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  • Lunar and Planetary Science and Exploration  (788)
  • Mutation  (187)
  • Analytical Chemistry and Spectroscopy
  • EARTH RESOURCES AND REMOTE SENSING
  • General Chemistry
  • Surface physics, nanoscale physics, low-dimensional systems
  • 2010-2014
  • 2000-2004  (975)
  • 1980-1984
  • 1925-1929
  • 2003  (975)
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  • 2010-2014
  • 2000-2004  (975)
  • 1980-1984
  • 1925-1929
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  • 101
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-11-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):774-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593147" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthropods/microbiology/physiology ; Eukaryota/physiology ; Fabaceae/microbiology/physiology ; Fungi/physiology ; Genes, Fungal ; Mutation ; Nitrogen Fixation ; Plant Physiological Phenomena ; Plants/microbiology ; Reproduction ; Rhizobium/physiology ; Scyphozoa/microbiology/physiology ; *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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  • 102
    Publication Date: 2003-10-11
    Description: Neuronal axons connect to multiple target cells through the formation of collateral branches, but the mechanisms that regulate this process are largely unknown. We show that BAM-2, a neurexin-related transmembrane protein, is required for development of VC motoneuron branches in the worm Caenorhabditis elegans. Expression analysis and ectopic expression experiments suggest that BAM-2 functions as a branch termination cue and reveal a mechanism for selective control of branches that sprout off a primary axon.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colavita, Antonio -- Tessier-Lavigne, Marc -- New York, N.Y. -- Science. 2003 Oct 10;302(5643):293-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14551437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Axons/*physiology/ultrastructure ; Caenorhabditis elegans/genetics/growth & development/*physiology/ultrastructure ; Caenorhabditis elegans Proteins/chemistry/genetics/*physiology ; Cues ; Female ; Gene Expression Profiling ; Genes, Helminth ; Growth Cones/physiology ; Ligands ; Membrane Proteins/chemistry/genetics/*physiology ; Molecular Sequence Data ; Motor Neurons/*physiology/ultrastructure ; Mutation ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Vulva/cytology/innervation
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  • 103
    Publication Date: 2003-06-28
    Description: The sorting of sodium channels to axons and the formation of clusters are of primary importance for neuronal electrogenesis. Here, we showed that the cytoplasmic loop connecting domains II and III of the Nav1 subunit contains a determinant conferring compartmentalization in the axonal initial segment of rat hippocampal neurons. Expression of a soluble Nav1.2II-III linker protein led to the disorganization of endogenous sodium channels. The motif was sufficient to redirect a somatodendritic potassium channel to the axonal initial segment, a process involving association with ankyrin G. Thus, this motif may play a fundamental role in controlling electrical excitability during development and plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garrido, Juan Jose -- Giraud, Pierre -- Carlier, Edmond -- Fernandes, Fanny -- Moussif, Anissa -- Fache, Marie-Pierre -- Debanne, Dominique -- Dargent, Benedicte -- New York, N.Y. -- Science. 2003 Jun 27;300(5628):2091-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Sante et de la Recherche Medicale Unite 464, Institut Jean Roche, Universite de la Mediterranee, Faculte de Medecine Secteur-Nord, Boulevard P. Dramard, 13916 Marseille Cedex 20, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12829783" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Ankyrins/metabolism ; Axons/*metabolism ; Cell Membrane/metabolism ; Delayed Rectifier Potassium Channels ; Hippocampus/cytology ; Humans ; Ion Channel Gating ; Molecular Sequence Data ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins/*chemistry/genetics/*metabolism ; Neurons/metabolism ; Patch-Clamp Techniques ; Potassium Channels/metabolism ; *Potassium Channels, Voltage-Gated ; Protein Structure, Tertiary ; Protein Transport ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Sodium Channels/*chemistry/genetics/*metabolism ; Transfection
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  • 104
    Publication Date: 2003-04-12
