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  • Mutation  (538)
  • American Association for the Advancement of Science (AAAS)  (538)
  • American Chemical Society (ACS)
  • Elsevier
  • Oxford University Press
  • 2005-2009  (538)
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  • American Association for the Advancement of Science (AAAS)  (538)
  • American Chemical Society (ACS)
  • Elsevier
  • Oxford University Press
  • Nature Publishing Group (NPG)  (55)
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  • 101
    Publication Date: 2008-03-01
    Description: Carbon dioxide (CO2) elicits different olfactory behaviors across species. In Drosophila, neurons that detect CO2 are located in the antenna, form connections in a ventral glomerulus in the antennal lobe, and mediate avoidance. By contrast, in the mosquito these neurons are in the maxillary palps (MPs), connect to medial sites, and promote attraction. We found in Drosophila that loss of a microRNA, miR-279, leads to formation of CO2 neurons in the MPs. miR-279 acts through down-regulation of the transcription factor Nerfin-1. The ectopic neurons are hybrid cells. They express CO2 receptors and form connections characteristic of CO2 neurons, while exhibiting wiring and receptor characteristics of MP olfactory receptor neurons (ORNs). We propose that this hybrid ORN reveals a cellular intermediate in the evolution of species-specific behaviors elicited by CO2.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714168/" 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/PMC2714168/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cayirlioglu, Pelin -- Kadow, Ilona Grunwald -- Zhan, Xiaoli -- Okamura, Katsutomo -- Suh, Greg S B -- Gunning, Dorian -- Lai, Eric C -- Zipursky, S Lawrence -- DC006485/DC/NIDCD NIH HHS/ -- R01 GM083300/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1256-60. doi: 10.1126/science.1149483.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18309086" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Animals, Genetically Modified ; Carbon Dioxide/*analysis/metabolism ; Drosophila/genetics/*physiology ; Drosophila Proteins/*genetics/metabolism ; Gene Expression Regulation ; Hybrid Cells/physiology ; MicroRNAs/genetics/*metabolism ; Mutation ; Olfactory Receptor Neurons/cytology/*physiology ; Receptors, Cell Surface/*metabolism ; Sense Organs/physiology ; Species Specificity ; Transcription Factors/*genetics/metabolism
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  • 102
    Publication Date: 2008-05-03
    Description: Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask: a recessive, chemically induced mutant mouse phenotype, characterized by progressive loss of body (but not facial) hair and microcytic anemia. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via proximal promoter element(s). TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430097/" 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/PMC2430097/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Du, Xin -- She, Ellen -- Gelbart, Terri -- Truksa, Jaroslav -- Lee, Pauline -- Xia, Yu -- Khovananth, Kevin -- Mudd, Suzanne -- Mann, Navjiwan -- Moresco, Eva Marie Y -- Beutler, Ernest -- Beutler, Bruce -- AI054523/AI/NIAID NIH HHS/ -- DK53505-09/DK/NIDDK NIH HHS/ -- R01 DK053505-09/DK/NIDDK NIH HHS/ -- U54 AI054523/AI/NIAID NIH HHS/ -- U54 AI054523-019005/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 May 23;320(5879):1088-92. doi: 10.1126/science.1157121. Epub 2008 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18451267" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Macrocytic/genetics/metabolism ; Animals ; Antimicrobial Cationic Peptides/*genetics/metabolism ; Cell Line, Tumor ; Gene Expression Regulation ; Hepcidins ; Humans ; Iron/blood/*deficiency/metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Models, Biological ; Mutation ; Phenotype ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Serine Endopeptidases/chemistry/genetics/*metabolism ; Signal Transduction ; Transfection
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  • 103
    Publication Date: 2008-12-06
    Description: During cytokinesis, the guanosine triphosphatase (GTPase) RhoA orchestrates contractile ring assembly and constriction. RhoA signaling is controlled by the central spindle, a set of microtubule bundles that forms between the separating chromosomes. Centralspindlin, a protein complex consisting of the kinesin-6 ZEN-4 and the Rho family GTPase activating protein (GAP) CYK-4, is required for central spindle assembly and cytokinesis in Caenorhabditis elegans. However, the importance of the CYK-4 GAP activity and whether it regulates RhoA remain unclear. We found that two separation-of-function mutations in the GAP domain of CYK-4 lead to cytokinesis defects that mimic centralspindlin loss of function. These defects could be rescued by depletion of the GTPase Rac or its effectors, but not by depletion of RhoA. Thus, inactivation of Rac by centralspindlin functions in parallel with RhoA activation to drive contractile ring constriction during cytokinesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736296/" 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/PMC2736296/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Canman, Julie C -- Lewellyn, Lindsay -- Laband, Kimberley -- Smerdon, Stephen J -- Desai, Arshad -- Bowerman, Bruce -- Oegema, Karen -- GM058017/GM/NIGMS NIH HHS/ -- MC_U117584228/Medical Research Council/United Kingdom -- R01 GM049869/GM/NIGMS NIH HHS/ -- R01 GM049869-15/GM/NIGMS NIH HHS/ -- R01 GM058017/GM/NIGMS NIH HHS/ -- T32 CA067754/CA/NCI NIH HHS/ -- T32 GM008666/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1543-6. doi: 10.1126/science.1163086.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Biology, University of Oregon, Eugene, OR 97403, USA. jcanman@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056985" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Caenorhabditis elegans/*cytology/embryology/genetics/*metabolism ; Caenorhabditis elegans Proteins/*antagonists & ; inhibitors/chemistry/genetics/*metabolism ; *Cytokinesis ; Embryo, Nonmammalian/cytology/metabolism ; GTPase-Activating Proteins/chemistry/genetics/metabolism ; Genes, Helminth ; Kinesin/metabolism ; Mutation ; Protein Structure, Tertiary ; Signal Transduction ; Spindle Apparatus/physiology/ultrastructure ; rac GTP-Binding Proteins/*antagonists & inhibitors/metabolism ; rhoA GTP-Binding Protein/metabolism
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  • 104
    Publication Date: 2008-07-19
    Description: Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (〉80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771549/" 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/PMC2771549/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koh, Kyunghee -- Joiner, William J -- Wu, Mark N -- Yue, Zhifeng -- Smith, Corinne J -- Sehgal, Amita -- AG017628/AG/NIA NIH HHS/ -- P01 AG017628/AG/NIA NIH HHS/ -- P01 AG017628-070004/AG/NIA NIH HHS/ -- R01 NS072431/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Jul 18;321(5887):372-6. doi: 10.1126/science.1155942.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635795" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Behavior, Animal ; Brain/metabolism ; Cell Membrane/metabolism ; DNA Transposable Elements ; Drosophila Proteins/chemistry/*genetics/*physiology ; Drosophila melanogaster/genetics/*physiology ; Female ; *Genes, Insect ; Glycosylphosphatidylinositols ; Homeostasis ; Longevity ; Male ; Membrane Proteins/chemistry/*genetics/*physiology ; *Models, Animal ; Molecular Sequence Data ; Mutation ; Phenotype ; Shaker Superfamily of Potassium Channels/physiology ; Signal Transduction ; *Sleep/genetics/physiology ; Sleep Deprivation ; Transgenes
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  • 105
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-08-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holmes, Nick -- New York, N.Y. -- Science. 2008 Aug 1;321(5889):646-7. doi: 10.1126/science.1162294.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Pathology, Cambridge University, Cambridge CB2 1QP, UK. nh106@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18669848" target="_blank"〉PubMed〈/a〉
    Keywords: *Alternative Splicing ; Animals ; Antigens, CD45/chemistry/*genetics/metabolism ; CD4-Positive T-Lymphocytes/*immunology/*metabolism ; Heterogeneous-Nuclear Ribonucleoproteins/*metabolism ; Humans ; *Lymphocyte Activation ; Mice ; Mutation ; Platelet Membrane Glycoprotein IIb/genetics/metabolism ; Polymorphism, Single Nucleotide ; Protein Isoforms/chemistry/genetics/metabolism ; RNA Precursors/genetics ; STAT5 Transcription Factor/genetics/metabolism
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  • 106
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2008 Jul 11;321(5886):196-7. doi: 10.1126/science.321.5886.196.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18621652" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; *Biological Evolution ; Body Patterning ; DNA/chemistry/genetics ; Developmental Biology ; Environment ; Epigenesis, Genetic ; Gene Expression Regulation ; Genetics ; Genetics, Population ; Genomics ; Mutation ; Selection, Genetic
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  • 107
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Charlesworth, Deborah -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1484-5. doi: 10.1126/science.1167573.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK. deborah.charlesworth@ed.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056969" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; *Biological Evolution ; Centromere/*physiology ; Chromosomes, Plant/*physiology ; Crosses, Genetic ; Gene Frequency ; Genetic Markers ; Heterozygote ; Hybridization, Genetic ; Meiosis ; Mimulus/*genetics/physiology ; Models, Genetic ; Mutation ; Selection, Genetic
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  • 108
    Publication Date: 2008-09-06
    Description: Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658639/" 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/PMC2658639/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prabhakar, Shyam -- Visel, Axel -- Akiyama, Jennifer A -- Shoukry, Malak -- Lewis, Keith D -- Holt, Amy -- Plajzer-Frick, Ingrid -- Morrison, Harris -- Fitzpatrick, David R -- Afzal, Veena -- Pennacchio, Len A -- Rubin, Edward M -- Noonan, James P -- 1-F32-GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367/GM/NIGMS NIH HHS/ -- F32 GM074367-02/GM/NIGMS NIH HHS/ -- HG003988/HG/NHGRI NIH HHS/ -- HL066681/HL/NHLBI NIH HHS/ -- MC_U127561093/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1346-50. doi: 10.1126/science.1159974.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Body Patterning/*genetics ; Conserved Sequence ; Embryonic Development ; *Enhancer Elements, Genetic ; Evolution, Molecular ; Extremities/*embryology ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Humans ; Limb Buds/embryology/metabolism ; Macaca mulatta/genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; PAX9 Transcription Factor/metabolism ; Pan troglodytes/genetics ; Selection, Genetic ; Transcription Factors/metabolism
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  • 109
    Publication Date: 2008-05-10
    Description: Temperature pervasively affects all cellular processes. In response to a rapid increase in temperature, all cells undergo a heat shock response, an ancient and highly conserved program of stress-inducible gene expression, to reestablish cellular homeostasis. In isolated cells, the heat shock response is initiated by the presence of misfolded proteins and therefore thought to be cell-autonomous. In contrast, we show that within the metazoan Caenorhabditis elegans, the heat shock response of somatic cells is not cell-autonomous but rather depends on the thermosensory neuron, AFD, which senses ambient temperature and regulates temperature-dependent behavior. We propose a model whereby this loss of cell autonomy serves to integrate behavioral, metabolic, and stress-related responses to establish an organismal response to environmental change.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429343/" 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/PMC3429343/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prahlad, Veena -- Cornelius, Tyler -- Morimoto, Richard I -- R01 AG026647/AG/NIA NIH HHS/ -- R01 AG026647-01/AG/NIA NIH HHS/ -- R01 AG026647-02/AG/NIA NIH HHS/ -- R01 AG026647-03/AG/NIA NIH HHS/ -- R01 AG026647-04/AG/NIA NIH HHS/ -- R01 GM038109/GM/NIGMS NIH HHS/ -- R37 GM038109/GM/NIGMS NIH HHS/ -- R37 GM038109-19/GM/NIGMS NIH HHS/ -- R37 GM038109-20/GM/NIGMS NIH HHS/ -- R37 GM038109-21/GM/NIGMS NIH HHS/ -- R37 GM038109-22/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 May 9;320(5877):811-4. doi: 10.1126/science.1156093.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18467592" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/cytology/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Genes, Helminth ; Heat-Shock Proteins/genetics/physiology ; Heat-Shock Response/genetics/*physiology ; Models, Neurological ; Mutation ; Neurons, Afferent/*physiology ; Pheromones/physiology ; Protein Folding ; Thermosensing/*physiology ; Transcription Factors/genetics/physiology
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  • 110
    Publication Date: 2008-08-23
    Description: Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756290/" 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/PMC2756290/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Horwitz, Gregory A -- Zhang, Kangling -- McBrian, Matthew A -- Grunstein, Michael -- Kurdistani, Siavash K -- Berk, Arnold J -- CA25235/CA/NCI NIH HHS/ -- R37 CA025235/CA/NCI NIH HHS/ -- R37 CA025235-30/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1084-5. doi: 10.1126/science.1155544.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719283" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Adenovirus E1A Proteins/genetics/*metabolism ; Adenoviruses, Human/*metabolism ; Antigens, Polyomavirus Transforming/metabolism ; CREB-Binding Protein/metabolism ; *Cell Cycle ; Cell Line ; Cell Transformation, Viral ; Cells, Cultured ; HeLa Cells ; Histones/*metabolism ; Humans ; Lysine/metabolism ; Mutation ; p300-CBP Transcription Factors/metabolism
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  • 111
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-09-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wray, Gregory A -- Babbitt, Courtney C -- New York, N.Y. -- Science. 2008 Sep 5;321(5894):1300-1. doi: 10.1126/science.1163568.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Institute for Genome Science and Policy, Duke University, Box 90338, Durham, NC 27708, USA. gwray@duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18772422" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Chromatin Immunoprecipitation ; Computational Biology ; Conserved Sequence ; Drosophila Proteins/metabolism ; *Enhancer Elements, Genetic ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Humans ; Introns ; Mutation ; Nuclear Proteins/metabolism ; Oligonucleotide Array Sequence Analysis ; Phosphoproteins/metabolism ; *Regulatory Sequences, Nucleic Acid ; Transcription Factors/metabolism
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  • 112
    Publication Date: 2008-12-06
    Description: The concerted movement of cells from different germ layers contributes to morphogenesis during early embryonic development. Using an optimized imaging approach and quantitative methods, we analyzed the trajectories of hundreds of ectodermal cells and internalized mesodermal cells within Drosophila embryos over 2 hours during gastrulation. We found a high level of cellular organization, with mesoderm cell movements correlating with some but not all ectoderm movements. During migration, the mesoderm population underwent two ordered waves of cell division and synchronous cell intercalation, and cells at the leading edge stably maintained position. Fibroblast growth factor (FGF) signaling guides mesodermal cell migration; however, we found some directed dorsal migration in an FGF receptor mutant, which suggests that additional signals are involved. Thus, decomposing complex cellular movements can provide detailed insights into collective cell migration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801059/" 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/PMC2801059/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMahon, Amy -- Supatto, Willy -- Fraser, Scott E -- Stathopoulos, Angelike -- P50 HG004071/HG/NHGRI NIH HHS/ -- R01 GM078542/GM/NIGMS NIH HHS/ -- R01 GM078542-02/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1546-50. doi: 10.1126/science.1167094.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056986" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; *Cell Movement ; Drosophila/*embryology/genetics/metabolism ; Ectoderm/*cytology ; Embryo, Nonmammalian/*cytology ; Fibroblast Growth Factors/metabolism ; *Gastrulation ; Mesoderm/*cytology ; Morphogenesis ; Mutation ; Phenotype ; Signal Transduction
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  • 113
    Publication Date: 2008-08-23
    Description: Adenovirus e1a induces quiescent human cells to replicate. We found that e1a causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and p107) and p300/CBP histone acetyltransferases on promoters, the effect of which is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set of genes, thereby stimulating cell cycling and inhibiting antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to promoters of cell cycle and growth genes, causing enrichment of p300/CBP, PCAF (p300/CBP-associated factor), and H3K18ac; depletion of RB proteins; and transcriptional activation. e1a also associates transiently with promoters of antiviral genes, causing enrichment for RB, p130, and H4K16ac; increased nucleosome density; and transcriptional repression. At later times, e1a and p107 bind mainly to promoters of development and differentiation genes, repressing transcription. The temporal order of e1a binding requires its interactions with p300/CBP and RB proteins. Our data uncover a defined epigenetic reprogramming leading to cellular transformation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693122/" 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/PMC2693122/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferrari, Roberto -- Pellegrini, Matteo -- Horwitz, Gregory A -- Xie, Wei -- Berk, Arnold J -- Kurdistani, Siavash K -- CA25235/CA/NCI NIH HHS/ -- R37 CA025235/CA/NCI NIH HHS/ -- R37 CA025235-30/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1086-8. doi: 10.1126/science.1155546.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719284" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/genetics/*metabolism ; Adenoviruses, Human/genetics/*metabolism ; CREB-Binding Protein/metabolism ; Cell Transformation, Viral ; Crk-Associated Substrate Protein/genetics/metabolism ; *Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation ; Histones/metabolism ; Humans ; Mutation ; Promoter Regions, Genetic ; Protein Binding ; RNA, Messenger/genetics/metabolism ; Retinoblastoma Protein/genetics/metabolism ; Retinoblastoma-Like Protein p107/genetics/metabolism ; Transcription, Genetic ; p300-CBP Transcription Factors/metabolism
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  • 114
    Publication Date: 2008-10-25
