminal kinase signaling pathway. Adenovirus-mediated delivery of Sfrp5 to mouse models of obesity ameliorated glucose intolerance and hepatic steatosis. Thus, in the setting of obesity, Sfrp5 secretion by adipocytes exerts salutary effects on metabolic dysfunction by controlling inflammatory cells within adipose tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132938/" 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/PMC3132938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ouchi, Noriyuki -- Higuchi, Akiko -- Ohashi, Koji -- Oshima, Yuichi -- Gokce, Noyan -- Shibata, Rei -- Akasaki, Yuichi -- Shimono, Akihiko -- Walsh, Kenneth -- AG15052/AG/NIA NIH HHS/ -- AG34972/AG/NIA NIH HHS/ -- HL81587/HL/NHLBI NIH HHS/ -- HL86785/HL/NHLBI NIH HHS/ -- P01 HL081587/HL/NHLBI NIH HHS/ -- P01 HL081587-05/HL/NHLBI NIH HHS/ -- R01 AG015052/AG/NIA NIH HHS/ -- R01 AG015052-06/AG/NIA NIH HHS/ -- R01 AG034972/AG/NIA NIH HHS/ -- R01 AG034972-03/AG/NIA NIH HHS/ -- R01 HL086785/HL/NHLBI NIH HHS/ -- R01 HL086785-19/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):454-7. doi: 10.1126/science.1188280. Epub 2010 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Cardiology and Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. nouchi@bu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20558665" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/*metabolism/pathology ; Adipokines/genetics/*metabolism ; Adipose Tissue/*metabolism/pathology ; Animals ; Dietary Fats/administration & dosage ; Dietary Sucrose/administration & dosage ; Fatty Liver/pathology/therapy ; Genetic Vectors ; Glucose/metabolism ; Humans ; Inflammation ; Insulin/metabolism ; Insulin Resistance ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Macrophages/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Mitogen-Activated Protein Kinase 8/genetics/metabolism ; Obesity/*metabolism/pathology ; Phosphorylation ; Rats ; Rats, Zucker ; Signal Transduction ; Wnt Proteins/metabolism
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  • 74
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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〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1619. doi: 10.1126/science.330.6011.1619.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21163991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Bacterial Physiological Phenomena ; Digestive System/microbiology ; Genes, Bacterial ; Genome, Bacterial ; Humans ; Immune System/physiology ; Metagenome/*physiology ; Metagenomics ; Mice ; Sequence Analysis, DNA ; *Virus Physiological Phenomena
    Print ISSN: 0036-8075
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  • 75
    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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  • 76
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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〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2010 Dec 17;330(6011):1614. doi: 10.1126/science.330.6011.1614.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21163986" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA, Intergenic/*genetics ; *Gene Expression Regulation ; *Genome ; *Genome, Human ; Humans ; Mice ; RNA Interference ; RNA, Untranslated/*genetics
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  • 77
    Publication Date: 2010-08-28
    Description: Presynaptic nerve terminals release neurotransmitters repeatedly, often at high frequency, and in relative isolation from neuronal cell bodies. Repeated release requires cycles of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-complex assembly and disassembly, with continuous generation of reactive SNARE-protein intermediates. Although many forms of neurodegeneration initiate presynaptically, only few pathogenic mechanisms are known, and the functions of presynaptic proteins linked to neurodegeneration, such as alpha-synuclein, remain unclear. Here, we show that maintenance of continuous presynaptic SNARE-complex assembly required a nonclassical chaperone activity mediated by synucleins. Specifically, alpha-synuclein directly bound to the SNARE-protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and promoted SNARE-complex assembly. Moreover, triple-knockout mice lacking synucleins developed age-dependent neurological impairments, exhibited decreased SNARE-complex assembly, and died prematurely. Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235365/" 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/PMC3235365/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burre, Jacqueline -- Sharma, Manu -- Tsetsenis, Theodoros -- Buchman, Vladimir -- Etherton, Mark R -- Sudhof, Thomas C -- 075615/Wellcome Trust/United Kingdom -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Sep 24;329(5999):1663-7. doi: 10.1126/science.1195227. Epub 2010 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798282" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Cell Line ; Cells, Cultured ; HSP40 Heat-Shock Proteins/metabolism ; Humans ; Membrane Fusion ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Nerve Degeneration/*metabolism ; Neurons/*metabolism ; Presynaptic Terminals/*metabolism ; Protein Binding ; Rats ; Recombinant Fusion Proteins/metabolism ; SNARE Proteins/*metabolism ; Vesicle-Associated Membrane Protein 2/metabolism ; alpha-Synuclein/chemistry/genetics/*metabolism
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  • 78
    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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  • 79
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    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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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-09-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, Andrey S -- Huang, Yina -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Sep 3;329(5996):1154-5. doi: 10.1126/science.1195337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology and Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA. shaw@pathology.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20813941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Adhesion Molecules/chemistry/*metabolism ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Crystallization ; Epidermis/*immunology/metabolism/ultrastructure ; Hydrogen Bonding ; Ligands ; Lymphocyte Activation ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Receptors, Antigen, T-Cell, gamma-delta/*immunology/metabolism ; Receptors, Virus/chemistry/*metabolism ; Signal Transduction ; T-Lymphocyte Subsets/*immunology/*metabolism ; Tight Junctions/metabolism
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  • 81
    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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  • 82
    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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  • 83
    Publication Date: 2010-07-31
    Description: Programmed genetic rearrangements in lymphocytes require transcription at antigen receptor genes to promote accessibility for initiating double-strand break (DSB) formation critical for DNA recombination and repair. Here, we showed that activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage leukemia 3)-MLL4 complex display impaired trimethylation of histone 3 at lysine 4 (H3K4me3) and transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus, leading to defective immunoglobulin class switching. We also showed that PTIP accumulation at DSBs contributes to class switch recombination (CSR) and genome stability independently of Igh switch transcription. These results demonstrate that PTIP promotes specific chromatin changes that control the accessibility of the Igh locus to CSR and suggest a nonredundant role for the MLL3-MLL4 complex in altering antibody effector function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008398/" 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/PMC3008398/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daniel, Jeremy A -- Santos, Margarida Almeida -- Wang, Zhibin -- Zang, Chongzhi -- Schwab, Kristopher R -- Jankovic, Mila -- Filsuf, Darius -- Chen, Hua-Tang -- Gazumyan, Anna -- Yamane, Arito -- Cho, Young-Wook -- Sun, Hong-Wei -- Ge, Kai -- Peng, Weiqun -- Nussenzweig, Michel C -- Casellas, Rafael -- Dressler, Gregory R -- Zhao, Keji -- Nussenzweig, Andre -- Z01 AR041149-03/Intramural NIH HHS/ -- Z01 AR041149-04/Intramural NIH HHS/ -- Z01 DK047055-01/Intramural NIH HHS/ -- Z01 DK047055-02/Intramural NIH HHS/ -- Z01 DK075003-04/Intramural NIH HHS/ -- Z01 DK075003-05/Intramural NIH HHS/ -- Z99 DK999999/Intramural NIH HHS/ -- ZIA AR041149-05/Intramural NIH HHS/ -- ZIA DK075017-03/Intramural NIH HHS/ -- ZIADK047055-03/DK/NIDDK NIH HHS/ -- ZIADK075003-06/DK/NIDDK NIH HHS/ -- ZIADK075017-01/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Aug 20;329(5994):917-23. doi: 10.1126/science.1187942. Epub 2010 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20671152" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody Specificity/genetics ; Carrier Proteins/genetics/*physiology ; Cytidine Deaminase/metabolism ; Dna ; Histones/metabolism ; Immunoglobulin Class Switching/genetics/*physiology ; Immunoglobulin Switch Region ; Methylation ; Mice ; Nuclear Proteins/genetics/*physiology ; Promoter Regions, Genetic ; Recombination, Genetic ; Transcriptional Activation