    Description: Kuru is an acquired prion disease largely restricted to the Fore linguistic group of the Papua New Guinea Highlands, which was transmitted during endocannibalistic feasts. Heterozygosity for a common polymorphism in the human prion protein gene (PRNP) confers relative resistance to prion diseases. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are, in marked contrast to younger unexposed Fore, predominantly PRNP 129 heterozygotes. Kuru imposed strong balancing selection on the Fore, essentially eliminating PRNP 129 homozygotes. Worldwide PRNP haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mead, Simon -- Stumpf, Michael P H -- Whitfield, Jerome -- Beck, Jonathan A -- Poulter, Mark -- Campbell, Tracy -- Uphill, James B -- Goldstein, David -- Alpers, Michael -- Fisher, Elizabeth M C -- Collinge, John -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):640-3. Epub 2003 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Prion Unit, and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690204" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cannibalism ; Child ; Codon ; Creutzfeldt-Jakob Syndrome/genetics ; Disease Outbreaks/*history ; Ethnic Groups/*genetics ; Female ; Gene Frequency ; Haplotypes ; Heterozygote ; History, 19th Century ; History, 20th Century ; History, Ancient ; Homozygote ; Humans ; Immunity, Innate ; Kuru/epidemiology/genetics/*history/transmission ; Linkage Disequilibrium ; Male ; Methionine/genetics ; Middle Aged ; Mutation ; Papua New Guinea/epidemiology ; *Polymorphism, Genetic ; PrPC Proteins/*genetics ; *Selection, Genetic ; Valine/genetics
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  • 105
    Publication Date: 2003-09-06
    Description: Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Melendez, Alicia -- Talloczy, Zsolt -- Seaman, Matthew -- Eskelinen, Eeva-Liisa -- Hall, David H -- Levine, Beth -- CA84254/CA/NCI NIH HHS/ -- RR 12596/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 5;301(5638):1387-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12958363" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Apoptosis Regulatory Proteins ; Autophagy/*genetics ; Caenorhabditis elegans/*genetics/*growth & development/metabolism/ultrastructure ; Caenorhabditis elegans Proteins/chemistry/*genetics/metabolism/physiology ; Genes, Fungal ; *Genes, Helminth ; Humans ; Longevity ; Membrane Proteins ; Morphogenesis ; Mutation ; Phagosomes/ultrastructure ; Phenotype ; Proteins/chemistry/genetics/physiology ; RNA Interference ; Receptor, Insulin/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/genetics/physiology ; Signal Transduction ; Vesicular Transport Proteins
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  • 106
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-11-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2003 Nov 14;302(5648):1134.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14615505" target="_blank"〉PubMed〈/a〉
    Keywords: *Diagnostic Techniques and Procedures ; Humans ; Indicators and Reagents ; Mutation ; *Oligonucleotide Array Sequence Analysis ; *Pharmacogenetics ; United States ; *United States Food and Drug Administration
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  • 107
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-01-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volkman, Sarah K -- Hartl, Daniel L -- New York, N.Y. -- Science. 2003 Jan 17;299(5605):353-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12532003" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Cat Diseases/parasitology/transmission ; Cats ; Female ; Food Parasitology ; Genes, Protozoan ; Genetic Variation ; Humans ; Life Cycle Stages ; Mice ; Mouth ; Mutation ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications, Parasitic/parasitology ; Recombination, Genetic ; Reproduction ; Toxoplasma/*genetics/pathogenicity/*physiology ; Toxoplasmosis/*parasitology/transmission ; Toxoplasmosis, Animal/*parasitology/transmission ; Toxoplasmosis, Congenital/epidemiology/parasitology ; Virulence
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  • 108
    Publication Date: 2003-12-20
    Description: The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gobert, Vanessa -- Gottar, Marie -- Matskevich, Alexey A -- Rutschmann, Sophie -- Royet, Julien -- Belvin, Marcia -- Hoffmann, Jules A -- Ferrandon, Dominique -- New York, N.Y. -- Science. 2003 Dec 19;302(5653):2126-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Unite Propre de Recherche 9022 du CNRS, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, F67084 Strasbourg Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14684822" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/*metabolism ; DNA Transposable Elements ; Drosophila/genetics/immunology/*metabolism/*microbiology ; Drosophila Proteins/genetics/*metabolism ; Gene Expression ; Genes, Insect ; Gram-Negative Bacteria/*physiology ; Gram-Positive Bacteria/*physiology ; Hemolymph/metabolism ; Hypocreales/physiology ; Insect Proteins/genetics/metabolism ; Mutation ; Phenotype ; Receptors, Cell Surface/genetics/*metabolism ; Serine Endopeptidases/genetics/metabolism ; Toll-Like Receptors