    Description: Heterochromatin formation at fission yeast centromeres is directed by RNA interference (RNAi). Noncoding transcripts derived from centromeric repeats are processed into small interfering RNAs (siRNAs) that direct the RNA-induced transcriptional silencing (RITS) effector complex to engage centromere transcripts, resulting in recruitment of the histone H3 lysine 9 methyltransferase Clr4, and hence silencing. We have found that defects in specific splicing factors, but not splicing itself, affect the generation of centromeric siRNAs and consequently centromeric heterochromatin integrity. Moreover, splicing factors physically associate with Cid12, a component of the RNAi machinery, and with centromeric chromatin, consistent with a direct role in RNAi. We propose that spliceosomal complexes provide a platform for siRNA generation and hence facilitate effective centromere repeat silencing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585287/" 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/PMC2585287/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bayne, Elizabeth H -- Portoso, Manuela -- Kagansky, Alexander -- Kos-Braun, Isabelle C -- Urano, Takeshi -- Ekwall, Karl -- Alves, Flavia -- Rappsilber, Juri -- Allshire, Robin C -- 065061/Wellcome Trust/United Kingdom -- 065061/Z/Wellcome Trust/United Kingdom -- 067844/Wellcome Trust/United Kingdom -- G0301153/Medical Research Council/United Kingdom -- G0301153/ID:69173/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2008 Oct 24;322(5901):602-6. doi: 10.1126/science.1164029.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, 6.34 Swann Building, Edinburgh EH9 3JR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18948543" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics/metabolism ; Centromere/*genetics/metabolism ; Genes, Fungal ; Heterochromatin/metabolism ; Histones/metabolism ; Methylation ; Mutation ; Phosphoproteins/genetics/metabolism ; *RNA Interference ; *RNA Splicing ; RNA, Small Interfering/*metabolism ; Ribonucleoprotein, U2 Small Nuclear/genetics/metabolism ; Schizosaccharomyces/*genetics/metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; Spliceosomes/metabolism
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  • 115
    Publication Date: 2008-04-05
    Description: Mutations in mitochondrial DNA (mtDNA) occur at high frequency in human tumors, but whether these mutations alter tumor cell behavior has been unclear. We used cytoplasmic hybrid (cybrid) technology to replace the endogenous mtDNA in a mouse tumor cell line that was poorly metastatic with mtDNA from a cell line that was highly metastatic, and vice versa. Using assays of metastasis in mice, we found that the recipient tumor cells acquired the metastatic potential of the transferred mtDNA. The mtDNA conferring high metastatic potential contained G13997A and 13885insC mutations in the gene encoding NADH (reduced form of nicotinamide adenine dinucleotide) dehydrogenase subunit 6 (ND6). These mutations produced a deficiency in respiratory complex I activity and were associated with overproduction of reactive oxygen species (ROS). Pretreatment of the highly metastatic tumor cells with ROS scavengers suppressed their metastatic potential in mice. These results indicate that mtDNA mutations can contribute to tumor progression by enhancing the metastatic potential of tumor cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ishikawa, Kaori -- Takenaga, Keizo -- Akimoto, Miho -- Koshikawa, Nobuko -- Yamaguchi, Aya -- Imanishi, Hirotake -- Nakada, Kazuto -- Honma, Yoshio -- Hayashi, Jun-Ichi -- New York, N.Y. -- Science. 2008 May 2;320(5876):661-4. doi: 10.1126/science.1156906. Epub 2008 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18388260" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcysteine/pharmacology ; Animals ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; *DNA, Mitochondrial ; *DNA, Neoplasm ; Electron Transport Complex I/genetics/metabolism ; Free Radical Scavengers/pharmacology ; HeLa Cells ; Humans ; Hybrid Cells ; Mice ; Mutation ; NADH Dehydrogenase/*genetics/metabolism ; Neoplasm Metastasis/*genetics ; Reactive Oxygen Species/*metabolism
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  • 116
    Publication Date: 2008-11-01
    Description: Fuller et al. (Reports, 23 May 2008, p. 1074) reported that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food-entrained circadian rhythms. We report that mice bearing a null mutation of Bmal1 exhibit normal food-anticipatory circadian rhythms. Lack of food anticipation in Bmal1-/- mice reported by Fuller et al. may reflect morbidity due to weight loss, thus raising questions about their conclusions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583785/" 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/PMC2583785/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mistlberger, Ralph E -- Yamazaki, Shin -- Pendergast, Julie S -- Landry, Glenn J -- Takumi, Toru -- Nakamura, Wataru -- NS051278/NS/NINDS NIH HHS/ -- R01 NS051278/NS/NINDS NIH HHS/ -- R01 NS051278-04/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):675; author reply 675. doi: 10.1126/science.1161284.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada. mistlber@sfu.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974333" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Behavior, Animal ; Biological Clocks/*physiology ; Circadian Rhythm/*physiology ; Cues ; Darkness ; Dorsomedial Hypothalamic Nucleus/*metabolism ; *Food ; *Light ; Mice ; Mutation
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  • 117
    Publication Date: 2008-06-07
    Description: Telomeres are specialized chromatin structures that protect chromosomal ends. Protection of telomeres 1 (Pot1) binds to the telomeric G-rich overhang, thereby protecting telomeres and regulating telomerase. Mammalian POT1 and TPP1 interact and constitute part of the six-protein shelterin complex. Here we report that Tpz1, the TPP1 homolog in fission yeast, forms a complex with Pot1. Tpz1 binds to Ccq1 and the previously undiscovered protein Poz1 (Pot1-associated in Schizosaccharomyces pombe), which protect telomeres redundantly and regulate telomerase in positive and negative manners, respectively. Thus, the Pot1-Tpz1 complex accomplishes its functions by recruiting effector molecules Ccq1 and Poz1. Moreover, Poz1 bridges Pot1-Tpz1 and Taz1-Rap1, thereby connecting the single-stranded and double-stranded telomeric DNA regions. Such molecular architectures are similar to those of mammalian shelterin, indicating that the overall DNA-protein architecture is conserved across evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyoshi, Tomoichiro -- Kanoh, Junko -- Saito, Motoki -- Ishikawa, Fuyuki -- New York, N.Y. -- Science. 2008 Jun 6;320(5881):1341-4. doi: 10.1126/science.1154819.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18535244" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Carrier Proteins/chemistry/genetics/*metabolism ; Chromatin Immunoprecipitation ; DNA, Fungal/metabolism ; Immunoprecipitation ; Molecular Sequence Data ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; Schizosaccharomyces/genetics/*metabolism ; Schizosaccharomyces pombe Proteins/chemistry/genetics/*metabolism ; Telomerase/metabolism ; Telomere/metabolism/*physiology/ultrastructure ; Telomere-Binding Proteins/chemistry/genetics/*metabolism ; Two-Hybrid System Techniques
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  • 118
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice, William R -- Friberg, Urban -- New York, N.Y. -- Science. 2008 Jan 4;319(5859):42-3. doi: 10.1126/science.1153482.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA. rice@lifesci.ucsb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18174425" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Drosophila melanogaster/*genetics ; Female ; *Gene Expression Regulation ; Gene Silencing ; Genes, Insect ; Male ; Mutation ; Selection, Genetic ; Y Chromosome/*genetics
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  • 119
    Publication Date: 2008-02-16
    Description: F1-adenosine triphosphatase (ATPase) is an ATP-driven rotary molecular motor in which the central gamma subunit rotates inside a cylinder made of three alpha and three beta subunits alternately arranged. The rotor shaft, an antiparallel alpha-helical coiled coil of the amino and carboxyl termini of the gamma subunit, deeply penetrates the central cavity of the stator cylinder. We truncated the shaft step by step until the remaining rotor head would be outside the cavity and simply sat on the concave entrance of the stator orifice. All truncation mutants rotated in the correct direction, implying torque generation, although the average rotary speeds were low and short mutants exhibited moments of irregular motion. Neither a fixed pivot nor a rigid axle was needed for rotation of F1-ATPase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Furuike, Shou -- Hossain, Mohammad Delawar -- Maki, Yasushi -- Adachi, Kengo -- Suzuki, Toshiharu -- Kohori, Ayako -- Itoh, Hiroyasu -- Yoshida, Masasuke -- Kinosita, Kazuhiko Jr -- New York, N.Y. -- Science. 2008 Feb 15;319(5865):955-8. doi: 10.1126/science.1151343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Faculty of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18276891" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Hydrolysis ; Microspheres ; Molecular Motor Proteins/*chemistry/metabolism ; Molecular Sequence Data ; Mutant Proteins/chemistry ; Mutation ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Proton-Translocating ATPases/*chemistry/genetics/*metabolism ; Rotation ; Torque
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  • 120
    Publication Date: 2008-08-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharjee, Yudhijit -- Enserink, Martin -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1027. doi: 10.1126/science.321.5892.1027.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719255" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax ; Bacillus anthracis/*genetics ; *Bioterrorism ; *Forensic Genetics ; Humans ; Law Enforcement ; Mutation ; Spores, Bacterial/genetics ; United States ; United States Government Agencies
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  • 121
    Publication Date: 2008-04-12
    Description: Execution of motor behaviors relies on circuitries effectively integrating immediate sensory feedback to efferent pathways controlling muscle activity. It remains unclear how, during neuromuscular circuit assembly, sensory and motor projections become incorporated into tightly coordinated, yet functionally separate pathways. We report that, within axial nerves, establishment of discrete afferent and efferent pathways depends on coordinate signaling between coextending sensory and motor projections. These heterotypic axon-axon interactions require motor axonal EphA3/EphA4 receptor tyrosine kinases activated by cognate sensory axonal ephrin-A ligands. Genetic elimination of trans-axonal ephrin-A --〉 EphA signaling in mice triggers drastic motor-sensory miswiring, culminating in functional efferents within proximal afferent pathways. Effective assembly of a key circuit underlying motor behaviors thus critically depends on trans-axonal signaling interactions resolving motor and sensory projections into discrete pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158657/" 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/PMC3158657/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallarda, Benjamin W -- Bonanomi, Dario -- Muller, Daniel -- Brown, Arthur -- Alaynick, William A -- Andrews, Shane E -- Lemke, Greg -- Pfaff, Samuel L -- Marquardt, Till -- NS031249-14A1/NS/NINDS NIH HHS/ -- NS054172-01A2/NS/NINDS NIH HHS/ -- R01 NS054172/NS/NINDS NIH HHS/ -- R01 NS054172-01A2/NS/NINDS NIH HHS/ -- R01 NS054172-02/NS/NINDS NIH HHS/ -- R01 NS054172-03/NS/NINDS NIH HHS/ -- R01 NS054172-04/NS/NINDS NIH HHS/ -- R01 NS054172-05/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2008 Apr 11;320(5873):233-6. doi: 10.1126/science.1153758.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18403711" target="_blank"〉PubMed〈/a〉
    Keywords: Afferent Pathways/physiology ; Animals ; Axons/*physiology ; Cells, Cultured ; Coculture Techniques ; Efferent Pathways/physiology ; Electrophysiology ; Ephrins/*metabolism ; Ganglia, Spinal/cytology/physiology ; Growth Cones/physiology ; Ligands ; Mice ; Mice, Transgenic ; Motor Activity ; Motor Neurons/*physiology ; Muscle, Skeletal/innervation ; Mutation ; Neurons, Afferent/*physiology ; Peripheral Nerves/cytology/physiology ; Receptor, EphA3/genetics/*metabolism ; Receptor, EphA4/genetics/*metabolism ; Signal Transduction
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  • 122
    Publication Date: 2008-09-20
    Description: A large body of evidence indicates that metazoan innate immunity is regulated by the nervous system, but the mechanisms involved in the process and the biological importance of such control remain unclear. We show that a neural circuit involving npr-1, which encodes a G protein-coupled receptor (GPCR) related to mammalian neuropeptide Y receptors, functions to suppress innate immune responses. The immune inhibitory function requires a guanosine 3',5'-monophosphate-gated ion channel encoded by tax-2 and tax-4 as well as the soluble guanylate cyclase GCY-35. Furthermore, we show that npr-1- and gcy-35-expressing sensory neurons actively suppress immune responses of nonneuronal tissues. A full-genome microarray analysis on animals with altered neural function due to mutation in npr-1 shows an enrichment in genes that are markers of innate immune responses, including those regulated by a conserved PMK-1/p38 mitogen-activated protein kinase signaling pathway. These results present evidence that neurons directly control innate immunity in C. elegans, suggesting that GPCRs may participate in neural circuits that receive inputs from either pathogens or infected sites and integrate them to coordinate appropriate immune responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831475/" 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/PMC2831475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Styer, Katie L -- Singh, Varsha -- Macosko, Evan -- Steele, Sarah E -- Bargmann, Cornelia I -- Aballay, Alejandro -- GM070977/GM/NIGMS NIH HHS/ -- R01 GM070977/GM/NIGMS NIH HHS/ -- R01 GM070977-01A1/GM/NIGMS NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):460-4. doi: 10.1126/science.1163673. Epub 2008 Sep 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, 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/18801967" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*immunology/microbiology/physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Enterococcus faecalis/immunology/pathogenicity ; Gene Expression Regulation ; Genes, Helminth ; Guanylate Cyclase/genetics/metabolism ; *Immunity, Innate ; Ion Channels/genetics/metabolism ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Mutation ; Nerve Net/physiology ; Neurons, Afferent/*metabolism ; Oligonucleotide Array Sequence Analysis ; Oxygen/physiology ; Pseudomonas aeruginosa/immunology/pathogenicity ; Receptors, Neuropeptide Y/genetics/*metabolism ; Salmonella enterica/immunology/pathogenicity
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  • 123
    Publication Date: 2008-06-28
    Description: As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific "codon pair bias" provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over-or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of protein translation, and polioviruses containing such amino acid-independent changes were attenuated in mice. Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This "death by a thousand cuts" strategy could be generally applicable to attenuating many kinds of viruses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754401/" 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/PMC2754401/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coleman, J Robert -- Papamichail, Dimitris -- Skiena, Steven -- Futcher, Bruce -- Wimmer, Eckard -- Mueller, Steffen -- AI075219/AI/NIAID NIH HHS/ -- AI15122/AI/NIAID NIH HHS/ -- R01 AI075219/AI/NIAID NIH HHS/ -- R01 AI075219-01A1/AI/NIAID NIH HHS/ -- R37 AI015122/AI/NIAID NIH HHS/ -- R37 AI015122-34/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 Jun 27;320(5884):1784-7. doi: 10.1126/science.1155761.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18583614" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Antibodies, Viral/biosynthesis ; Capsid Proteins/*genetics ; Cloning, Molecular ; *Codon ; Cytopathogenic Effect, Viral ; *Genome, Viral ; HeLa Cells ; Hot Temperature ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Poliomyelitis/immunology/virology ; Poliovirus/*genetics/growth & development/immunology/*pathogenicity ; *Poliovirus Vaccines/genetics/immunology ; Protein Biosynthesis ; Vaccination ; Vaccines, Attenuated/genetics/immunology ; Viral Plaque Assay ; Virulence
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  • 124
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-05-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Birchler, James A -- Kavi, Harsh H -- New York, N.Y. -- Science. 2008 May 23;320(5879):1023-4. doi: 10.1126/science.1159018. Epub 2008 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biological Sciences, University of Missouri, Columbia, MO 65211, USA. birchlerj@missouri.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18467555" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; DNA Transposable Elements ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*genetics/metabolism ; Eukaryotic Initiation Factor-2/metabolism ; Eukaryotic Initiation Factors ; Germ Cells/metabolism ; Mice ; MicroRNAs/genetics/metabolism ; Mutation ; RNA Helicases/genetics/metabolism ; RNA Interference ; RNA, Small Interfering/*genetics/*metabolism ; RNA-Induced Silencing Complex/genetics/metabolism ; Ribonuclease III/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 125
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sutcliffe, James S -- New York, N.Y. -- Science. 2008 Jul 11;321(5886):208-9. doi: 10.1126/science.1160555.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-8548, USA. james.s.sutcliffe@vanderbilt.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18621658" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/etiology/*genetics/physiopathology ; Brain/growth & development/physiology ; Chromosome Aberrations ; *Chromosome Mapping ; Consanguinity ; Gene Deletion ; Gene Dosage ; Gene Duplication ; Gene Expression Regulation ; *Genetic Predisposition to Disease ; Homozygote ; Humans ; Mutation ; Oligonucleotide Array Sequence Analysis ; Pedigree ; Sodium-Hydrogen Antiporter/genetics ; Synapses/physiology
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  • 126
    Publication Date: 2008-06-21
    Description: Biofilms are multicellular aggregates of sessile bacteria encased by an extracellular matrix and are important medically as a source of drug-resistant microbes. In Bacillus subtilis, we found that an operon required for biofilm matrix biosynthesis also encoded an inhibitor of motility, EpsE. EpsE arrested flagellar rotation in a manner similar to that of a clutch, by disengaging motor force-generating elements in cells embedded in the biofilm matrix. The clutch is a simple, rapid, and potentially reversible form of motility control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blair, Kris M -- Turner, Linda -- Winkelman, Jared T -- Berg, Howard C -- Kearns, Daniel B -- AI065540/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 Jun 20;320(5883):1636-8. doi: 10.1126/science.1157877.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Indiana University, Bloomington, IN 47405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18566286" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus subtilis/genetics/*physiology ; Bacterial Proteins/chemistry/genetics/metabolism/*physiology ; Biofilms/*growth & development ; Flagella/*physiology ; Genes, Bacterial ; Molecular Motor Proteins/genetics/*physiology ; Molecular Sequence Data ; Movement ; Mutation ; Operon ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism