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  • 84
    Publication Date: 2010-01-23
    Description: The LMO2 oncogene causes a subset of human T cell acute lymphoblastic leukemias (T-ALL), including four cases that arose as adverse events in gene therapy trials. To investigate the cellular origin of LMO2-induced leukemia, we used cell fate mapping to study mice in which the Lmo2 gene was constitutively expressed in the thymus. Lmo2 induced self-renewal of committed T cells in the mice more than 8 months before the development of overt T-ALL. These self-renewing cells retained the capacity for T cell differentiation but expressed several genes typical of hematopoietic stem cells (HSCs), suggesting that Lmo2 might reactivate an HSC-specific transcriptional program. Forced expression of one such gene, Hhex, was sufficient to initiate self-renewal of thymocytes in vivo. Thus, Lmo2 promotes the self-renewal of preleukemic thymocytes, providing a mechanism by which committed T cells can then accumulate additional genetic mutations required for leukemic transformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCormack, Matthew P -- Young, Lauren F -- Vasudevan, Sumitha -- de Graaf, Carolyn A -- Codrington, Rosalind -- Rabbitts, Terence H -- Jane, Stephen M -- Curtis, David J -- G0600914/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Feb 12;327(5967):879-83. doi: 10.1126/science.1182378. Epub 2010 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rotary Bone Marrow Research Laboratories, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. mccormack@wehi.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20093438" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Cell Differentiation ; Cell Transformation, Neoplastic/*genetics ; DNA-Binding Proteins/*genetics/metabolism ; Down-Regulation ; Gene Expression Profiling ; Gene Expression Regulation, Leukemic ; Homeodomain Proteins/genetics ; Humans ; LIM Domain Proteins ; Metalloproteins/*genetics/metabolism ; Mice ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; *Oncogenes ; Precursor Cells, T-Lymphoid/*physiology/transplantation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/metabolism/pathology ; Preleukemia/genetics/metabolism/pathology ; Proto-Oncogene Proteins ; T-Lymphocyte Subsets ; T-Lymphocytes/*physiology/transplantation ; Thymus Gland/metabolism/pathology ; Transcription Factors/genetics ; Transcription, Genetic ; Up-Regulation
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  • 85
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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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  • 86
    Publication Date: 2010-06-26
    Description: Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Busskamp, Volker -- Duebel, Jens -- Balya, David -- Fradot, Mathias -- Viney, Tim James -- Siegert, Sandra -- Groner, Anna C -- Cabuy, Erik -- Forster, Valerie -- Seeliger, Mathias -- Biel, Martin -- Humphries, Peter -- Paques, Michel -- Mohand-Said, Saddek -- Trono, Didier -- Deisseroth, Karl -- Sahel, Jose A -- Picaud, Serge -- Roska, Botond -- New York, N.Y. -- Science. 2010 Jul 23;329(5990):413-7. doi: 10.1126/science.1190897. Epub 2010 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20576849" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dependovirus/genetics ; Disease Models, Animal ; Evoked Potentials, Visual ; *Genetic Therapy ; Genetic Vectors ; Halobacteriaceae/genetics ; Halorhodopsins/*genetics/*metabolism ; Humans ; Light ; Mice ; Mice, Knockout ; Promoter Regions, Genetic ; Retina/physiology ; Retinal Cone Photoreceptor Cells/*physiology ; Retinal Ganglion Cells/physiology ; Retinitis Pigmentosa/physiopathology/*therapy ; Tissue Culture Techniques ; Transfection ; Vision, Ocular ; Visual Pathways/physiology
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  • 87
    Publication Date: 2010-02-27