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  • 109
    Publication Date: 2003-03-22
    Description: The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2-mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plath, Kathrin -- Fang, Jia -- Mlynarczyk-Evans, Susanna K -- Cao, Ru -- Worringer, Kathleen A -- Wang, Hengbin -- de la Cruz, Cecile C -- Otte, Arie P -- Panning, Barbara -- Zhang, Yi -- New York, N.Y. -- Science. 2003 Apr 4;300(5616):131-5. Epub 2003 Mar 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12649488" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/metabolism/*physiology ; Cell Differentiation ; Cell Nucleus/metabolism ; Cells, Cultured ; *Dosage Compensation, Genetic ; Female ; Fluorescent Antibody Technique ; Genomic Imprinting ; HeLa Cells ; Histones/*metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Lysine/metabolism ; Male ; Methylation ; Mice ; Mutation ; Polycomb Repressive Complex 2 ; RNA, Long Noncoding ; RNA, Untranslated/genetics/metabolism ; Repressor Proteins/metabolism ; Stem Cells/metabolism/*physiology ; Transgenes ; Trophoblasts/*physiology ; X Chromosome/*metabolism
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  • 110
    Publication Date: 2003-05-24
    Description: Meiosis is a critical stage of gametogenesis in which alignment and synapsis of chromosomal pairs occur, allowing for the recombination of maternal and paternal genomes. Here we show that FK506 binding protein (Fkbp6) localizes to meiotic chromosome cores and regions of homologous chromosome synapsis. Targeted inactivation of Fkbp6 in mice results in aspermic males and the absence of normal pachytene spermatocytes. Moreover, we identified the deletion of Fkbp6 exon 8 as the causative mutation in spontaneously male sterile as/as mutant rats. Loss of Fkbp6 results in abnormal pairing and misalignments between homologous chromosomes, nonhomologous partner switches, and autosynapsis of X chromosome cores in meiotic spermatocytes. Fertility and meiosis are normal in Fkbp6 mutant females. Thus, Fkbp6 is a component of the synaptonemal complex essential for sex-specific fertility and for the fidelity of homologous chromosome pairing in meiosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882960/" 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/PMC2882960/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crackower, Michael A -- Kolas, Nadine K -- Noguchi, Junko -- Sarao, Renu -- Kikuchi, Kazuhiro -- Kaneko, Hiroyuki -- Kobayashi, Eiji -- Kawai, Yasuhiro -- Kozieradzki, Ivona -- Landers, Rushin -- Mo, Rong -- Hui, Chi-Chung -- Nieves, Edward -- Cohen, Paula E -- Osborne, Lucy R -- Wada, Teiji -- Kunieda, Tetsuo -- Moens, Peter B -- Penninger, Josef M -- 38103/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2003 May 23;300(5623):1291-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), c/o Dr. Bohrgasse 7, 1030, Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12764197" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apoptosis ; Chromosome Pairing/*physiology ; Cloning, Molecular ; Exons ; Female ; Fertility/*physiology ; Gene Targeting ; Humans ; Infertility, Male/genetics/*physiopathology ; Male ; *Meiosis ; Mice ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/genetics/metabolism ; Oogenesis ; Ovary/physiology ; Prophase ; Rats ; Sequence Deletion ; Spermatids/physiology ; Spermatocytes/physiology/ultrastructure ; Spermatogenesis ; Synaptonemal Complex/*physiology ; Tacrolimus Binding Proteins/chemistry/*genetics/*physiology ; Testis/physiology ; X Chromosome/physiology
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  • 111
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Lei -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):584-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA. lewang@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576413" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/analogs & derivatives/metabolism ; Awards and Prizes ; Codon ; Codon, Nonsense ; Codon, Terminator ; Escherichia coli/*genetics/metabolism ; *Genetic Code ; Kinetics ; Methanococcus/enzymology/genetics ; Methyltyrosines/*metabolism ; Mutation ; Naphthalenes/metabolism ; *Protein Biosynthesis ; RNA, Transfer/genetics/metabolism ; RNA, Transfer, Tyr/genetics/metabolism ; Suppression, Genetic ; Tetrahydrofolate Dehydrogenase/genetics/metabolism ; Tyrosine-tRNA Ligase/genetics/*metabolism