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  • 127
    Publication Date: 2008-07-26
    Description: Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward. This requires the replication fork-associated acetyl transferase Eco1, but Eco1's mechanism of action is not known. We identified spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast. An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion. A second set of eco1-1 suppressors inactivate the budding yeast ortholog of the cohesin destabilizer Wapl. Our results indicate that Eco1 modifies cohesin to stabilize sister chromatid cohesion in parallel with a cohesion establishment reaction that is in principle Eco1-independent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rolef Ben-Shahar, Tom -- Heeger, Sebastian -- Lehane, Chris -- East, Philip -- Flynn, Helen -- Skehel, Mark -- Uhlmann, Frank -- New York, N.Y. -- Science. 2008 Jul 25;321(5888):563-6. doi: 10.1126/science.1157774.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln'sInn Fields, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18653893" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/chemistry/genetics/*metabolism ; Alleles ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Chondroitin Sulfate Proteoglycans/chemistry/genetics/*metabolism ; Chromatids/*physiology ; Chromosomal Proteins, Non-Histone/chemistry/genetics/*metabolism ; Chromosomes, Fungal/*physiology ; DNA Repair ; DNA Replication ; DNA, Fungal/metabolism ; Mutation ; Nuclear Proteins/chemistry/genetics/*metabolism ; Protein Subunits/chemistry/genetics/metabolism ; S Phase ; Saccharomyces cerevisiae/genetics/growth & development/*physiology ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Suppression, Genetic
    Print ISSN: 0036-8075
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  • 128
    Publication Date: 2008-07-19
    Description: Changes in redox status have been observed during immune responses in different organisms, but the associated signaling mechanisms are poorly understood. In plants, these redox changes regulate the conformation of NPR1, a master regulator of salicylic acid (SA)-mediated defense genes. NPR1 is sequestered in the cytoplasm as an oligomer through intermolecular disulfide bonds. We report that S-nitrosylation of NPR1 by S-nitrosoglutathione (GSNO) at cysteine-156 facilitates its oligomerization, which maintains protein homeostasis upon SA induction. Conversely, the SA-induced NPR1 oligomer-to-monomer reaction is catalyzed by thioredoxins (TRXs). Mutations in both NPR1 cysteine-156 and TRX compromised NPR1-mediated disease resistance. Thus, the regulation of NPR1 is through the opposing action of GSNO and TRX. These findings suggest a link between pathogen-triggered redox changes and gene regulation in plant immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833675/" 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/PMC3833675/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tada, Yasuomi -- Spoel, Steven H -- Pajerowska-Mukhtar, Karolina -- Mou, Zhonglin -- Song, Junqi -- Wang, Chun -- Zuo, Jianru -- Dong, Xinnian -- 1R01-GM69594/GM/NIGMS NIH HHS/ -- R01 GM069594/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 15;321(5891):952-6. doi: 10.1126/science.1156970. Epub 2008 Jul 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Post Office Box 90338, Duke University, Durham, NC 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635760" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/chemistry/*immunology/*metabolism/microbiology ; Arabidopsis Proteins/*chemistry/genetics/metabolism ; Cysteine/metabolism ; Gene Expression Regulation, Plant ; Homeostasis ; Immunity, Innate ; Mutation ; Nitric Oxide/metabolism ; Oxidation-Reduction ; Plant Diseases/*immunology ; Protein Conformation ; Protein Structure, Quaternary ; Pseudomonas syringae/immunology ; Recombinant Fusion Proteins/chemistry/metabolism ; S-Nitrosoglutathione/*metabolism/pharmacology ; Salicylic Acid/metabolism/pharmacology ; Thioredoxin h/*metabolism
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  • 129
    Publication Date: 2008-01-19
    Description: The evolutionarily conserved Wnt/Wingless signal transduction pathway directs cell proliferation, cell fate, and cell death during development in metazoans and is inappropriately activated in several types of cancer. The majority of colorectal carcinomas contain truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor, a negative regulator of Wnt/Wingless signaling. Here, we demonstrate that Drosophila Apc homologs also have an activating role in both physiological and ectopic Wingless signaling. The Apc amino terminus is important for its activating function, whereas the beta-catenin binding sites are dispensable. Apc likely promotes Wingless transduction through down-regulation of Axin, a negative regulator of Wingless signaling. Given the evolutionary conservation of APC in Wnt signal transduction, an activating role may also be present in vertebrates with relevance to development and cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takacs, Carter M -- Baird, Jason R -- Hughes, Edward G -- Kent, Sierra S -- Benchabane, Hassina -- Paik, Raehum -- Ahmed, Yashi -- KO8CA078532/CA/NCI NIH HHS/ -- R01 CA105038/CA/NCI NIH HHS/ -- R01CA105038/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Jan 18;319(5861):333-6. doi: 10.1126/science.1151232.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and the Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03755, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18202290" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis ; Armadillo Domain Proteins/metabolism ; Axin Protein ; Binding Sites ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; Down-Regulation ; Drosophila/genetics/growth & development/*metabolism ; Drosophila Proteins/chemistry/genetics/*metabolism ; Genes, Insect ; Mutation ; Photoreceptor Cells, Invertebrate/cytology ; Proto-Oncogene Proteins/*metabolism ; *Signal Transduction ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/chemistry/genetics/*metabolism ; Wings, Animal/growth & development/metabolism ; Wnt1 Protein
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  • 130
    Publication Date: 2008-12-20
    Description: Selection pressure exerted by insects and microorganisms shapes the diversity of plant secondary metabolites. We identified a metabolic pathway for glucosinolates, known insect deterrents, that differs from the pathway activated by chewing insects. This pathway is active in living plant cells, may contribute to glucosinolate turnover, and has been recruited for broad-spectrum antifungal defense responses. The Arabidopsis CYP81F2 gene encodes a P450 monooxygenase that is essential for the pathogen-induced accumulation of 4-methoxyindol-3-ylmethylglucosinolate, which in turn is activated by the atypical PEN2 myrosinase (a type of beta-thioglucoside glucohydrolase) for antifungal defense. We propose that reiterated enzymatic cycles, controlling the generation of toxic molecules and their detoxification, enable the recruitment of glucosinolates in defense responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bednarek, Pawel -- Pislewska-Bednarek, Mariola -- Svatos, Ales -- Schneider, Bernd -- Doubsky, Jan -- Mansurova, Madina -- Humphry, Matt -- Consonni, Chiara -- Panstruga, Ralph -- Sanchez-Vallet, Andrea -- Molina, Antonio -- Schulze-Lefert, Paul -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):101-6. doi: 10.1126/science.1163732. Epub 2008 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Microbe Interactions, Max Planck Institut fur Zuchtungsforschung, Carl-von-Linne-Weg 10, D-50829 Koln, Germany. bednarek@mpiz-koeln.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19095900" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics/immunology/*metabolism/*microbiology ; Arabidopsis Proteins/genetics/*metabolism ; Ascomycota/growth & development/*pathogenicity ; Cysteine/metabolism ; Cytochrome P-450 Enzyme System/genetics/metabolism ; Genes, Plant ; Glucosinolates/*metabolism ; Glycoside Hydrolases/genetics/metabolism ; Indoles/*metabolism ; Metabolic Networks and Pathways ; Mutation ; N-Glycosyl Hydrolases/genetics/*metabolism ; Plant Diseases/immunology/*microbiology ; Thiazoles/metabolism ; Thiones/metabolism ; Tryptophan/metabolism
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  • 131
    Publication Date: 2008-12-17
    Description: Sphingosine-1-phosphate (S1P) is a secreted lipid mediator that functions in vascular development; however, it remains unclear how S1P secretion is regulated during embryogenesis. We identified a zebrafish mutant, ko157, that displays cardia bifida (two hearts) resembling that in the S1P receptor-2 mutant. A migration defect of myocardial precursors in the ko157 mutant is due to a mutation in a multipass transmembrane protein, Spns2, and can be rescued by S1P injection. We show that the export of S1P from cells requires Spns2. spns2 is expressed in the extraembryonic tissue yolk syncytial layer (YSL), and the introduction of spns2 mRNA in the YSL restored the cardiac defect in the ko157 mutant. Thus, Spns2 in the YSL functions as a S1P transporter in S1P secretion, thereby regulating myocardial precursor migration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawahara, Atsuo -- Nishi, Tsuyoshi -- Hisano, Yu -- Fukui, Hajime -- Yamaguchi, Akihito -- Mochizuki, Naoki -- New York, N.Y. -- Science. 2009 Jan 23;323(5913):524-7. doi: 10.1126/science.1167449. Epub 2008 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Analysis, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan. atsuo@ri.ncvc.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074308" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Blastomeres/metabolism ; CHO Cells ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Movement ; Cricetinae ; Cricetulus ; Embryo, Nonmammalian/cytology/*metabolism ; Embryonic Development ; Heart/*embryology ; Heart Defects, Congenital/embryology ; Humans ; Lysophospholipids/*metabolism ; Membrane Proteins/chemistry/genetics/*metabolism ; Mesoderm/metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Oligonucleotides, Antisense ; Organogenesis ; Signal Transduction ; Somites/embryology/metabolism ; Sphingosine/*analogs & derivatives/metabolism ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/chemistry/genetics/*metabolism
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  • 132
    Publication Date: 2008-12-17
    Description: Might DNA sequence variation reflect germline genetic activity and underlying chromatin structure? We investigated this question using medaka (Japanese killifish, Oryzias latipes), by comparing the genomic sequences of two strains (Hd-rR and HNI) and by mapping approximately 37.3 million nucleosome cores from Hd-rR blastulae and 11,654 representative transcription start sites from six embryonic stages. We observed a distinctive approximately 200-base pair (bp) periodic pattern of genetic variation downstream of transcription start sites; the rate of insertions and deletions longer than 1 bp peaked at positions of approximately +200, +400, and +600 bp, whereas the point mutation rate showed corresponding valleys. This approximately 200-bp periodicity was correlated with the chromatin structure, with nucleosome occupancy minimized at positions 0, +200, +400, and +600 bp. These data exemplify the potential for genetic activity (transcription) and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757552/" 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/PMC2757552/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasaki, Shin -- Mello, Cecilia C -- Shimada, Atsuko -- Nakatani, Yoichiro -- Hashimoto, Shin-Ichi -- Ogawa, Masako -- Matsushima, Kouji -- Gu, Sam Guoping -- Kasahara, Masahiro -- Ahsan, Budrul -- Sasaki, Atsushi -- Saito, Taro -- Suzuki, Yutaka -- Sugano, Sumio -- Kohara, Yuji -- Takeda, Hiroyuki -- Fire, Andrew -- Morishita, Shinichi -- R01 GM037706/GM/NIGMS NIH HHS/ -- R01 GM037706-24/GM/NIGMS NIH HHS/ -- R01 GM37706/GM/NIGMS NIH HHS/ -- T32 CA009151/CA/NCI NIH HHS/ -- T32 CA09151/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 16;323(5912):401-4. doi: 10.1126/science.1163183. Epub 2008 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, 277-0882, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19074313" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Base Sequence ; Chromatin/*physiology/ultrastructure ; DNA/chemistry/*genetics ; DNA Repair ; *Genetic Variation ; Genome ; INDEL Mutation ; Mutagenesis ; Mutation ; Nucleosomes/*physiology/ultrastructure ; Oryzias/embryology/*genetics ; Point Mutation ; Promoter Regions, Genetic ; *Transcription Initiation Site ; Transcription, Genetic
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  • 133
    Publication Date: 2008-05-24
    Description: The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. We find that the Rag proteins--a family of four related small guanosine triphosphatases (GTPases)--interact with mTORC1 in an amino acid-sensitive manner and are necessary for the activation of the mTORC1 pathway by amino acids. A Rag mutant that is constitutively bound to guanosine triphosphate interacted strongly with mTORC1, and its expression within cells made the mTORC1 pathway resistant to amino acid deprivation. Conversely, expression of a guanosine diphosphate-bound Rag mutant prevented stimulation of mTORC1 by amino acids. The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2475333/" 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/PMC2475333/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sancak, Yasemin -- Peterson, Timothy R -- Shaul, Yoav D -- Lindquist, Robert A -- Thoreen, Carson C -- Bar-Peled, Liron -- Sabatini, David M -- AI47389/AI/NIAID NIH HHS/ -- R01 AI047389/AI/NIAID NIH HHS/ -- R01 AI047389-09/AI/NIAID NIH HHS/ -- R01 CA103866/CA/NCI NIH HHS/ -- R01 CA103866-05/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Jun 13;320(5882):1496-501. doi: 10.1126/science.1157535. Epub 2008 May 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology (MIT), Nine Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18497260" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Amino Acids/*metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dimerization ; Guanosine Triphosphate/metabolism ; Humans ; Insulin/metabolism ; Leucine/metabolism ; Monomeric GTP-Binding Proteins/genetics/*metabolism ; Multiprotein Complexes ; Mutant Proteins/metabolism ; Mutation ; Neuropeptides/metabolism ; Phosphorylation ; Protein Binding ; Protein Kinases/metabolism ; Proteins/*metabolism ; *Signal Transduction ; TOR Serine-Threonine Kinases ; Transcription Factors/*metabolism
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  • 134
    Publication Date: 2008-07-26
    Description: Chromosome segregation, transcriptional regulation, and repair of DNA double-strand breaks require the cohesin protein complex. Cohesin holds the replicated chromosomes (sister chromatids) together to mediate sister chromatid cohesion. The mechanism of how cohesion is established is unknown. We found that in budding yeast, the head domain of the Smc3p subunit of cohesin is acetylated by the Eco1p acetyltransferase at two evolutionarily conserved residues, promoting the chromatin-bound cohesin to tether sister chromatids. Smc3p acetylation is induced in S phase after the chromatin loading of cohesin and is suppressed in G(1) and G(2)/M. Smc3 head acetylation and its cell cycle regulation provide important insights into the biology and mechanism of cohesion establishment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Unal, Elcin -- Heidinger-Pauli, Jill M -- Kim, Woong -- Guacci, Vincent -- Onn, Itay -- Gygi, Steven P -- Koshland, Douglas E -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Jul 25;321(5888):566-9. doi: 10.1126/science.1157880.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18653894" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/genetics/*metabolism ; Amino Acid Sequence ; Amino Acid Substitution ; Cell Cycle Proteins/chemistry/genetics/*metabolism ; Cell Division ; Chondroitin Sulfate Proteoglycans/chemistry/genetics/*metabolism ; Chromatids/*physiology ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/genetics/*metabolism ; Chromosomes, Fungal/*physiology ; G1 Phase ; G2 Phase ; Immunoprecipitation ; Lysine/metabolism ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Protein Structure, Tertiary ; S Phase ; Saccharomyces cerevisiae/genetics/growth & development/*physiology ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
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  • 135
    Publication Date: 2008-10-11
    Description: A long-standing goal of biology is to map the behavior of all cells during vertebrate embryogenesis. We developed digital scanned laser light sheet fluorescence microscopy and recorded nuclei localization and movement in entire wild-type and mutant zebrafish embryos over the first 24 hours of development. Multiview in vivo imaging at 1.5 billion voxels per minute provides "digital embryos," that is, comprehensive databases of cell positions, divisions, and migratory tracks. Our analysis of global cell division patterns reveals a maternally defined initial morphodynamic symmetry break, which identifies the embryonic body axis. We further derive a model of germ layer formation and show that the mesendoderm forms from one-third of the embryo's cells in a single event. Our digital embryos, with 55 million nucleus entries, are provided as a resource.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keller, Philipp J -- Schmidt, Annette D -- Wittbrodt, Joachim -- Stelzer, Ernst H K -- New York, N.Y. -- Science. 2008 Nov 14;322(5904):1065-9. doi: 10.1126/science.1162493. Epub 2008 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany. keller@embl.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18845710" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Body Patterning ; *Cell Division ; Cell Nucleus/physiology ; Databases, Factual ; Embryo, Nonmammalian/*cytology ; *Embryonic Development ; Endoderm/embryology ; Germ Layers/cytology/*embryology/physiology ; Image Processing, Computer-Assisted ; Mesoderm/embryology ; Microscopy, Fluorescence/methods ; Models, Biological ; Motion Pictures as Topic ; Mutation ; Software ; Zebrafish/*embryology/genetics ; beta Catenin/analysis
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 136
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-02-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delaval, Benedicte -- Doxsey, Stephen -- New York, N.Y. -- Science. 2008 Feb 8;319(5864):732-3. doi: 10.1126/science.1154513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. stephen.doxsey@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18258883" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens/*genetics/*physiology ; Cell Death ; Centrosome/*physiology ; DNA Damage ; Dwarfism/*genetics/pathology/physiopathology ; Humans ; Microcephaly/*genetics/pathology/physiopathology ; Microtubule-Associated Proteins/genetics/physiology ; *Mitosis ; Mutation ; Phenotype ; Spindle Apparatus/physiology ; Syndrome
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  • 137
    Publication Date: 2008-05-17