    Description: CKAMP44, identified here by a proteomic approach, is a brain-specific type I transmembrane protein that associates with AMPA receptors in synaptic spines. CKAMP44 expressed in Xenopus oocytes reduced GluA1- and A2-mediated steady-state currents, but did not affect kainate- or N-methyl-D-aspartate (NMDA) receptor-mediated currents. Mouse hippocampal CA1 pyramidal neurons expressed CKAMP44 at low abundance, and overexpression of CKAMP44 led to stronger and faster AMPA receptor desensitization, slower recovery from desensitization, and a reduction in the paired-pulse ratio of AMPA currents. By contrast, dentate gyrus granule cells exhibited strong CKAMP44 expression, and CKAMP44 knockout increased the paired-pulse ratio of AMPA currents in lateral and medial perforant path-granule cell synapses. CKAMP44 thus modulates short-term plasticity at specific excitatory synapses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Engelhardt, Jakob -- Mack, Volker -- Sprengel, Rolf -- Kavenstock, Netta -- Li, Ka Wan -- Stern-Bach, Yael -- Smit, August B -- Seeburg, Peter H -- Monyer, Hannah -- New York, N.Y. -- Science. 2010 Mar 19;327(5972):1518-22. doi: 10.1126/science.1184178. Epub 2010 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Neurobiology, University of Heidelberg, 6910 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185686" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CA1 Region, Hippocampal/metabolism ; Calcium Channels/metabolism ; Dendritic Spines/metabolism ; Dentate Gyrus/cytology/*metabolism ; Excitatory Postsynaptic Potentials ; Glutamic Acid/metabolism ; Guanylate Kinase ; Intracellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Miniature Postsynaptic Potentials ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Neural Inhibition ; *Neuronal Plasticity ; Neurons/*metabolism ; Oocytes/metabolism ; Patch-Clamp Techniques ; Perforant Pathway ; Protein Interaction Domains and Motifs ; Protein Isoforms/genetics/metabolism ; Proteomics ; Pyramidal Cells/metabolism ; Receptors, AMPA/chemistry/*metabolism ; Recombinant Fusion Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Synapses/*physiology ; *Synaptic Transmission ; Xenopus laevis
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  • 88
    Publication Date: 2010-02-27
    Description: A20 negatively regulates inflammation by inhibiting the nuclear factor kappaB (NF-kappaB) transcription factor in the tumor necrosis factor-receptor (TNFR) and Toll-like receptor (TLR) pathways. A20 contains deubiquitinase and E3 ligase domains and thus has been proposed to function as a ubiquitin-editing enzyme downstream of TNFR1 by inactivating ubiquitinated RIP1. However, it remains unclear how A20 terminates NF-kappaB signaling downstream of TLRs. We have shown that A20 inhibited the E3 ligase activities of TRAF6, TRAF2, and cIAP1 by antagonizing interactions with the E2 ubiquitin conjugating enzymes Ubc13 and UbcH5c. A20, together with the regulatory molecule TAX1BP1, interacted with Ubc13 and UbcH5c and triggered their ubiquitination and proteasome-dependent degradation. These findings suggest mechanism of A20 action in the inhibition of inflammatory signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025292/" 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/PMC3025292/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shembade, Noula -- Ma, Averil -- Harhaj, Edward W -- R01 CA135362/CA/NCI NIH HHS/ -- R01 CA135362-04/CA/NCI NIH HHS/ -- R01 DK071939/DK/NIDDK NIH HHS/ -- R01 DK071939-07/DK/NIDDK NIH HHS/ -- R01 GM083143/GM/NIGMS NIH HHS/ -- R01 GM083143-03/GM/NIGMS NIH HHS/ -- R01CA135362/CA/NCI NIH HHS/ -- R01GM083143/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2010 Feb 26;327(5969):1135-9. doi: 10.1126/science.1182364.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA. nshembade@med.miami.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20185725" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Cells, Cultured ; Cysteine Endopeptidases/chemistry/genetics/*metabolism ; Gene Products, tax/metabolism ; Inflammation/*metabolism ; Inhibitor of Apoptosis Proteins/antagonists & inhibitors/metabolism ; Interleukin-1/immunology/metabolism ; Intracellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism ; Mice ; NF-kappa B/*metabolism ; Neoplasm Proteins/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Receptors, Tumor Necrosis Factor, Type I/metabolism ; *Signal Transduction ; TNF Receptor-Associated Factor 2/antagonists & inhibitors/metabolism ; TNF Receptor-Associated Factor 6/antagonists & inhibitors/metabolism ; Tumor Necrosis Factor-alpha/immunology/metabolism ; Ubiquitin-Conjugating Enzymes/*metabolism ; Ubiquitin-Protein Ligases/*antagonists & inhibitors/metabolism ; Ubiquitinated Proteins/metabolism ; Ubiquitination ; Zinc Fingers