    Description: High complementarity between plant microRNAs (miRNAs) and their messenger RNA targets is thought to cause silencing, prevalently by endonucleolytic cleavage. We have isolated Arabidopsis mutants defective in miRNA action. Their analysis provides evidence that plant miRNA-guided silencing has a widespread translational inhibitory component that is genetically separable from endonucleolytic cleavage. We further show that the same is true of silencing mediated by small interfering RNA (siRNA) populations. Translational repression is effected in part by the ARGONAUTE proteins AGO1 and AGO10. It also requires the activity of the microtubule-severing enzyme katanin, implicating cytoskeleton dynamics in miRNA action, as recently suggested from animal studies. Also as in animals, the decapping component VARICOSE (VCS)/Ge-1 is required for translational repression by miRNAs, which suggests that the underlying mechanisms in the two kingdoms are related.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brodersen, Peter -- Sakvarelidze-Achard, Lali -- Bruun-Rasmussen, Marianne -- Dunoyer, Patrice -- Yamamoto, Yoshiharu Y -- Sieburth, Leslie -- Voinnet, Olivier -- New York, N.Y. -- Science. 2008 May 30;320(5880):1185-90. doi: 10.1126/science.1159151. Epub 2008 May 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Biologie Moleculaire des Plantes du CNRS, Unite Propre de Recherche 2357, 12 rue du General Zimmer, 67084 Strasbourg Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18483398" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics/physiology ; Arabidopsis/genetics/physiology ; Arabidopsis Proteins/genetics/physiology ; Argonaute Proteins ; *Gene Expression Regulation, Plant ; Green Fluorescent Proteins/genetics ; MicroRNAs/*physiology ; Mutation ; Protein Biosynthesis ; RNA Caps ; *RNA Interference ; RNA, Plant/*physiology ; RNA, Small Interfering/*physiology
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  • 138
    Publication Date: 2008-03-08
    Description: Of all types of DNA damage, DNA double-strand breaks (DSBs) pose the greatest challenge to cells. One might have, therefore, anticipated that a sizable number of DNA DSBs would be incompatible with cell proliferation. Yet recent experimental findings suggest that, in both precancerous lesions and cancers, activated oncogenes induce stalling and collapse of DNA replication forks, which in turn leads to formation of DNA DSBs. This continuous formation of DNA DSBs may contribute to the genomic instability that characterizes the vast majority of human cancers. In addition, in precancerous lesions, these DNA DSBs activate p53, which, by inducing apoptosis or senescence, raises a barrier to tumor progression. Breach of this barrier by various mechanisms, most notably by p53 mutations, that impair the DNA damage response pathway allows cancers to develop. Thus, oncogene-induced DNA damage may explain two key features of cancer: genomic instability and the high frequency of p53 mutations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Halazonetis, Thanos D -- Gorgoulis, Vassilis G -- Bartek, Jiri -- New York, N.Y. -- Science. 2008 Mar 7;319(5868):1352-5. doi: 10.1126/science.1140735.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205 Geneva, Switzerland. Thanos.Halazonetis@molbio.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18323444" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Proliferation ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA Replication ; Disease Progression ; Genes, p53 ; Genomic Instability ; Humans ; Models, Biological ; Mutation ; Neoplasms/*genetics/pathology/physiopathology ; *Oncogenes ; Precancerous Conditions/*genetics/pathology/physiopathology ; Tumor Suppressor Protein p53/metabolism
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  • 139
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-02-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Viscidi, Raphael P -- Shah, Keerti V -- New York, N.Y. -- Science. 2008 Feb 22;319(5866):1049-50. doi: 10.1126/science.1155048.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. rviscid1@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18292327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Polyomavirus Transforming/genetics ; Carcinoma, Merkel Cell/*virology ; Cell Transformation, Viral ; Genome, Viral ; Humans ; Mutation ; Phylogeny ; Polyomavirus/classification/*genetics/isolation & purification/pathogenicity ; Polyomavirus Infections/*virology ; Skin Neoplasms/*virology ; Tumor Virus Infections/*virology ; Virus Integration
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  • 140
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-04-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alberts, Bruce -- New York, N.Y. -- Science. 2008 Apr 4;320(5872):19. doi: 10.1126/science.1158084.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18388262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; *Biomedical Research ; *DNA Repair ; Humans ; Mutation ; *Neoplasms/genetics/pathology/therapy
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  • 141
    Publication Date: 2008-04-26
    Description: Little is known about the way developmental cues affect how cells interpret their environment. We characterized the transcriptional response to high salinity of different cell layers and developmental stages of the Arabidopsis root and found that transcriptional responses are highly constrained by developmental parameters. These transcriptional changes lead to the differential regulation of specific biological functions in subsets of cell layers, several of which correspond to observable physiological changes. We showed that known stress pathways primarily control semiubiquitous responses and used mutants that disrupt epidermal patterning to reveal cell-layer-specific and inter-cell-layer effects. By performing a similar analysis using iron deprivation, we identified common cell-type-specific stress responses and revealed the crucial role the environment plays in defining the transcriptional outcome of cell-fate decisions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dinneny, Jose R -- Long, Terri A -- Wang, Jean Y -- Jung, Jee W -- Mace, Daniel -- Pointer, Solomon -- Barron, Christa -- Brady, Siobhan M -- Schiefelbein, John -- Benfey, Philip N -- New York, N.Y. -- Science. 2008 May 16;320(5878):942-5. doi: 10.1126/science.1153795. Epub 2008 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Duke University, Durham, NC 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18436742" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/metabolism ; Algorithms ; Arabidopsis/*cytology/genetics/*physiology ; Arabidopsis Proteins/genetics/metabolism ; Culture Media ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Genes, Plant ; Iron/metabolism ; Mutation ; Plant Epidermis/cytology/genetics/physiology ; Plant Roots/*cytology/genetics/growth & development/*physiology ; Promoter Regions, Genetic ; Response Elements ; *Salinity ; Transcription Factors/metabolism ; Transcription, Genetic
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  • 142
    Publication Date: 2008-09-20
    Description: FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian beta-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haydon, David J -- Stokes, Neil R -- Ure, Rebecca -- Galbraith, Greta -- Bennett, James M -- Brown, David R -- Baker, Patrick J -- Barynin, Vladimir V -- Rice, David W -- Sedelnikova, Sveta E -- Heal, Jonathan R -- Sheridan, Joseph M -- Aiwale, Sachin T -- Chauhan, Pramod K -- Srivastava, Anil -- Taneja, Amit -- Collins, Ian -- Errington, Jeff -- Czaplewski, Lloyd G -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2008 Sep 19;321(5896):1673-5. doi: 10.1126/science.1159961.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Prolysis, Begbroke Science Park, Oxfordshire OX5 1PF, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18801997" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacillus subtilis/chemistry/*drug effects/genetics ; Bacterial Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; Binding Sites ; Cell Division/drug effects ; Crystallography, X-Ray ; Cytoskeletal Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; Drug Resistance, Bacterial/genetics ; Drug Resistance, Multiple, Bacterial ; Ligands ; Methicillin Resistance ; Mice ; Microbial Sensitivity Tests ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Pyridines/chemistry/metabolism/*pharmacology/therapeutic use ; Staphylococcal Infections/*drug therapy ; Staphylococcus aureus/chemistry/*drug effects ; Thiazoles/chemistry/metabolism/*pharmacology/therapeutic use ; Tubulin/chemistry/metabolism
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  • 143
    Publication Date: 2008-10-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2008 Oct 10;322(5899):176. doi: 10.1126/science.322.5899.176.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18845717" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryo, Nonmammalian/*cytology/embryology/physiology ; *Embryonic Development ; Mesoderm/cytology/growth & development ; Microscopy/instrumentation/*methods ; *Motion Pictures as Topic ; Mutation ; Zebrafish/*embryology/genetics
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  • 144
    Publication Date: 2008-10-04
    Description: The protein modifier ubiquitin is a signal for proteasome-mediated degradation in eukaryotes. Proteasome-bearing prokaryotes have been thought to degrade proteins via a ubiquitin-independent pathway. We have identified a prokaryotic ubiquitin-like protein, Pup (Rv2111c), which was specifically conjugated to proteasome substrates in the pathogen Mycobacterium tuberculosis. Pupylation occurred on lysines and required proteasome accessory factor A (PafA). In a pafA mutant, pupylated proteins were absent and substrates accumulated, thereby connecting pupylation with degradation. Although analogous to ubiquitylation, pupylation appears to proceed by a different chemistry. Thus, like eukaryotes, bacteria may use a small-protein modifier to control protein stability.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698935/" 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/PMC2698935/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pearce, Michael J -- Mintseris, Julian -- Ferreyra, Jessica -- Gygi, Steven P -- Darwin, K Heran -- 5T32AI07189-25/AI/NIAID NIH HHS/ -- AI065437/AI/NIAID NIH HHS/ -- GM67945/GM/NIGMS NIH HHS/ -- HG3456/HG/NHGRI NIH HHS/ -- HG3616/HG/NHGRI NIH HHS/ -- HL092774/HL/NHLBI NIH HHS/ -- R01 HL092774/HL/NHLBI NIH HHS/ -- R01 HL092774-01/HL/NHLBI NIH HHS/ -- R01 HL092774-02/HL/NHLBI NIH HHS/ -- R56 AI065437/AI/NIAID NIH HHS/ -- R56 AI065437-01A2/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 Nov 14;322(5904):1104-7. doi: 10.1126/science.1163885. Epub 2008 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18832610" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/genetics/*metabolism ; Amino Acid Motifs ; Bacterial Proteins/chemistry/genetics/isolation & purification/*metabolism ; Glutamic Acid/metabolism ; Glutamine/metabolism ; Glycine/metabolism ; Lysine/metabolism ; Mass Spectrometry ; Molecular Sequence Data ; Mutation ; Mycobacterium smegmatis/metabolism ; Mycobacterium tuberculosis/genetics/*metabolism ; Proteasome Endopeptidase Complex/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Ubiquitination ; Ubiquitins/chemistry/genetics/isolation & purification/*metabolism
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  • 145
    Publication Date: 2008-09-13
    Description: The enzyme mTOR (mammalian target of rapamycin) is a major target for therapeutic intervention to treat many human diseases, including cancer, but very little is known about the processes that control levels of mTOR protein. Here, we show that mTOR is targeted for ubiquitination and consequent degradation by binding to the tumor suppressor protein FBXW7. Human breast cancer cell lines and primary tumors showed a reciprocal relation between loss of FBXW7 and deletion or mutation of PTEN (phosphatase and tensin homolog), which also activates mTOR. Tumor cell lines harboring deletions or mutations in FBXW7 are particularly sensitive to rapamycin treatment, which suggests that loss of FBXW7 may be a biomarker for human cancers susceptible to treatment with inhibitors of the mTOR pathway.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849753/" 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/PMC2849753/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mao, Jian-Hua -- Kim, Il-Jin -- Wu, Di -- Climent, Joan -- Kang, Hio Chung -- DelRosario, Reyno -- Balmain, Allan -- R01 CA116481/CA/NCI NIH HHS/ -- U01 CA084244/CA/NCI NIH HHS/ -- U01 CA084244-08/CA/NCI NIH HHS/ -- U01 CA084244-09/CA/NCI NIH HHS/ -- U01 CA084244-10/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2008 Sep 12;321(5895):1499-502. doi: 10.1126/science.1162981.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Institute, University of California at San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18787170" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/drug therapy/genetics/*metabolism/pathology ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; F-Box Proteins/genetics/*metabolism ; Gene Deletion ; Gene Dosage ; Gene Silencing ; Genes, Tumor Suppressor ; Humans ; Mice ; Mice, Nude ; Mutation ; Neoplasm Transplantation ; PTEN Phosphohydrolase/genetics/*metabolism ; Phosphorylation ; Protein Binding ; Protein Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Sirolimus/pharmacology/therapeutic use ; TOR Serine-Threonine Kinases ; Transfection ; Tumor Suppressor Proteins/*metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination
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  • 146
    Publication Date: 2008-04-05
    Description: The full promise of human genomics will be realized only when the genomes of thousands of individuals can be sequenced for comparative analysis. A reference sequence enables the use of short read length. We report an amplification-free method for determining the nucleotide sequence of more than 280,000 individual DNA molecules simultaneously. A DNA polymerase adds labeled nucleotides to surface-immobilized primer-template duplexes in stepwise fashion, and the asynchronous growth of individual DNA molecules was monitored by fluorescence imaging. Read lengths of 〉25 bases and equivalent phred software program quality scores approaching 30 were achieved. We used this method to sequence the M13 virus to an average depth of 〉150x and with 100% coverage; thus, we resequenced the M13 genome with high-sensitivity mutation detection. This demonstrates a strategy for high-throughput low-cost resequencing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harris, Timothy D -- Buzby, Phillip R -- Babcock, Hazen -- Beer, Eric -- Bowers, Jayson -- Braslavsky, Ido -- Causey, Marie -- Colonell, Jennifer -- Dimeo, James -- Efcavitch, J William -- Giladi, Eldar -- Gill, Jaime -- Healy, John -- Jarosz, Mirna -- Lapen, Dan -- Moulton, Keith -- Quake, Stephen R -- Steinmann, Kathleen -- Thayer, Edward -- Tyurina, Anastasia -- Ward, Rebecca -- Weiss, Howard -- Xie, Zheng -- R01 HG004144-01/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Apr 4;320(5872):106-9. doi: 10.1126/science.1150427.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Helicos BioSciences Corporation, One Kendall Square, Cambridge, MA 02139, USA. tharris@helicosbio.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18388294" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Bacteriophage M13/*genetics ; Computational Biology/methods ; DNA Primers ; DNA, Viral/chemistry/*genetics ; *Genome, Viral ; Mutation ; Sequence Alignment ; Sequence Analysis, DNA/*methods ; Software ; Templates, Genetic
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  • 147
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-07-19
    Description: The large majority of antibiotics currently used for treating infections and the antibiotic resistance genes acquired by human pathogens each have an environmental origin. Recent work indicates that the function of these elements in their environmental reservoirs may be very distinct from the "weapon-shield" role they play in clinical settings. Changes in natural ecosystems, including the release of large amounts of antimicrobials, might alter the population dynamics of microorganisms, including selection of resistance, with consequences for human health that are difficult to predict.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martinez, Jose L -- New York, N.Y. -- Science. 2008 Jul 18;321(5887):365-7. doi: 10.1126/science.1159483.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia (CSIC), Darwin 3, Campus UAM, Cantoblanco, 28049-Madrid, and CIBERESP, Spain. jlmtnez@cnb.csic.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18635792" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/*metabolism/*pharmacology/therapeutic use ; Bacteria/*drug effects/genetics/metabolism ; Bacterial Infections/drug therapy/microbiology ; Drug Resistance, Bacterial/*genetics ; Drug Resistance, Multiple, Bacterial/*genetics ; *Ecosystem ; Evolution, Molecular ; Gene Transfer, Horizontal ; *Genes, Bacterial ; Humans ; Mutation ; Soil Microbiology
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  • 148
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2008 Dec 5;322(5907):1454-5. doi: 10.1126/science.322.5907.1454.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056949" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Clinical Trials as Topic ; Dystrophin/biosynthesis/*genetics ; *Exons ; *Genetic Therapy ; Humans ; Mice ; Muscle Cells/metabolism/pathology ; Muscles/metabolism/pathology/physiopathology ; Muscular Dystrophy, Duchenne/genetics/metabolism/pathology/*therapy ; Mutation ; Oligodeoxyribonucleotides, Antisense/genetics/*therapeutic use
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  • 149
    Publication Date: 2008-08-30
    Description: How ion channels are gated to regulate ion flux in and out of cells is the subject of intense interest. The Escherichia coli mechanosensitive channel, MscS, opens to allow rapid ion efflux, relieving the turgor pressure that would otherwise destroy the cell. We present a 3.45 angstrom-resolution structure for the MscS channel in an open conformation. This structure has a pore diameter of approximately 13 angstroms created by substantial rotational rearrangement of the three transmembrane helices. The structure suggests a molecular mechanism that underlies MscS gating and its decay of conductivity during prolonged activation. Support for this mechanism is provided by single-channel analysis of mutants with altered gating characteristics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299565/" 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/PMC3299565/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Wenjian -- Black, Susan S -- Edwards, Michelle D -- Miller, Samantha -- Morrison, Emma L -- Bartlett, Wendy -- Dong, Changjiang -- Naismith, James H -- Booth, Ian R -- 040174/Wellcome Trust/United Kingdom -- 077564/Wellcome Trust/United Kingdom -- BB/F003455/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0400277/Medical Research Council/United Kingdom -- G0400277(70731)/Medical Research Council/United Kingdom -- GR077564MA/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2008 Aug 29;321(5893):1179-83. doi: 10.1126/science.1159262.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Biomolecular Sciences, The North Haugh, University of St. Andrews, KY16 9ST, Scotland, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18755969" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Membrane/*chemistry ; Crystallography, X-Ray ; Electric Conductivity ; Escherichia coli/*chemistry/physiology ; Escherichia coli Proteins/*chemistry/genetics/*physiology ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Ion Channels/*chemistry/genetics/*physiology ; Models, Molecular ; Mutant Proteins/chemistry ; Mutation ; Patch-Clamp Techniques ; Pressure ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 150
    Publication Date: 2008-11-22
    Description: Every organ depends on blood vessels for oxygen and nutrients, but the vasculature associated with individual organs can be structurally and molecularly diverse. The central nervous system (CNS) vasculature consists of a tightly sealed endothelium that forms the blood-brain barrier, whereas blood vessels of other organs are more porous. Wnt7a and Wnt7b encode two Wnt ligands produced by the neuroepithelium of the developing CNS coincident with vascular invasion. Using genetic mouse models, we found that these ligands directly target the vascular endothelium and that the CNS uses the canonical Wnt signaling pathway to promote formation and CNS-specific differentiation of the organ's vasculature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stenman, Jan M -- Rajagopal, Jay -- Carroll, Thomas J -- Ishibashi, Makoto -- McMahon, Jill -- McMahon, Andrew P -- DK054364/DK/NIDDK NIH HHS/ -- HL076393/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2008 Nov 21;322(5905):1247-50. doi: 10.1126/science.1164594.〈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/19023080" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood-Brain Barrier/*embryology ; Central Nervous System/*blood supply/*embryology ; Embryonic Induction ; Mice ; Mutation ; *Neovascularization, Physiologic ; Neuroepithelial Cells/physiology ; Proto-Oncogene Proteins/genetics/*physiology ; *Signal Transduction ; Wnt Proteins/genetics/*physiology ; beta Catenin/physiology
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  • 151
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-11-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hernando, Eva -- New York, N.Y. -- Science. 2008 Oct 31;322(5902):692-3. doi: 10.1126/science.1166151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. eva.hernando@med.nyu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18974340" target="_blank"〉PubMed〈/a〉
    Keywords: *Aneuploidy ; Animals ; Cell Line ; Cell Movement ; Cell Proliferation ; Cell Survival ; *Cell Transformation, Neoplastic ; Cells, Cultured ; Gene Amplification ; Genomic Instability ; Humans ; Mice ; Models, Biological ; Mutation ; Neoplasms/*genetics ; *Trisomy
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  • 152
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-03-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Armitage, Bruce A -- Berget, Peter B -- New York, N.Y. -- Science. 2008 Feb 29;319(5867):1195-6. doi: 10.1126/science.1155093.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Molecular Biosensor and Imaging Center (MBIC), Carnegie Mellon University, Pittsburgh, PA 15213, USA. army@cmu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18309067" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Antibodies, Monoclonal/*chemistry/genetics ; Antigen-Antibody Complex ; Binding Sites, Antibody ; Crystallization ; Fluorescence ; Fluorescent Dyes ; Hydrophobic and Hydrophilic Interactions ; Luminescence ; Molecular Structure ; Mutation ; Protein Conformation ; Spectrometry, Fluorescence ; Stilbenes/*chemistry/immunology ; Structure-Activity Relationship
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  • 153
    Publication Date: 2008-06-07
    Description: The role that natural selection plays in governing the locations and early evolution of copy-number mutations remains largely unexplored. We used high-density full-genome tiling arrays to create a fine-scale genomic map of copy-number polymorphisms (CNPs) in Drosophila melanogaster. We inferred a total of 2658 independent CNPs, 56% of which overlap genes. These include CNPs that are likely to be under positive selection, most notably high-frequency duplications encompassing toxin-response genes. The locations and frequencies of CNPs are strongly shaped by purifying selection, with deletions under stronger purifying selection than duplications. Among duplications, those overlapping exons or introns, as well as those falling on the X chromosome, seem to be subject to stronger purifying selection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Emerson, J J -- Cardoso-Moreira, Margarida -- Borevitz, Justin O -- Long, Manyuan -- New York, N.Y. -- Science. 2008 Jun 20;320(5883):1629-31. doi: 10.1126/science.1158078. Epub 2008 Jun 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA. jje@uchicago.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18535209" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA/genetics ; DNA, Intergenic ; Drosophila melanogaster/*genetics ; Exons ; Female ; *Gene Dosage ; Gene Duplication ; Gene Frequency ; Genes, Insect ; *Genome, Insect ; Introns ; Male ; Mutation ; Oligonucleotide Array Sequence Analysis ; *Polymorphism, Genetic ; *Selection, Genetic ; Sequence Deletion ; X Chromosome/genetics
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  • 154
    Publication Date: 2008-08-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enserink, Martin -- New York, N.Y. -- Science. 2008 Aug 15;321(5891):898-9. doi: 10.1126/science.321.5891.898.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18703714" target="_blank"〉PubMed〈/a〉
    Keywords: *Anthrax ; Bacillus anthracis/*genetics ; *Bioterrorism ; DNA Fingerprinting ; *Forensic Genetics ; *Genome, Bacterial ; Humans ; Mutation ; *Sequence Analysis, DNA ; Spores, Bacterial
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  • 155
    Publication Date: 2008-06-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enserink, Martin -- New York, N.Y. -- Science. 2008 Jun 27;320(5884):1709. doi: 10.1126/science.320.5884.1709a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18583587" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Capsid Proteins/*genetics ; Codon/*genetics ; Mice ; Mutation ; Poliomyelitis/immunology/prevention & control ; Poliovirus/*genetics/physiology ; *Poliovirus Vaccines/genetics/immunology ; Vaccines, Attenuated ; Vaccines, Inactivated/genetics/immunology ; Viral Vaccines/genetics/immunology
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  • 156
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-11-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2008 Nov 7;322(5903):839. doi: 10.1126/science.322.5903.839a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18988817" target="_blank"〉PubMed〈/a〉
    Keywords: Bioethical Issues ; Brain/growth & development ; Continental Population Groups/*genetics ; Genetic Variation ; *Genetics, Medical ; *Genomics ; Humans ; Information Dissemination ; Mutation ; Public Opinion ; Selection, Genetic ; Terminology as Topic
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  • 157
    Publication Date: 2008-11-15
    Description: Stomata, epidermal structures that modulate gas exchange between plants and the atmosphere, play critical roles in primary productivity and the global climate. Positively acting transcription factors and negatively acting mitogen-activated protein kinase (MAPK) signaling control stomatal development in Arabidopsis; however, it is not known how the opposing activities of these regulators are integrated. We found that a unique domain in a basic helix-loop-helix (bHLH) stomatal initiating factor, SPEECHLESS, renders it a MAPK phosphorylation target in vitro and modulates its function in vivo. MAPK cascades modulate a diverse set of activities including development, cell proliferation, and response to external stresses. The coupling of MAPK signaling to SPEECHLESS activity provides cell type specificity for MAPK output while allowing the integration of multiple developmental and environmental signals into the production and spacing of stomata.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lampard, Gregory R -- Macalister, Cora A -- Bergmann, Dominique C -- New York, N.Y. -- Science. 2008 Nov 14;322(5904):1113-6. doi: 10.1126/science.1162263.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19008449" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Basic Helix-Loop-Helix Transcription Factors/chemistry/genetics/*metabolism ; Cell Division ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/*metabolism ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Plant Epidermis/cytology/metabolism ; Plant Leaves/growth & development/metabolism ; Plant Stomata/cytology/*growth & development ; Protein Structure, Tertiary
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  • 158
    Publication Date: 2008-08-23
    Description: The centromere is essential for the inheritance of genetic information on eukaryotic chromosomes. Epigenetic regulation of centromere identity has been implicated in genome stability, karyotype evolution, and speciation. However, little is known regarding the manner in which centromere dysfunction affects the chromosomal architectures. Here we show that in the fission yeast Schizosaccharomyces pombe, the conditional deletion of the centromere produces survivors that carry either a neocentromere-acquired chromosome at the subtelomeric region or an acentric chromosome rescued by intertelomere fusion with either of the remaining chromosomes. The ratio of neocentromere formation to telomere fusion is considerably decreased by the inactivation of genes involved in RNA interference-dependent heterochromatin formation. By affecting the modes of chromosomal reorganization, the genomic distribution of heterochromatin may influence the fate of karyotype evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ishii, Kojiro -- Ogiyama, Yuki -- Chikashige, Yuji -- Soejima, Saeko -- Masuda, Fumie -- Kakuma, Tatsuyuki -- Hiraoka, Yasushi -- Takahashi, Kohta -- New York, N.Y. -- Science. 2008 Aug 22;321(5892):1088-91. doi: 10.1126/science.1158699.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cell Biology, Institute of Life Science, Kurume University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18719285" target="_blank"〉PubMed〈/a〉
    Keywords: Centromere/*physiology ; Chromatin Immunoprecipitation ; Chromosome Segregation ; Chromosomes, Fungal/*physiology ; DNA Replication ; Gene Expression ; Genes, Fungal ; Heterochromatin/*metabolism ; Histones/metabolism ; Karyotyping ; Kinetochores/metabolism ; Methylation ; Mitosis ; Mutation ; Schizosaccharomyces/*genetics/physiology ; Schizosaccharomyces pombe Proteins/metabolism ; Telomere/*physiology
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  • 159
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-06-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berry, Richard M -- Armitage, Judith P -- New York, N.Y. -- Science. 2008 Jun 20;320(5883):1599-600. doi: 10.1126/science.1160444.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, Clarendon Lab, University of Oxford, Oxford OX1 3PU, UK. r.berry1@physics.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18566274" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus subtilis/genetics/*physiology ; Bacterial Proteins/genetics/*physiology ; Biofilms/*growth & development ; Flagella/*physiology ; Molecular Motor Proteins/*physiology ; Movement ; Mutation ; Operon
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  • 160
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2008 Aug 29;321(5893):1146-7. doi: 10.1126/science.321.5893.1146b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18755949" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Macular Degeneration/*genetics/therapy ; Mice ; Mutation ; RNA Interference ; RNA, Double-Stranded/administration & dosage/therapeutic use ; Toll-Like Receptor 3/*genetics
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  • 161
    Publication Date: 2008-02-09
    Description: The transcriptional response to auxin is critical for root and vascular development during Arabidopsis embryogenesis. Auxin induces the degradation of AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors, freeing their binding partners, the AUXIN RESPONSE FACTOR (ARF) proteins, which can activate transcription of auxin response genes. We show that TOPLESS (TPL) can physically interact with IAA12/BODENLOS (IAA12/BDL) through an ETHYLENE RESPONSE FACTOR (ERF)-associated amphiphilic repression (EAR) motif. TPL can repress transcription in vivo and is required for IAA12/BDL repressive activity. In addition, tpl-1 can suppress the patterning defects of the bdl-1 mutant. Direct interaction between TPL and ARF5/MONOPTEROS, which is regulated by IAA12/BDL, results in a loss-of-function arf5/mp phenotype. These observations show that TPL is a transcriptional co-repressor and further our understanding of how auxin regulates transcription during plant development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Szemenyei, Heidi -- Hannon, Mike -- Long, Jeff A -- GM072764/GM/NIGMS NIH HHS/ -- R01 GM072764/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Mar 7;319(5868):1384-6. doi: 10.1126/science.1151461. Epub 2008 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18258861" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Arabidopsis/embryology/*genetics/metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; DNA-Binding Proteins/metabolism ; *Gene Expression Regulation, Plant ; Indoleacetic Acids/*metabolism ; Models, Genetic ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/chemistry/metabolism ; Repressor Proteins/chemistry/genetics/*metabolism ; Seedlings/embryology/metabolism ; Seeds/embryology/metabolism ; Transcription Factors/metabolism ; *Transcription, Genetic ; Two-Hybrid System Techniques
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  • 162
    Publication Date: 2008-09-27
    Description: An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. The E-MAP uncovered a previously unidentified component of the RNA interference (RNAi) machinery (rsh1) and linked the RNAi pathway to several other biological processes. Comparison of the S. pombe E-MAP to an analogous genetic map from the budding yeast revealed that, whereas negative interactions were conserved between genes involved in similar biological processes, positive interactions and overall genetic profiles between pairs of genes coding for physically associated proteins were even more conserved. Hence, conservation occurs at the level of the functional module (protein complex), but the genetic cross talk between modules can differ substantially.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753251/" 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/PMC2753251/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roguev, Assen -- Bandyopadhyay, Sourav -- Zofall, Martin -- Zhang, Ke -- Fischer, Tamas -- Collins, Sean R -- Qu, Hongjing -- Shales, Michael -- Park, Han-Oh -- Hayles, Jacqueline -- Hoe, Kwang-Lae -- Kim, Dong-Uk -- Ideker, Trey -- Grewal, Shiv I -- Weissman, Jonathan S -- Krogan, Nevan J -- GM084279/GM/NIGMS NIH HHS/ -- R01 GM084279/GM/NIGMS NIH HHS/ -- R01 GM084279-01A1/GM/NIGMS NIH HHS/ -- R01 GM084279-02/GM/NIGMS NIH HHS/ -- R01 GM084279-02S1/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Oct 17;322(5900):405-10. doi: 10.1126/science.1162609. Epub 2008 Sep 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818364" target="_blank"〉PubMed〈/a〉
    Keywords: DNA Repair ; DNA Replication ; *Epistasis, Genetic ; Gene Expression Regulation, Fungal ; Gene Regulatory Networks ; *Genes, Fungal ; Histones/metabolism ; Mutation ; RNA Interference ; Saccharomyces cerevisiae/genetics/metabolism ; Schizosaccharomyces/*genetics/metabolism ; Schizosaccharomyces pombe Proteins/genetics/metabolism
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  • 163
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2008-05-10
    Description: The homeostatic framework has dominated our understanding of cellular physiology. We question whether homeostasis alone adequately explains microbial responses to environmental stimuli, and explore the capacity of intracellular networks for predictive behavior in a fashion similar to metazoan nervous systems. We show that in silico biochemical networks, evolving randomly under precisely defined complex habitats, capture the dynamical, multidimensional structure of diverse environments by forming internal representations that allow prediction of environmental change. We provide evidence for such anticipatory behavior by revealing striking correlations of Escherichia coli transcriptional responses to temperature and oxygen perturbations-precisely mirroring the covariation of these parameters upon transitions between the outside world and the mammalian gastrointestinal tract. We further show that these internal correlations reflect a true associative learning paradigm, because they show rapid decoupling upon exposure to novel environments.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931280/" 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/PMC2931280/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tagkopoulos, Ilias -- Liu, Yir-Chung -- Tavazoie, Saeed -- DP1 OD003787/OD/NIH HHS/ -- P50 GM071508/GM/NIGMS NIH HHS/ -- P50 GM071508-01/GM/NIGMS NIH HHS/ -- P50 GM071508-06/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jun 6;320(5881):1313-7. doi: 10.1126/science.1154456. Epub 2008 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18467556" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological ; Aerobiosis ; Anaerobiosis ; Computer Simulation ; Directed Molecular Evolution ; Ecosystem ; Escherichia coli/*genetics/growth & development/*physiology ; *Gene Regulatory Networks ; Homeostasis ; Kinetics ; *Metabolic Networks and Pathways ; Models, Biological ; Models, Statistical ; Mutation ; Oligonucleotide Array Sequence Analysis ; Oxygen/analysis ; Temperature ; *Transcription, Genetic
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  • 164
    Publication Date: 2008-08-16
    Description: During synaptic vesicle fusion, the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) protein syntaxin-1 exhibits two conformations that both bind to Munc18-1: a "closed" conformation outside the SNARE complex and an "open" conformation in the SNARE complex. Although SNARE complexes containing open syntaxin-1 and Munc18-1 are essential for exocytosis, the function of closed syntaxin-1 is unknown. We generated knockin/knockout mice that expressed only open syntaxin-1B. Syntaxin-1B(Open) mice were viable but succumbed to generalized seizures at 2 to 3 months of age. Binding of Munc18-1 to syntaxin-1 was impaired in syntaxin-1B(Open) synapses, and the size of the readily releasable vesicle pool was decreased; however, the rate of synaptic vesicle fusion was dramatically enhanced. Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235364/" 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/PMC3235364/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerber, Stefan H -- Rah, Jong-Cheol -- Min, Sang-Won -- Liu, Xinran -- de Wit, Heidi -- Dulubova, Irina -- Meyer, Alexander C -- Rizo, Josep -- Arancillo, Marife -- Hammer, Robert E -- Verhage, Matthijs -- Rosenmund, Christian -- Sudhof, Thomas C -- NS051262/NS/NINDS NIH HHS/ -- NS37200/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Sep 12;321(5895):1507-10. doi: 10.1126/science.1163174. Epub 2008 Aug 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18703708" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Epilepsy/etiology ; Excitatory Postsynaptic Potentials ; Membrane Fusion ; Mice ; Mice, Knockout ; Munc18 Proteins/metabolism ; Mutation ; Protein Conformation ; Protein Structure, Tertiary ; SNARE Proteins/metabolism ; Sucrose/metabolism ; Synapses/physiology ; Synaptic Vesicles/*physiology/ultrastructure ; Syntaxin 1/*chemistry/genetics/*metabolism
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  • 165
    Publication Date: 2008-11-08