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  • 89
    Publication Date: 2010-05-08
    Description: Clathrin-mediated endocytosis, the major pathway for ligand internalization into eukaryotic cells, is thought to be initiated by the clustering of clathrin and adaptors around receptors destined for internalization. However, here we report that the membrane-sculpting F-BAR domain-containing Fer/Cip4 homology domain-only proteins 1 and 2 (FCHo1/2) were required for plasma membrane clathrin-coated vesicle (CCV) budding and marked sites of CCV formation. Changes in FCHo1/2 expression levels correlated directly with numbers of CCV budding events, ligand endocytosis, and synaptic vesicle marker recycling. FCHo1/2 proteins bound specifically to the plasma membrane and recruited the scaffold proteins eps15 and intersectin, which in turn engaged the adaptor complex AP2. The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883440/" 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/PMC2883440/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henne, William Mike -- Boucrot, Emmanuel -- Meinecke, Michael -- Evergren, Emma -- Vallis, Yvonne -- Mittal, Rohit -- McMahon, Harvey T -- MC_U105178795/Medical Research Council/United Kingdom -- U.1051.02.007(78795)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Jun 4;328(5983):1281-4. doi: 10.1126/science.1188462. Epub 2010 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20448150" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex 2/metabolism ; Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport/metabolism ; Animals ; Calcium-Binding Proteins/metabolism ; Cell Line ; Cell Membrane/metabolism ; Cells, Cultured ; Clathrin/*metabolism ; Clathrin-Coated Vesicles/*metabolism ; *Endocytosis ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Membrane Proteins ; Mice ; Models, Molecular ; Neurons/cytology/metabolism ; Phosphoproteins/metabolism ; Protein Multimerization ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/metabolism ; Synaptic Vesicles/metabolism
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  • 90
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-08-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doms, Robert W -- New York, N.Y. -- Science. 2010 Aug 27;329(5995):1021-2. doi: 10.1126/science.1195116.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA. doms@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20798304" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/biosynthesis/*immunology ; Antibodies, Viral/biosynthesis/*immunology ; *Cross Protection ; Cross Reactions ; Ferrets ; Haplorhini ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology ; Humans ; Immunization Schedule ; Immunization, Secondary ; Influenza A Virus, H1N1 Subtype/*immunology ; Influenza A virus/*immunology ; Influenza Vaccines/*administration & dosage/*immunology ; Mice ; Vaccines, DNA/administration & dosage/immunology ; Vaccines, Inactivated/administration & dosage/immunology
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  • 91
    Publication Date: 2010-10-16
    Description: Neutrophils are recruited from the blood to sites of sterile inflammation, where they contribute to wound healing but may also cause tissue damage. By using spinning disk confocal intravital microscopy, we examined the kinetics and molecular mechanisms of neutrophil recruitment to sites of focal hepatic necrosis in vivo. Adenosine triphosphate released from necrotic cells activated the Nlrp3 inflammasome to generate an inflammatory microenvironment that alerted circulating neutrophils to adhere within liver sinusoids. Subsequently, generation of an intravascular chemokine gradient directed neutrophil migration through healthy tissue toward foci of damage. Lastly, formyl-peptide signals released from necrotic cells guided neutrophils through nonperfused sinusoids into the injury. Thus, dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonald, Braedon -- Pittman, Keir -- Menezes, Gustavo B -- Hirota, Simon A -- Slaba, Ingrid -- Waterhouse, Christopher C M -- Beck, Paul L -- Muruve, Daniel A -- Kubes, Paul -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):362-6. doi: 10.1126/science.1195491.