    Description: The success of forward genetic (from phenotype to gene) approaches to uncover genes that drive the molecular mechanism of circadian clocks and control circadian behavior has been unprecedented. Links among genes, cells, neural circuits, and circadian behavior have been uncovered in the Drosophila and mammalian systems, demonstrating the feasibility of finding single genes that have major effects on behavior. Why was this approach so successful in the elucidation of circadian rhythms? This article explores the answers to this question and describes how the methods used successfully for identifying the molecular basis of circadian rhythms can be applied to other behaviors such as anxiety, addiction, and learning and memory.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744585/" 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/PMC3744585/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, Joseph S -- Shimomura, Kazuhiro -- Kumar, Vivek -- F32 DA024556/DA/NIDA NIH HHS/ -- P50 MH074924/MH/NIMH NIH HHS/ -- R01 MH078024/MH/NIMH NIH HHS/ -- U01 MH061915/MH/NIMH NIH HHS/ -- U01 MH61915/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 Nov 7;322(5903):909-12. doi: 10.1126/science.1158822.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208, USA. j-takahashi@northwestern.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18988844" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/genetics ; Behavior/*physiology ; Behavior, Addictive/genetics ; Behavior, Animal/*physiology ; Biological Clocks/*genetics ; Circadian Rhythm/*genetics ; *Genes ; *Genetic Techniques ; Humans ; Learning ; Mice ; Mutation ; Phenotype ; Point Mutation ; Sequence Analysis, DNA
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  • 166
    Publication Date: 2008-04-12
    Description: Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection. We identified endogenous siRNAs (endo-siRNAs), 21 nucleotides in length, that correspond to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. We also detected endo-siRNAs complementary to messenger RNAs (mRNAs); these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs requires the siRNA-generating ribonuclease Dicer-2 and the RNAi effector protein Argonaute2 (Ago2). We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953241/" 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/PMC2953241/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghildiyal, Megha -- Seitz, Herve -- Horwich, Michael D -- Li, Chengjian -- Du, Tingting -- Lee, Soohyun -- Xu, Jia -- Kittler, Ellen L W -- Zapp, Maria L -- Weng, Zhiping -- Zamore, Phillip D -- F30 AG030283-02/AG/NIA NIH HHS/ -- F30 AG030283-03/AG/NIA NIH HHS/ -- F30 AG030283-04/AG/NIA NIH HHS/ -- F30AG030283/AG/NIA NIH HHS/ -- GM080625/GM/NIGMS NIH HHS/ -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- HG003367/HG/NHGRI NIH HHS/ -- P30 AI042845/AI/NIAID NIH HHS/ -- P30 AI042845-119008/AI/NIAID NIH HHS/ -- R01 AI043208/AI/NIAID NIH HHS/ -- R01 AI043208-08/AI/NIAID NIH HHS/ -- R01 GM062862/GM/NIGMS NIH HHS/ -- R01 GM062862-08/GM/NIGMS NIH HHS/ -- R01 GM062862-09/GM/NIGMS NIH HHS/ -- R01 GM065236/GM/NIGMS NIH HHS/ -- R01 GM065236-07/GM/NIGMS NIH HHS/ -- R01 GM065236-08/GM/NIGMS NIH HHS/ -- R01 GM080625/GM/NIGMS NIH HHS/ -- R01 GM080625-02/GM/NIGMS NIH HHS/ -- R01 GM080625-03/GM/NIGMS NIH HHS/ -- R01 HG003367/HG/NHGRI NIH HHS/ -- R01 HG003367-03/HG/NHGRI NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- R37 GM062862-11/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2008 May 23;320(5879):1077-81. doi: 10.1126/science.1157396. Epub 2008 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18403677" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Base Sequence ; Cell Line ; *DNA Transposable Elements ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*genetics/metabolism ; Mutation ; RNA Helicases/genetics/metabolism ; *RNA Interference ; RNA, Double-Stranded/metabolism ; RNA, Messenger/*genetics ; RNA, Small Interfering/*genetics/*metabolism ; RNA-Induced Silencing Complex/genetics/metabolism ; Retroelements ; Ribonuclease III
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  • 167
    Publication Date: 2008-11-29
    Description: Stem cells within diverse tissues share the need for a chromatin configuration that promotes self-renewal, yet few chromatin proteins are known to regulate multiple types of stem cells. We describe a Drosophila gene, scrawny (scny), encoding a ubiquitin-specific protease, which is required in germline, epithelial, and intestinal stem cells. Like its yeast relative UBP10, Scrawny deubiquitylates histone H2B and functions in gene silencing. Consistent with previous studies of this conserved pathway of chromatin regulation, scny mutant cells have elevated levels of ubiquitinylated H2B and trimethylated H3K4. Our findings suggest that inhibiting H2B ubiquitylation through scny represents a common mechanism within stem cells that is used to repress the premature expression of key differentiation genes, including Notch target genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759887/" 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/PMC2759887/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buszczak, Michael -- Paterno, Shelley -- Spradling, Allan C -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Jan 9;323(5911):248-51. doi: 10.1126/science.1165678. Epub 2008 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution, Baltimore, MD 21218, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19039105" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/cytology/metabolism ; Animals ; Cell Differentiation ; Chromatin/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*cytology/genetics/metabolism ; Endopeptidases/*genetics/*metabolism ; Epithelial Cells/cytology/metabolism ; Female ; Gene Expression Regulation, Developmental ; Gene Silencing ; Germ Cells/cytology/metabolism ; Histones/*metabolism ; Intestines/cytology/metabolism ; Male ; Methylation ; Mutation ; Receptors, Notch/metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Stem Cells/cytology/*metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitin-Specific Proteases ; Ubiquitination
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  • 168
    Publication Date: 2008-12-20
    Description: The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity and is defined partly by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen-triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen-triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630859/" 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/PMC2630859/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clay, Nicole K -- Adio, Adewale M -- Denoux, Carine -- Jander, Georg -- Ausubel, Frederick M -- F32 AI066817-03/AI/NIAID NIH HHS/ -- R37 GM048707/GM/NIGMS NIH HHS/ -- R37-GM48707/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):95-101. doi: 10.1126/science.1164627. Epub 2008 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19095898" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/genetics/metabolism ; Aminoacyltransferases/genetics/metabolism ; Arabidopsis/genetics/*immunology/*metabolism/microbiology ; Arabidopsis Proteins/genetics/metabolism ; Ethylenes/metabolism ; Flagellin/*immunology ; Gene Expression Regulation, Plant ; Genes, Plant ; Glucans/biosynthesis ; Glucosinolates/*metabolism ; Glycoside Hydrolases/metabolism ; Hydrolysis ; *Immunity, Innate ; Indoles/metabolism/pharmacology ; Mutation ; N-Glycosyl Hydrolases/genetics/metabolism ; Peptide Fragments/immunology ; Salicylic Acid/metabolism/pharmacology ; Signal Transduction ; Transcription Factors/genetics/metabolism
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  • 169
    Publication Date: 2007-08-04
    Description: In flowering plants, signaling between the male pollen tube and the synergid cells of the female gametophyte is required for fertilization. In the Arabidopsis thaliana mutant feronia (fer), fertilization is impaired; the pollen tube fails to arrest and thus continues to grow inside the female gametophyte. FER encodes a synergid-expressed, plasma membrane-localized receptor-like kinase. We found that the FER protein accumulates asymmetrically in the synergid membrane at the filiform apparatus. Interspecific crosses using pollen from Arabidopsis lyrata and Cardamine flexuosa on A. thaliana stigmas resulted in a fer-like phenotype that correlates with sequence divergence in the extracellular domain of FER. Our findings show that the female control of pollen tube reception is based on a FER-dependent signaling pathway, which may play a role in reproductive isolation barriers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Escobar-Restrepo, Juan-Miguel -- Huck, Norbert -- Kessler, Sharon -- Gagliardini, Valeria -- Gheyselinck, Jacqueline -- Yang, Wei-Cai -- Grossniklaus, Ueli -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):656-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Plant Biology and Zurich-Basel Plant Science Center, University of Zurich, Zollikerstrasse 107, CH-8008 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673660" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/enzymology/genetics/*physiology ; Arabidopsis Proteins/chemistry/*genetics/*metabolism ; Brassicaceae/genetics/physiology ; Cell Membrane/enzymology ; Crosses, Genetic ; Evolution, Molecular ; Flowers/cytology/enzymology/*physiology ; Gene Expression ; Genes, Plant ; Germination ; Ligands ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Phosphotransferases/chemistry/*genetics/*metabolism ; Plant Epidermis/enzymology ; Pollen Tube/growth & development/*physiology ; Recombinant Fusion Proteins/metabolism ; Reproduction ; Seeds/growth & development ; Signal Transduction ; Species Specificity
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  • 170
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCormick, Sheila -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):606-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Gene Expression Center, USDA Agricultural Research Service-UC Berkeley, 800 Buchanan Street, Albany, CA 94710, USA. sheilamc@nature.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673644" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/enzymology/genetics/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Cell Membrane/enzymology ; Crosses, Genetic ; Evolution, Molecular ; Flowers/cytology/enzymology/*physiology ; Genes, Plant ; Ligands ; Models, Biological ; Mutation ; Phosphotransferases/*genetics/*metabolism ; Pollen Tube/growth & development/*physiology ; Reproduction ; Signal Transduction ; Species Specificity
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  • 171
    Publication Date: 2007-05-05
    Description: The initial electron transfer dynamics during photosynthesis have been studied in Rhodobacter sphaeroides reaction centers from wild type and 14 mutants in which the driving force and the kinetics of charge separation vary over a broad range. Surprisingly, the protein relaxation kinetics, as measured by tryptophan absorbance changes, are invariant in these mutants. By applying a reaction-diffusion model, we can fit the complex electron transfer kinetics of each mutant quantitatively, varying only the driving force. These results indicate that initial photosynthetic charge separation is limited by protein dynamics rather than by a static electron transfer barrier.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Haiyu -- Lin, Su -- Allen, James P -- Williams, Joann C -- Blankert, Sean -- Laser, Christa -- Woodbury, Neal W -- New York, N.Y. -- Science. 2007 May 4;316(5825):747-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biodesign Institute, Arizona State University, 1001 South McAllister Avenue, Tempe, AZ 85287-5201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478721" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry/genetics/*metabolism ; Bacteriochlorophylls/metabolism ; *Electron Transport ; Kinetics ; Light ; Models, Chemical ; Mutation ; *Photosynthesis ; Photosynthetic Reaction Center Complex Proteins/*chemistry/genetics/*metabolism ; Rhodobacter sphaeroides/genetics/*metabolism ; Spectrum Analysis ; Temperature ; Thermodynamics ; Tryptophan/chemistry
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  • 172
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2007 Jan 19;315(5810):314.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17234920" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Alzheimer Disease/*genetics/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Brain/metabolism ; Endosomes/metabolism ; Ethnic Groups/genetics ; Genetic Predisposition to Disease ; Humans ; LDL-Receptor Related Proteins/*genetics/metabolism ; Membrane Transport Proteins/*genetics/metabolism ; Mutation ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/metabolism ; Polymorphism, Single Nucleotide ; Protein Transport
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  • 173
    Publication Date: 2007-03-24
    Description: Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barrangou, Rodolphe -- Fremaux, Christophe -- Deveau, Helene -- Richards, Melissa -- Boyaval, Patrick -- Moineau, Sylvain -- Romero, Dennis A -- Horvath, Philippe -- New York, N.Y. -- Science. 2007 Mar 23;315(5819):1709-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Danisco USA Inc., 3329 Agriculture Drive, Madison, WI 53716, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17379808" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Bacterial/genetics ; DNA, Intergenic/*genetics ; Evolution, Molecular ; *Genes, Bacterial ; Genome, Viral ; Molecular Sequence Data ; Mutation ; Polymorphism, Single Nucleotide ; *Repetitive Sequences, Nucleic Acid ; Streptococcus Phages/genetics/*physiology ; Streptococcus thermophilus/*genetics/*virology ; Viral Plaque Assay ; Virus Replication
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  • 174
    Publication Date: 2007-03-24
    Description: Analysis of cellular components at multiple levels of biological information can provide valuable functional insights. We performed multiple high-throughput measurements to study the response of Escherichia coli cells to genetic and environmental perturbations. Analysis of metabolic enzyme gene disruptants revealed unexpectedly small changes in messenger RNA and proteins for most disruptants. Overall, metabolite levels were also stable, reflecting the rerouting of fluxes in the metabolic network. In contrast, E. coli actively regulated enzyme levels to maintain a stable metabolic state in response to changes in growth rate. E. coli thus seems to use complementary strategies that result in a metabolic network robust against perturbations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ishii, Nobuyoshi -- Nakahigashi, Kenji -- Baba, Tomoya -- Robert, Martin -- Soga, Tomoyoshi -- Kanai, Akio -- Hirasawa, Takashi -- Naba, Miki -- Hirai, Kenta -- Hoque, Aminul -- Ho, Pei Yee -- Kakazu, Yuji -- Sugawara, Kaori -- Igarashi, Saori -- Harada, Satoshi -- Masuda, Takeshi -- Sugiyama, Naoyuki -- Togashi, Takashi -- Hasegawa, Miki -- Takai, Yuki -- Yugi, Katsuyuki -- Arakawa, Kazuharu -- Iwata, Nayuta -- Toya, Yoshihiro -- Nakayama, Yoichi -- Nishioka, Takaaki -- Shimizu, Kazuyuki -- Mori, Hirotada -- Tomita, Masaru -- New York, N.Y. -- Science. 2007 Apr 27;316(5824):593-7. Epub 2007 Mar 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17379776" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatography, Liquid ; Computational Biology ; Electrophoresis, Capillary ; Electrophoresis, Gel, Two-Dimensional ; Enzyme Induction ; Enzyme Repression ; Enzymes/genetics/metabolism ; Escherichia coli/enzymology/*genetics/growth & development/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Gene Expression ; *Genes, Bacterial ; Mass Spectrometry ; *Metabolic Networks and Pathways/genetics ; Mutation ; Oligonucleotide Array Sequence Analysis ; Proteome ; RNA, Messenger/genetics/metabolism ; Systems Biology/*methods ; Transcription, Genetic
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  • 175
    Publication Date: 2007-09-01
    Description: MicroRNAs (miRNAs) repress hundreds of target messenger RNAs (mRNAs), but the physiological roles of specific miRNA-mRNA interactions remain largely elusive. We report that zebrafish microRNA-430 (miR-430) dampens and balances the expression of the transforming growth factor-beta (TGF-beta) Nodal agonist squint and the TGF-beta Nodal antagonist lefty. To disrupt the interaction of specific miRNA-mRNA pairs, we developed target protector morpholinos complementary to miRNA binding sites in target mRNAs. Protection of squint or lefty mRNAs from miR-430 resulted in enhanced or reduced Nodal signaling, respectively. Simultaneous protection of squint and lefty or absence of miR-430 caused an imbalance and reduction in Nodal signaling. These findings establish an approach to analyze the in vivo roles of specific miRNA-mRNA pairs and reveal a requirement for miRNAs in dampening and balancing agonist/antagonist pairs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Wen-Yee -- Giraldez, Antonio J -- Schier, Alexander F -- New York, N.Y. -- Science. 2007 Oct 12;318(5848):271-4. Epub 2007 Aug 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17761850" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Embryo, Nonmammalian/physiology ; Embryonic Development ; Gene Expression Regulation ; Left-Right Determination Factors ; MicroRNAs/*metabolism ; Mutation ; Nodal Protein ; Nodal Signaling Ligands ; RNA, Messenger/genetics/*metabolism ; Transforming Growth Factor beta/agonists/antagonists & ; inhibitors/*genetics/*metabolism ; Zebrafish/embryology/*genetics/metabolism ; Zebrafish Proteins/*genetics
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  • 176
    Publication Date: 2007-08-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, Robert F -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):884-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702918" target="_blank"〉PubMed〈/a〉
    Keywords: Aldosterone/metabolism ; Animals ; Computer Simulation ; Crystallography, X-Ray ; Desoxycorticosterone/metabolism ; *Evolution, Molecular ; *Fishes ; Hydrocortisone/metabolism ; Models, Molecular ; Mutation ; Protein Conformation ; Receptors, Glucocorticoid/chemistry/*genetics/metabolism ; Receptors, Mineralocorticoid/chemistry/*genetics/metabolism ; Receptors, Steroid/chemistry/*genetics/metabolism
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  • 177
    Publication Date: 2007-08-25
    Description: The organization of chromatin affects all aspects of nuclear DNA metabolism in eukaryotes. H3.3 is an evolutionarily conserved histone variant and a key substrate for replication-independent chromatin assembly. Elimination of chromatin remodeling factor CHD1 in Drosophila embryos abolishes incorporation of H3.3 into the male pronucleus, renders the paternal genome unable to participate in zygotic mitoses, and leads to the development of haploid embryos. Furthermore, CHD1, but not ISWI, interacts with HIRA in cytoplasmic extracts. Our findings establish CHD1 as a major factor in replacement histone metabolism in the nucleus and reveal a critical role for CHD1 in the earliest developmental instances of genome-scale, replication-independent nucleosome assembly. Furthermore, our results point to the general requirement of adenosine triphosphate (ATP)-utilizing motor proteins for histone deposition in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014568/" 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/PMC3014568/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Konev, Alexander Y -- Tribus, Martin -- Park, Sung Yeon -- Podhraski, Valerie -- Lim, Chin Yan -- Emelyanov, Alexander V -- Vershilova, Elena -- Pirrotta, Vincenzo -- Kadonaga, James T -- Lusser, Alexandra -- Fyodorov, Dmitry V -- GM58272/GM/NIGMS NIH HHS/ -- GM74233/GM/NIGMS NIH HHS/ -- R01 GM074233/GM/NIGMS NIH HHS/ -- Y 275/Austrian Science Fund FWF/Austria -- New York, N.Y. -- Science. 2007 Aug 24;317(5841):1087-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17717186" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Cell Cycle Proteins/metabolism ; Chromatin/*metabolism ; *Chromatin Assembly and Disassembly ; DNA-Binding Proteins/genetics/*metabolism ; Drosophila/embryology/genetics/metabolism/*physiology ; Drosophila Proteins/genetics/*metabolism ; Embryo, Nonmammalian/physiology ; Embryonic Development ; Female ; Haploidy ; Histone Chaperones ; Histones/*metabolism ; Male ; Mutation ; Nucleosomes/metabolism ; Protamines/metabolism ; Spermatozoa/physiology ; Transcription Factors/genetics/*metabolism ; Transgenes
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  • 178
    Publication Date: 2007-10-06
    Description: The RRM-domain proteins FCA and FPA have previously been characterized as flowering-time regulators in Arabidopsis. We show that they are required for RNA-mediated chromatin silencing of a range of loci in the genome. At some target loci, FCA and FPA promote asymmetric DNA methylation, whereas at others they function in parallel to DNA methylation. Female gametophytic development and early embryonic development are particularly susceptible to malfunctions in FCA and FPA. We propose that FCA and FPA regulate chromatin silencing of single and low-copy genes and interact in a locus-dependent manner with the canonical small interfering RNA-directed DNA methylation pathway to regulate common targets.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baurle, Isabel -- Smith, Lisa -- Baulcombe, David C -- Dean, Caroline -- New York, N.Y. -- Science. 2007 Oct 5;318(5847):109-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, UK. isabel.baurle@bbsrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17916737" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics/growth & development/metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Chromatin/*genetics ; DNA Methylation ; DNA Transposable Elements ; DNA, Plant/metabolism ; Flowers/growth & development ; Mutation ; Oxidoreductases/genetics ; *RNA Interference ; RNA, Plant/genetics ; RNA, Small Interfering/genetics ; RNA-Binding Proteins/chemistry/genetics/*metabolism ; Retroelements ; Transcription, Genetic
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  • 179
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flatt, Thomas -- Promislow, Daniel E L -- New York, N.Y. -- Science. 2007 Nov 23;318(5854):1255-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA. thomas_flatt@brown.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18033874" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*physiology ; Animals ; Biological Evolution ; Fertility ; Genes ; Humans ; Longevity/genetics ; Mutation ; Reproduction ; Selection, Genetic
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  • 180
    Publication Date: 2007-02-03
    Description: The 66-kilodalton isoform of the growth factor adapter Shc (p66Shc) translates oxidative damage into cell death by acting as reactive oxygen species (ROS) producer within mitochondria. However, the signaling link between cellular stress and mitochondrial proapoptotic activity of p66Shc was not known. We demonstrate that protein kinase C beta, activated by oxidative conditions in the cell, induces phosphorylation of p66Shc and triggers mitochondrial accumulation of the protein after it is recognized by the prolyl isomerase Pin1. Once imported, p66Shc causes alterations of mitochondrial Ca2+ responses and three-dimensional structure, thus inducing apoptosis. These data identify a signaling route that activates an apoptotic inducer shortening the life span and could be a potential target of pharmacological approaches to inhibit aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinton, Paolo -- Rimessi, Alessandro -- Marchi, Saverio -- Orsini, Francesca -- Migliaccio, Enrica -- Giorgio, Marco -- Contursi, Cristina -- Minucci, Saverio -- Mantovani, Fiamma -- Wieckowski, Mariusz R -- Del Sal, Giannino -- Pelicci, Pier Giuseppe -- Rizzuto, Rosario -- GGP05284/Telethon/Italy -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):659-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental and Diagnostic Medicine, Section of General Pathology and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrera, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272725" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adenosine Triphosphate/metabolism/pharmacology ; Animals ; *Apoptosis ; Calcium/metabolism ; Calcium Signaling ; *Cell Aging ; Cell Survival ; Cells, Cultured ; Cyclosporine/pharmacology ; Hydrogen Peroxide/metabolism/pharmacology ; Mice ; Mitochondria/*metabolism/ultrastructure ; Mutation ; Oxidative Stress ; Peptidylprolyl Isomerase/*metabolism ; Permeability ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors/genetics/*metabolism ; Protein Kinase C beta ; Reactive Oxygen Species/metabolism ; Recombinant Fusion Proteins/metabolism ; Shc Signaling Adaptor Proteins ; *Signal Transduction
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  • 181
    Publication Date: 2007-02-10
    Description: A central issue in the regulation of apoptosis by the Bcl-2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell-death mediators Bax and Bak, or whether they can act indirectly, by engaging their pro-survival Bcl-2-like relatives. Contrary to the direct-activation model, we show that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma. Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willis, Simon N -- Fletcher, Jamie I -- Kaufmann, Thomas -- van Delft, Mark F -- Chen, Lin -- Czabotar, Peter E -- Ierino, Helen -- Lee, Erinna F -- Fairlie, W Douglas -- Bouillet, Philippe -- Strasser, Andreas -- Kluck, Ruth M -- Adams, Jerry M -- Huang, David C S -- CA43540/CA/NCI NIH HHS/ -- CA80188/CA/NCI NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):856-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/chemistry/genetics/*metabolism ; BH3 Interacting Domain Death Agonist Protein/chemistry/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Humans ; Ligands ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Knockout ; Models, Biological ; Mutation ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins/metabolism ; Protein Structure, Tertiary ; Proteins/metabolism ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/chemistry/*metabolism ; bcl-Associated Death Protein/metabolism ; bcl-X Protein/metabolism
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  • 182
    Publication Date: 2007-09-29
    Description: The SAX-3/roundabout (Robo) receptor has SLT-1/Slit-dependent and -independent functions in guiding cell and axon migrations. We identified enhancer of ventral-axon guidance defects of unc-40 mutants (EVA-1) as a Caenorhabditis elegans transmembrane receptor for SLT-1. EVA-1 has two predicted galactose-binding ectodomains, acts cell-autonomously for SLT-1/Slit-dependent axon migration functions of SAX-3/Robo, binds to SLT-1 and SAX-3, colocalizes with SAX-3 on cells, and provides cell specificity to the activation of SAX-3 signaling by SLT-1. Double mutants of eva-1 or slt-1 with sax-3 mutations suggest that SAX-3 can (when slt-1 or eva-1 function is reduced) inhibit a parallel-acting guidance mechanism, which involves UNC-40/deleted in colorectal cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fujisawa, Kazuko -- Wrana, Jeffrey L -- Culotti, Joseph G -- NS41397/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Sep 28;317(5846):1934-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute of Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17901337" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Axons/*physiology ; Caenorhabditis elegans/cytology/genetics/growth & development/*physiology ; Caenorhabditis elegans Proteins/*chemistry/genetics/*metabolism ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Line ; Cell Movement ; Cloning, Molecular ; Humans ; Molecular Sequence Data ; Mutation ; Nerve Tissue Proteins/*metabolism ; Nervous System/growth & development/metabolism ; Neurons/physiology ; Protein Structure, Tertiary ; Receptors, Immunologic/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction
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  • 183
    Publication Date: 2007-11-03
    Description: The evolution of insect resistance threatens the effectiveness of Bacillus thuringiensis (Bt) toxins that are widely used in sprays and transgenic crops. Resistance to Bt toxins in some insects is linked with mutations that disrupt a toxin-binding cadherin protein. We show that susceptibility to the Bt toxin Cry1Ab was reduced by cadherin gene silencing with RNA interference in Manduca sexta, confirming cadherin's role in Bt toxicity. Native Cry1A toxins required cadherin to form oligomers, but modified Cry1A toxins lacking one alpha-helix did not. The modified toxins killed cadherin-silenced M. sexta and Bt-resistant Pectinophora gossypiella that had cadherin deletion mutations. Our findings suggest that cadherin promotes Bt toxicity by facilitating toxin oligomerization and demonstrate that the modified Bt toxins may be useful against pests resistant to standard Bt toxins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soberon, Mario -- Pardo-Lopez, Liliana -- Lopez, Idalia -- Gomez, Isabel -- Tabashnik, Bruce E -- Bravo, Alejandra -- 1R01 AI066014/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Dec 7;318(5856):1640-2. Epub 2007 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico. mario@ibt.unam.mx〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975031" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/chemistry/*genetics/metabolism/*toxicity ; Bacterial Toxins/chemistry/*genetics/metabolism/*toxicity ; Cadherins/genetics/metabolism ; Endotoxins/chemistry/*genetics/metabolism/*toxicity ; Genetic Engineering ; Hemolysin Proteins/chemistry/*genetics/metabolism/*toxicity ; *Insecticide Resistance ; Larva ; *Manduca/genetics/metabolism ; *Moths/genetics/metabolism ; Mutation ; *Pest Control, Biological ; RNA Interference
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  • 184
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2007 Sep 14;317(5844):1483.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17872415" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Diet ; Dietary Carbohydrates/administration & dosage/*metabolism ; *Gene Dosage ; Humans ; Mutation ; Pan troglodytes/genetics ; Saliva/enzymology ; Starch/*administration & dosage/*metabolism ; alpha-Amylases/*genetics/metabolism
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  • 185
    Publication Date: 2007-10-13
    Description: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Laura D -- Parsons, D Williams -- Jones, Sian -- Lin, Jimmy -- Sjoblom, Tobias -- Leary, Rebecca J -- Shen, Dong -- Boca, Simina M -- Barber, Thomas -- Ptak, Janine -- Silliman, Natalie -- Szabo, Steve -- Dezso, Zoltan -- Ustyanksky, Vadim -- Nikolskaya, Tatiana -- Nikolsky, Yuri -- Karchin, Rachel -- Wilson, Paul A -- Kaminker, Joshua S -- Zhang, Zemin -- Croshaw, Randal -- Willis, Joseph -- Dawson, Dawn -- Shipitsin, Michail -- Willson, James K V -- Sukumar, Saraswati -- Polyak, Kornelia -- Park, Ben Ho -- Pethiyagoda, Charit L -- Pant, P V Krishna -- Ballinger, Dennis G -- Sparks, Andrew B -- Hartigan, James -- Smith, Douglas R -- Suh, Erick -- Papadopoulos, Nickolas -- Buckhaults, Phillip -- Markowitz, Sanford D -- Parmigiani, Giovanni -- Kinzler, Kenneth W -- Velculescu, Victor E -- Vogelstein, Bert -- CA 43460/CA/NCI NIH HHS/ -- CA 57345/CA/NCI NIH HHS/ -- CA109274/CA/NCI NIH HHS/ -- CA112828/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- GM070219/GM/NIGMS NIH HHS/ -- GM07309/GM/NIGMS NIH HHS/ -- P30-CA43703/CA/NCI NIH HHS/ -- RR017698/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1108-13. Epub 2007 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics/metabolism ; Cell Line ; Chromosome Mapping ; Colorectal Neoplasms/*genetics/metabolism ; Computational Biology ; DNA, Neoplasm ; Databases, Genetic ; Genes, Neoplasm ; Genome, Human ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neoplasm Proteins/genetics/metabolism ; Sequence Analysis, DNA
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  • 186
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-07-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garber, Ken -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):190-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/*etiology/*genetics/pathology/physiopathology ; Brain/growth & development/pathology/physiopathology ; Carrier Proteins/genetics/metabolism ; Cell Adhesion Molecules, Neuronal ; Humans ; Learning ; Membrane Proteins/genetics/metabolism ; Memory ; Mutation ; Nerve Net/physiopathology ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/physiology ; Synapses/*physiology ; Synaptic Transmission
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  • 187
    Publication Date: 2007-01-27
    Description: Primary pneumonic plague is transmitted easily, progresses rapidly, and causes high mortality, but the mechanisms by which Yersinia pestis overwhelms the lungs are largely unknown. We show that the plasminogen activator Pla is essential for Y. pestis to cause primary pneumonic plague but is less important for dissemination during pneumonic plague than during bubonic plague. Experiments manipulating its temporal expression showed that Pla allows Y. pestis to replicate rapidly in the airways, causing a lethal fulminant pneumonia; if unexpressed, inflammation is aborted, and lung repair is activated. Inhibition of Pla expression prolonged the survival of animals with the disease, offering a therapeutic option to extend the period during which antibiotics are effective.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lathem, Wyndham W -- Price, Paul A -- Miller, Virginia L -- Goldman, William E -- AI53298/AI/NIAID NIH HHS/ -- DK52574/DK/NIDDK NIH HHS/ -- F32 AI069688-01/AI/NIAID NIH HHS/ -- NRSA T32 GM07067/GM/NIGMS NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 26;315(5811):509-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, 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/17255510" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Colony Count, Microbial ; Cytokines/genetics/metabolism ; Female ; Fibrinogen/metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Bacterial ; Lung/immunology/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mutation ; Plague/immunology/*microbiology/pathology ; Plasminogen/metabolism ; Plasminogen Activators/genetics/*metabolism ; Pneumonia, Bacterial/immunology/*microbiology/pathology ; Spleen/microbiology ; Tetracyclines/pharmacology ; Virulence Factors/genetics/metabolism ; Yersinia pestis/enzymology/genetics/growth & development/*pathogenicity
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  • 188
    Publication Date: 2007-08-25
    Description: Biotin-dependent multifunctional enzymes carry out metabolically important carboxyl group transfer reactions and are potential targets for the treatment of obesity and type 2 diabetes. These enzymes use a tethered biotin cofactor to carry an activated carboxyl group between distantly spaced active sites. The mechanism of this transfer has remained poorly understood. Here we report the complete structure of pyruvate carboxylase at 2.0 angstroms resolution, which shows its domain arrangement. The structure, when combined with mutagenic analysis, shows that intermediate transfer occurs between active sites on separate polypeptide chains. In addition, domain rearrangements associated with activator binding decrease the distance between active-site pairs, providing a mechanism for allosteric activation. This description provides insight into the function of biotin-dependent enzymes and presents a new paradigm for multifunctional enzyme catalysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉St Maurice, Martin -- Reinhardt, Laurie -- Surinya, Kathy H -- Attwood, Paul V -- Wallace, John C -- Cleland, W Wallace -- Rayment, Ivan -- AR35186/AR/NIAMS NIH HHS/ -- GM070455/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 24;317(5841):1076-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17717183" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/analogs & derivatives/metabolism ; Allosteric Regulation ; Binding Sites ; Biotin/*metabolism ; Catalytic Domain ; Coenzyme A/metabolism ; Crystallography, X-Ray ; Dimerization ; Enzyme Activators/metabolism ; Models, Molecular ; Mutation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Pyruvate Carboxylase/*chemistry/genetics/*metabolism ; Rhizobium etli/*enzymology
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  • 189
    Publication Date: 2007-07-07
    Description: Multiple DNA polymerases participate in replicating the leading and lagging strands of the eukaryotic nuclear genome. Although 50 years have passed since the first DNA polymerase was discovered, the identity of the major polymerase used for leading-strand replication is uncertain. We constructed a derivative of yeast DNA polymerase epsilon that retains high replication activity but has strongly reduced replication fidelity, particularly for thymine-deoxythymidine 5'-monophosphate (T-dTMP) but not adenine-deoxyadenosine 5'-monophosphate (A-dAMP) mismatches. Yeast strains with this DNA polymerase epsilon allele have elevated rates of T to A substitution mutations. The position and rate of these substitutions depend on the orientation of the mutational reporter and its location relative to origins of DNA replication and reveal a pattern indicating that DNA polymerase epsilon participates in leading-strand DNA replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233713/" 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/PMC2233713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pursell, Zachary F -- Isoz, Isabelle -- Lundstrom, Else-Britt -- Johansson, Erik -- Kunkel, Thomas A -- Z01 ES065070-17/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):127-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615360" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pair Mismatch ; DNA Polymerase II/genetics/*metabolism ; *DNA Replication ; DNA, Fungal/metabolism ; Fungal Proteins/genetics ; Mutation ; Point Mutation ; Replication Origin ; Saccharomyces cerevisiae/*enzymology/genetics
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  • 190
    Publication Date: 2007-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, Ann -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):364.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446367" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Antiporters/*genetics ; Diet ; Europe ; European Continental Ancestry Group/*genetics ; *Evolution, Molecular ; Humans ; Mutation ; Sequence Analysis, DNA ; Skin Pigmentation/*genetics ; Time ; Ultraviolet Rays ; Vitamin D/administration & dosage
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  • 191
    Publication Date: 2007-04-14