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Research Group, University of Calgary, Alberta T2N 4N1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20947763" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Carrier Proteins/metabolism ; Cell Adhesion ; Chemokine CXCL2/metabolism ; Chemokines/metabolism ; Chemotaxis, Leukocyte ; Cues ; Endothelium, Vascular/physiology ; Inflammation/*immunology/metabolism/*pathology ; Kinetics ; Liver/blood supply/*immunology/metabolism/*pathology ; Liver Diseases/*immunology/metabolism/*pathology ; Macrophage-1 Antigen/physiology ; Mice ; Microscopy/methods ; Microscopy, Confocal ; Microvessels/physiology ; Necrosis ; *Neutrophil Infiltration ; Neutrophils/physiology ; Peptides/metabolism ; Receptors, Formyl Peptide/metabolism ; Receptors, Interleukin-8B/metabolism ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2X7 ; Signal Transduction
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  • 92
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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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  • 93
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smith, Andrew J -- Schwappach, Blanche -- New York, N.Y. -- Science. 2010 Jun 11;328(5984):1364-5. doi: 10.1126/science.1191529.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20538939" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chloride Channels/genetics/*metabolism ; Chlorides/*metabolism ; Endosomes/*metabolism ; Genetic Engineering ; Hydrogen-Ion Concentration ; Kidney Diseases/metabolism ; Lysosomes/*metabolism ; Membrane Potentials ; Mice ; *Protons
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  • 94
    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
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 95
    Publication Date: 2010-11-06
    Description: The stromal microenvironment of tumors, which is a mixture of hematopoietic and mesenchymal cells, suppresses immune control of tumor growth. A stromal cell type that was first identified in human cancers expresses fibroblast activation protein-alpha (FAP). We created a transgenic mouse in which FAP-expressing cells can be ablated. Depletion of FAP-expressing cells, which made up only 2% of all tumor cells in established Lewis lung carcinomas, caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumors by a process involving interferon-gamma and tumor necrosis factor-alpha. Depleting FAP-expressing cells in a subcutaneous model of pancreatic ductal adenocarcinoma also permitted immunological control of growth. Therefore, FAP-expressing cells are a nonredundant, immune-suppressive component of the tumor microenvironment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kraman, Matthew -- Bambrough, Paul J -- Arnold, James N -- Roberts, Edward W -- Magiera, Lukasz -- Jones, James O -- Gopinathan, Aarthi -- Tuveson, David A -- Fearon, Douglas T -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):827-30. doi: 10.1126/science.1195300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051638" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/immunology ; Cancer Vaccines/administration & dosage/immunology ; Carcinoma, Lewis Lung/*immunology/pathology/therapy ; Carcinoma, Pancreatic Ductal/*immunology/pathology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Survival ; Gelatinases/*metabolism ; *Immune Tolerance ; Interferon-gamma/immunology/metabolism ; Membrane Proteins/*metabolism ; Mice ; Mice, Transgenic ; Necrosis ; Neoplasm Transplantation ; Serine Endopeptidases/*metabolism ; Stromal Cells/*immunology/metabolism ; Tumor Microenvironment/*immunology ; Tumor Necrosis Factor-alpha/immunology/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
    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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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2010-03-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dorn, Gerald W 2nd -- R01 HL087871/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2010 Mar 26;327(5973):1586-7. doi: 10.1126/science.1188538.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. gdorn@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Compartmentation ; Cell Membrane/*metabolism/ultrastructure ; Cyclic AMP/*metabolism ; Heart Failure/*metabolism/pathology/physiopathology ; Humans ; Membrane Microdomains/metabolism ; Mice ; Myocardial Contraction ; Myocytes, Cardiac/*metabolism/ultrastructure ; Rats ; Receptors, Adrenergic, beta-1/*metabolism ; Receptors, Adrenergic, beta-2/*metabolism ; Sarcolemma/metabolism/ultrastructure ; Signal Transduction