    Description: The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rhesus Macaque Genome Sequencing and Analysis Consortium -- Gibbs, Richard A -- Rogers, Jeffrey -- Katze, Michael G -- Bumgarner, Roger -- Weinstock, George M -- Mardis, Elaine R -- Remington, Karin A -- Strausberg, Robert L -- Venter, J Craig -- Wilson, Richard K -- Batzer, Mark A -- Bustamante, Carlos D -- Eichler, Evan E -- Hahn, Matthew W -- Hardison, Ross C -- Makova, Kateryna D -- Miller, Webb -- Milosavljevic, Aleksandar -- Palermo, Robert E -- Siepel, Adam -- Sikela, James M -- Attaway, Tony -- Bell, Stephanie -- Bernard, Kelly E -- Buhay, Christian J -- Chandrabose, Mimi N -- Dao, Marvin -- Davis, Clay -- Delehaunty, Kimberly D -- Ding, Yan -- Dinh, Huyen H -- Dugan-Rocha, Shannon -- Fulton, Lucinda A -- Gabisi, Ramatu Ayiesha -- Garner, Toni T -- Godfrey, Jennifer -- Hawes, Alicia C -- Hernandez, Judith -- Hines, Sandra -- Holder, Michael -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Khan, Ziad Mohid -- Kirkness, Ewen F -- Cree, Andrew -- Fowler, R Gerald -- Lee, Sandra -- Lewis, Lora R -- Li, Zhangwan -- Liu, Yih-Shin -- Moore, Stephanie M -- Muzny, Donna -- Nazareth, Lynne V -- Ngo, Dinh Ngoc -- Okwuonu, Geoffrey O -- Pai, Grace -- Parker, David -- Paul, Heidie A -- Pfannkoch, Cynthia -- Pohl, Craig S -- Rogers, Yu-Hui -- Ruiz, San Juana -- Sabo, Aniko -- Santibanez, Jireh -- Schneider, Brian W -- Smith, Scott M -- Sodergren, Erica -- Svatek, Amanda F -- Utterback, Teresa R -- Vattathil, Selina -- Warren, Wesley -- White, Courtney Sherell -- Chinwalla, Asif T -- Feng, Yucheng -- Halpern, Aaron L -- Hillier, Ladeana W -- Huang, Xiaoqiu -- Minx, Pat -- Nelson, Joanne O -- Pepin, Kymberlie H -- Qin, Xiang -- Sutton, Granger G -- Venter, Eli -- Walenz, Brian P -- Wallis, John W -- Worley, Kim C -- Yang, Shiaw-Pyng -- Jones, Steven M -- Marra, Marco A -- Rocchi, Mariano -- Schein, Jacqueline E -- Baertsch, Robert -- Clarke, Laura -- Csuros, Miklos -- Glasscock, Jarret -- Harris, R Alan -- Havlak, Paul -- Jackson, Andrew R -- Jiang, Huaiyang -- Liu, Yue -- Messina, David N -- Shen, Yufeng -- Song, Henry Xing-Zhi -- Wylie, Todd -- Zhang, Lan -- Birney, Ewan -- Han, Kyudong -- Konkel, Miriam K -- Lee, Jungnam -- Smit, Arian F A -- Ullmer, Brygg -- Wang, Hui -- Xing, Jinchuan -- Burhans, Richard -- Cheng, Ze -- Karro, John E -- Ma, Jian -- Raney, Brian -- She, Xinwei -- Cox, Michael J -- Demuth, Jeffery P -- Dumas, Laura J -- Han, Sang-Gook -- Hopkins, Janet -- Karimpour-Fard, Anis -- Kim, Young H -- Pollack, Jonathan R -- Vinar, Tomas -- Addo-Quaye, Charles -- Degenhardt, Jeremiah -- Denby, Alexandra -- Hubisz, Melissa J -- Indap, Amit -- Kosiol, Carolin -- Lahn, Bruce T -- Lawson, Heather A -- Marklein, Alison -- Nielsen, Rasmus -- Vallender, Eric J -- Clark, Andrew G -- Ferguson, Betsy -- Hernandez, Ryan D -- Hirani, Kashif -- Kehrer-Sawatzki, Hildegard -- Kolb, Jessica -- Patil, Shobha -- Pu, Ling-Ling -- Ren, Yanru -- Smith, David Glenn -- Wheeler, David A -- Schenck, Ian -- Ball, Edward V -- Chen, Rui -- Cooper, David N -- Giardine, Belinda -- Hsu, Fan -- Kent, W James -- Lesk, Arthur -- Nelson, David L -- O'brien, William E -- Prufer, Kay -- Stenson, Peter D -- Wallace, James C -- Ke, Hui -- Liu, Xiao-Ming -- Wang, Peng -- Xiang, Andy Peng -- Yang, Fan -- Barber, Galt P -- Haussler, David -- Karolchik, Donna -- Kern, Andy D -- Kuhn, Robert M -- Smith, Kayla E -- Zwieg, Ann S -- 062023/Wellcome Trust/United Kingdom -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003068/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):222-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. agibbs@bcm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431167" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research ; *Evolution, Molecular ; Female ; Gene Duplication ; Gene Rearrangement ; Genetic Diseases, Inborn ; Genetic Variation ; *Genome ; Humans ; Macaca mulatta/*genetics ; Male ; Multigene Family ; Mutation ; Pan troglodytes/genetics ; Sequence Analysis, DNA ; Species Specificity
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  • 192
    Publication Date: 2007-03-17
    Description: Escape from T cell-mediated immune responses affects the ongoing evolution of rapidly evolving viruses such as HIV. By applying statistical approaches that account for phylogenetic relationships among viral sequences, we show that viral lineage effects rather than immune escape often explain apparent human leukocyte antigen (HLA)-mediated immune-escape mutations defined by older analysis methods. Phylogenetically informed methods identified immune-susceptible locations with greatly improved accuracy, and the associations we identified with these methods were experimentally validated. This approach has practical implications for understanding the impact of host immunity on pathogen evolution and for defining relevant variants for inclusion in vaccine antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhattacharya, Tanmoy -- Daniels, Marcus -- Heckerman, David -- Foley, Brian -- Frahm, Nicole -- Kadie, Carl -- Carlson, Jonathan -- Yusim, Karina -- McMahon, Ben -- Gaschen, Brian -- Mallal, Simon -- Mullins, James I -- Nickle, David C -- Herbeck, Joshua -- Rousseau, Christine -- Learn, Gerald H -- Miura, Toshiyuki -- Brander, Christian -- Walker, Bruce -- Korber, Bette -- AI27757/AI/NIAID NIH HHS/ -- AI57005/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 16;315(5818):1583-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Los Alamos National Laboratory, Los Alamos, NM 87545, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17363674" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Antigen Presentation ; Epitopes ; Evolution, Molecular ; *Founder Effect ; Genes, MHC Class I ; Genes, Viral ; HIV Infections/immunology/*virology ; HIV-1/classification/*genetics/*immunology ; HLA Antigens/*genetics/immunology ; HLA-C Antigens/genetics ; Humans ; Immune Tolerance ; Likelihood Functions ; Mutation ; Phenotype ; Phylogeny ; *Polymorphism, Genetic ; T-Lymphocytes, Cytotoxic/immunology
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  • 193
    Publication Date: 2007-06-02
    Description: Leguminous plants (such as peas and soybeans) and rhizobial soil bacteria are symbiotic partners that communicate through molecular signaling pathways, resulting in the formation of nodules on legume roots and occasionally stems that house nitrogen-fixing bacteria. Nodule formation has been assumed to be exclusively initiated by the binding of bacterial, host-specific lipochito-oligosaccharidic Nod factors, encoded by the nodABC genes, to kinase-like receptors of the plant. Here we show by complete genome sequencing of two symbiotic, photosynthetic, Bradyrhizobium strains, BTAi1 and ORS278, that canonical nodABC genes and typical lipochito-oligosaccharidic Nod factors are not required for symbiosis in some legumes. Mutational analyses indicated that these unique rhizobia use an alternative pathway to initiate symbioses, where a purine derivative may play a key role in triggering nodule formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Giraud, Eric -- Moulin, Lionel -- Vallenet, David -- Barbe, Valerie -- Cytryn, Eddie -- Avarre, Jean-Christophe -- Jaubert, Marianne -- Simon, Damien -- Cartieaux, Fabienne -- Prin, Yves -- Bena, Gilles -- Hannibal, Laure -- Fardoux, Joel -- Kojadinovic, Mila -- Vuillet, Laurie -- Lajus, Aurelie -- Cruveiller, Stephane -- Rouy, Zoe -- Mangenot, Sophie -- Segurens, Beatrice -- Dossat, Carole -- Franck, William L -- Chang, Woo-Suk -- Saunders, Elizabeth -- Bruce, David -- Richardson, Paul -- Normand, Philippe -- Dreyfus, Bernard -- Pignol, David -- Stacey, Gary -- Emerich, David -- Vermeglio, Andre -- Medigue, Claudine -- Sadowsky, Michael -- New York, N.Y. -- Science. 2007 Jun 1;316(5829):1307-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Recherche pour le Developpement, Centre de Cooperation International en Recherche Agronomique pour le Developpement, Institut National de la Recherche Agronomique, Universite Montpellier 2, France. giraud@mpl.ird.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17540897" target="_blank"〉PubMed〈/a〉
    Keywords: Acyltransferases/genetics/metabolism ; Amidohydrolases/genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Bradyrhizobium/*genetics/growth & development/*physiology ; Cytokinins/metabolism ; Fabaceae/*microbiology ; Genes, Bacterial ; Genome, Bacterial ; Genomics ; Lipopolysaccharides/metabolism ; Molecular Sequence Data ; Mutation ; N-Acetylglucosaminyltransferases/genetics/metabolism ; Photosynthesis ; Plant Roots/microbiology ; Plant Stems/*microbiology ; Purines/biosynthesis ; Root Nodules, Plant/microbiology/*physiology ; Signal Transduction ; *Symbiosis
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  • 194
    Publication Date: 2007-08-19
    Description: The "segmentation clock" is thought to coordinate sequential segmentation of the body axis in vertebrate embryos. This clock comprises a multicellular genetic network of synchronized oscillators, coupled by intercellular Delta-Notch signaling. How this synchrony is established and how its loss determines the position of segmentation defects in Delta and Notch mutants are unknown. We analyzed the clock's synchrony dynamics by varying strength and timing of Notch coupling in zebra-fish embryos with techniques for quantitative perturbation of gene function. We developed a physical theory based on coupled phase oscillators explaining the observed onset and rescue of segmentation defects, the clock's robustness against developmental noise, and a critical point beyond which synchrony decays. We conclude that synchrony among these genetic oscillators can be established by simultaneous initiation and self-organization and that the segmentation defect position is determined by the difference between coupling strength and noise.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riedel-Kruse, Ingmar H -- Muller, Claudia -- Oates, Andrew C -- New York, N.Y. -- Science. 2007 Sep 28;317(5846):1911-5. Epub 2007 Aug 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstrasse 108, 01307 Dresden, Germany. ingmar@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702912" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*genetics/physiology ; *Body Patterning/genetics ; Dipeptides/pharmacology ; Embryo, Nonmammalian/metabolism ; *Embryonic Development ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Homeodomain Proteins/genetics/metabolism ; Intracellular Signaling Peptides and Proteins ; Mathematics ; Membrane Proteins/genetics/metabolism ; Mesoderm/physiology ; Mutation ; Nerve Tissue Proteins/genetics/metabolism ; Oligonucleotides, Antisense/pharmacology ; RNA Stability ; Receptor, Notch1/genetics/metabolism ; Signal Transduction ; Somites/physiology ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*metabolism
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  • 195
    Publication Date: 2007-07-14
    Description: Sister-chromatid cohesion, established during replication by the protein complex cohesin, is essential for both chromosome segregation and double-strand break (DSB) repair. Normally, cohesion formation is strictly limited to the S phase of the cell cycle, but DSBs can trigger cohesion also after DNA replication has been completed. The function of this damage-induced cohesion remains unknown. In this investigation, we show that damage-induced cohesion is essential for repair in postreplicative cells in yeast. Furthermore, it is established genome-wide after induction of a single DSB, and it is controlled by the DNA damage response and cohesin-regulating factors. We thus define a cohesion establishment pathway that is independent of DNA duplication and acts together with cohesion formed during replication in sister chromatid-based DSB repair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strom, Lena -- Karlsson, Charlotte -- Lindroos, Hanna Betts -- Wedahl, Sara -- Katou, Yuki -- Shirahige, Katsuhiko -- Sjogren, Camilla -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):242-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology, Karolinska Institute, 171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626884" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyltransferases/genetics/metabolism ; Cell Cycle Proteins/metabolism ; Cell Division ; Chromatids/*physiology ; Chromosomal Proteins, Non-Histone/metabolism ; *DNA Breaks, Double-Stranded ; *DNA Repair ; DNA Replication ; DNA, Fungal/biosynthesis/*metabolism ; G2 Phase ; Genome, Fungal ; Intracellular Signaling Peptides and Proteins ; Mutation ; Nuclear Proteins/genetics/metabolism ; Protein-Serine-Threonine Kinases ; Saccharomyces cerevisiae/genetics/metabolism/*physiology ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Signal Transduction
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  • 196
    Publication Date: 2007-02-03
    Description: Acetylation of histone H3 lysine 56 (H3-K56) occurs in S phase, and cells lacking H3-K56 acetylation are sensitive to DNA-damaging agents. However, the histone acetyltransferase (HAT) that catalyzes global H3-K56 acetylation has not been found. Here we show that regulation of Ty1 transposition gene product 109 (Rtt109) is an H3-K56 HAT. Cells lacking Rtt109 or expressing rtt109 mutants with alterations at a conserved aspartate residue lose H3-K56 acetylation and exhibit increased sensitivity toward genotoxic agents, as well as elevated levels of spontaneous chromosome breaks. Thus, Rtt109, which shares no sequence homology with any other known HATs, is a unique HAT that acetylates H3-K56.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Junhong -- Zhou, Hui -- Horazdovsky, Bruce -- Zhang, Kangling -- Xu, Rui-Ming -- Zhang, Zhiguo -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):653-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272723" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Camptothecin/pharmacology ; Catalytic Domain ; Chromosome Breakage ; DNA Damage ; *DNA Replication ; Histone Acetyltransferases/chemistry/genetics/*metabolism ; Histones/*metabolism ; Hydroxyurea/pharmacology ; Lysine/*metabolism ; Methyl Methanesulfonate/pharmacology ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutagens/pharmacology ; Mutation ; Recombinant Proteins/metabolism ; S Phase ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Sequence Homology, Amino Acid
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  • 197
    Publication Date: 2007-07-14
    Description: Changes in protein-protein interactions may allow polypeptides to perform unexpected regulatory functions. Mammalian ShcA docking proteins have amino-terminal phosphotyrosine (pTyr) binding (PTB) and carboxyl-terminal Src homology 2 (SH2) domains, which recognize specific pTyr sites on activated receptors, and a central region with two phosphorylated tyrosine-X-asparagine (pYXN) motifs (where X represents any amino acid) that each bind the growth factor receptor-bound protein 2 (Grb2) adaptor. Phylogenetic analysis indicates that ShcA may signal through both pYXN-dependent and -independent pathways. We show that, in mice, cardiomyocyte-expressed ShcA directs mid-gestational heart development by a PTB-dependent mechanism that does not require the pYXN motifs. In contrast, the pYXN motifs are required with PTB and SH2 domains in the same ShcA molecule for the formation of muscle spindles, skeletal muscle sensory organs that regulate motor behavior. Thus, combinatorial differences in ShcA docking interactions may yield multiple signaling mechanisms to support diversity in tissue morphogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575375/" 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/PMC2575375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hardy, W Rod -- Li, Lingying -- Wang, Zhi -- Sedy, Jiri -- Fawcett, James -- Frank, Eric -- Kucera, Jan -- Pawson, Tony -- R01 NS024373/NS/NINDS NIH HHS/ -- R01 NS024373-18/NS/NINDS NIH HHS/ -- R01 NS024373-19/NS/NINDS NIH HHS/ -- R01 NS024373-20/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):251-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626887" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism ; Amino Acid Motifs ; Animals ; Ataxia ; Excitatory Postsynaptic Potentials ; Genetic Complementation Test ; Heart/*embryology ; Mice ; Mice, Knockout ; *Morphogenesis ; Motor Activity ; Muscle Spindles/*embryology ; Muscle, Skeletal/*embryology/metabolism ; Mutation ; Myocytes, Cardiac/*metabolism ; Neurons, Afferent/physiology ; Phosphorylation ; Protein Structure, Tertiary ; Shc Signaling Adaptor Proteins ; Signal Transduction ; src Homology Domains
    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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  • 198
    Publication Date: 2007-04-21
    Description: Nearly half of the mammalian genome is composed of repeated sequences. In Drosophila, Piwi proteins exert control over transposons. However, mammalian Piwi proteins, MIWI and MILI, partner with Piwi-interacting RNAs (piRNAs) that are depleted of repeat sequences, which raises questions about a role for mammalian Piwi's in transposon control. A search for murine small RNAs that might program Piwi proteins for transposon suppression revealed developmentally regulated piRNA loci, some of which resemble transposon master control loci of Drosophila. We also find evidence of an adaptive amplification loop in which MILI catalyzes the formation of piRNA 5' ends. Mili mutants derepress LINE-1 (L1) and intracisternal A particle and lose DNA methylation of L1 elements, demonstrating an evolutionarily conserved role for PIWI proteins in transposon suppression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aravin, Alexei A -- Sachidanandam, Ravi -- Girard, Angelique -- Fejes-Toth, Katalin -- Hannon, Gregory J -- New York, N.Y. -- Science. 2007 May 4;316(5825):744-7. Epub 2007 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Howard Hughes Medical Institute (HHMI), 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446352" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Argonaute Proteins ; Cluster Analysis ; Computational Biology ; DNA Methylation ; Genes, Intracisternal A-Particle ; Long Interspersed Nucleotide Elements ; Male ; Meiosis ; Mice ; Mutation ; Proteins/*metabolism ; RNA, Antisense/genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; *Retroelements ; Reverse Transcriptase Polymerase Chain Reaction ; Short Interspersed Nucleotide Elements ; Spermatocytes/cytology/*metabolism ; Spermatogenesis ; *Suppression, Genetic
    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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  • 199
    Publication Date: 2007-06-30
    Description: Diapause is a protective response to unfavorable environments that results in a suspension of insect development and is most often associated with the onset of winter. The ls-tim mutation in the Drosophila melanogaster clock gene timeless has spread in Europe over the past 10,000 years, possibly because it enhances diapause. We show that the mutant allele attenuates the photosensitivity of the circadian clock and causes decreased dimerization of the mutant TIMELESS protein isoform to CRYPTOCHROME, the circadian photoreceptor. This interaction results in a more stable TIMELESS product. These findings reveal a molecular link between diapause and circadian photoreception.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandrelli, Federica -- Tauber, Eran -- Pegoraro, Mirko -- Mazzotta, Gabriella -- Cisotto, Paola -- Landskron, Johannes -- Stanewsky, Ralf -- Piccin, Alberto -- Rosato, Ezio -- Zordan, Mauro -- Costa, Rodolfo -- Kyriacou, Charalambos P -- New York, N.Y. -- Science. 2007 Jun 29;316(5833):1898-900.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Padova, 35131 Padova, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17600216" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *Circadian Rhythm/genetics ; Climate ; Cryptochromes ; Dimerization ; Drosophila Proteins/chemistry/*genetics/*metabolism ; Drosophila melanogaster/*genetics/metabolism/*physiology ; Europe ; Female ; Flavoproteins/*metabolism ; Light ; Motor Activity ; Mutation ; *Photoperiod ; Protein Isoforms/chemistry/genetics/metabolism ; Seasons ; *Selection, Genetic ; Temperature ; Transgenes ; Two-Hybrid System Techniques
    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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  • 200
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-06-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Downie, J Allan -- New York, N.Y. -- Science. 2007 Jun 1;316(5829):1296-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, UK. allan.downie@bbsrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17540893" target="_blank"〉PubMed〈/a〉
    Keywords: Acyltransferases/genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Bradyrhizobium/genetics/growth & development/*physiology ; Cytokinins/metabolism ; Fabaceae/*microbiology ; Genes, Bacterial ; Mutation ; N-Acetylglucosaminyltransferases/genetics/metabolism ; *Nitrogen Fixation ; Photosynthesis ; Plant Roots/microbiology ; Plant Stems/microbiology ; Purines/biosynthesis ; Root Nodules, Plant/microbiology/*physiology ; Signal Transduction ; *Symbiosis
    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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