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2010-03-27
    Description: Tumor manipulation of host immunity is important for tumor survival and invasion. Many cancers secrete CCL21, a chemoattractant for various leukocytes and lymphoid tissue inducer cells, which drive lymphoid neogenesis. CCL21 expression by melanoma tumors in mice was associated with an immunotolerant microenvironment, which included the induction of lymphoid-like reticular stromal networks, an altered cytokine milieu, and the recruitment of regulatory leukocyte populations. In contrast, CCL21-deficient tumors induced antigen-specific immunity. CCL21-mediated immune tolerance was dependent on host rather than tumor expression of the CCL21 receptor, CCR7, and could protect distant, coimplanted CCL21-deficient tumors and even nonsyngeneic allografts from rejection. We suggest that by altering the tumor microenvironment, CCL21-secreting tumors shift the host immune response from immunogenic to tolerogenic, which facilitates tumor progression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shields, Jacqueline D -- Kourtis, Iraklis C -- Tomei, Alice A -- Roberts, Joanna M -- Swartz, Melody A -- New York, N.Y. -- Science. 2010 May 7;328(5979):749-52. doi: 10.1126/science.1185837. Epub 2010 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20339029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line, Tumor ; Chemokine CCL21/*metabolism ; Cytokines/metabolism ; Disease Progression ; Female ; Immune Tolerance ; Lymph Nodes/immunology ; Lymphoid Tissue/*immunology/pathology ; Melanoma, Experimental/*immunology/*pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; RNA Interference ; Receptors, CCR7/metabolism ; Signal Transduction ; Stromal Cells/*immunology/pathology ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/immunology ; *Tumor Escape
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2010-06-05
    Description: In the classical form of alpha1-antitrypsin (AT) deficiency, a point mutation in AT alters the folding of a liver-derived secretory glycoprotein and renders it aggregation-prone. In addition to decreased serum concentrations of AT, the disorder is characterized by accumulation of the mutant alpha1-antitrypsin Z (ATZ) variant inside cells, causing hepatic fibrosis and/or carcinogenesis by a gain-of-toxic function mechanism. The proteasomal and autophagic pathways are known to mediate degradation of ATZ. Here we show that the autophagy-enhancing drug carbamazepine (CBZ) decreased the hepatic load of ATZ and hepatic fibrosis in a mouse model of AT deficiency-associated liver disease. These results provide a basis for testing CBZ, which has an extensive clinical safety profile, in patients with AT deficiency and also provide a proof of principle for therapeutic use of autophagy enhancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hidvegi, Tunda -- Ewing, Michael -- Hale, Pamela -- Dippold, Christine -- Beckett, Caroline -- Kemp, Carolyn -- Maurice, Nicholas -- Mukherjee, Amitava -- Goldbach, Christina -- Watkins, Simon -- Michalopoulos, George -- Perlmutter, David H -- DK076918/DK/NIDDK NIH HHS/ -- HL037784/HL/NHLBI NIH HHS/ -- R01 DK076918/DK/NIDDK NIH HHS/ -- R01 DK084512/DK/NIDDK NIH HHS/ -- RR022241/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2010 Jul 9;329(5988):229-32. doi: 10.1126/science.1190354. Epub 2010 Jun 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20522742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy/*drug effects ; Carbamazepine/administration & dosage/*pharmacology/therapeutic use ; Cell Line ; Disease Models, Animal ; Endoplasmic Reticulum/metabolism ; HeLa Cells ; Humans ; Liver/drug effects/*metabolism/pathology ; Liver Cirrhosis/*drug therapy/etiology/metabolism/pathology ; Mice ; Mice, Transgenic ; Mutant Proteins/chemistry/metabolism ; Phagosomes/drug effects/ultrastructure ; Phenotype ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding ; Solubility ; alpha 1-Antitrypsin/chemistry/genetics/*metabolism ; alpha 1-Antitrypsin Deficiency/complications/*metabolism/pathology
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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