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  • 112
    Publication Date: 2003-12-04
    Description: During apoptosis, phosphatidylserine, which is normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and has been suggested to act as an "eat-me" signal to trigger phagocytosis. It is unclear how phagocytes recognize phosphatidylserine. Recently, a putative phosphatidylserine receptor (PSR) was identified and proposed to mediate recognition of phosphatidylserine and phagocytosis. We report that psr-1, the Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment. In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed phosphatidylserine. In C. elegans, PSR-1 acts in the same cell corpse engulfment pathway mediated by intracellular signaling molecules CED-2 (homologous to the human CrkII protein), CED-5 (DOCK180), CED-10 (Rac GTPase), and CED-12 (ELMO), possibly through direct interaction with CED-5 and CED-12. Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiaochen -- Wu, Yi-Chun -- Fadok, Valerie A -- Lee, Ming-Chia -- Gengyo-Ando, Keiko -- Cheng, Li-Chun -- Ledwich, Duncan -- Hsu, Pei-Ken -- Chen, Jia-Yun -- Chou, Bin-Kuan -- Henson, Peter -- Mitani, Shohei -- Xue, Ding -- New York, N.Y. -- Science. 2003 Nov 28;302(5650):1563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14645848" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Amino Acid Sequence ; Animals ; *Apoptosis ; Caenorhabditis elegans/cytology/embryology/metabolism/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Carrier Proteins/genetics/*metabolism ; *Cytoskeletal Proteins ; Embryo, Nonmammalian/cytology/metabolism ; Embryonic Development ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Membrane Proteins/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; *Phagocytosis ; Phosphatidylserines/metabolism ; Protein Binding ; Receptors, Cell Surface/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; Signal Transduction ; rac GTP-Binding Proteins/genetics/metabolism
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  • 113
    Publication Date: 2003-04-12
    Description: Signaling from the DAF-2/insulin receptor to the DAF-16/FOXO transcription factor controls longevity, metabolism, and development in disparate phyla. To identify genes that mediate the conserved biological outputs of daf-2/insulin-like signaling, we used comparative genomics to identify 17 orthologous genes from Caenorhabditis and Drosophila, each of which bears a DAF-16 binding site in the promoter region. One-third of these DAF-16 downstream candidate genes were regulated by daf-2/insulin-like signaling in C. elegans, and RNA interference inactivation of the candidates showed that many of these genes mediate distinct aspects of daf-16 function, including longevity, metabolism, and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Siu Sylvia -- Kennedy, Scott -- Tolonen, Andrew C -- Ruvkun, Gary -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):644-7. Epub 2003 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690206" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Caenorhabditis/genetics ; Caenorhabditis elegans/*genetics/metabolism/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Computational Biology ; Conserved Sequence ; Down-Regulation ; Drosophila/genetics ; Forkhead Transcription Factors ; Gene Expression Profiling ; Gene Expression Regulation ; *Genes, Helminth ; Genes, Insect ; Genomics ; Insulin/metabolism ; Longevity/genetics ; Mutation ; Promoter Regions, Genetic ; RNA Interference ; Receptor, Insulin/genetics/metabolism ; Signal Transduction ; Transcription Factors/*genetics/*physiology ; Up-Regulation
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  • 114
    Publication Date: 2003-10-25
    Description: Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex-restricted epitopes and failure to resolve HCV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grakoui, Arash -- Shoukry, Naglaa H -- Woollard, David J -- Han, Jin-Hwan -- Hanson, Holly L -- Ghrayeb, John -- Murthy, Krishna K -- Rice, Charles M -- Walker, Christopher M -- A14736/PHS HHS/ -- AI40034/AI/NIAID NIH HHS/ -- AI48231/AI/NIAID NIH HHS/ -- CA57973/CA/NCI NIH HHS/ -- CA85883/CA/NCI NIH HHS/ -- N01 HB27091/HB/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):659-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576438" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Antigen Presentation ; Antigens, Viral/chemistry/genetics/immunology ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Epitopes ; Evolution, Molecular ; Hepacivirus/genetics/*immunology/*physiology ; Hepatitis C/*immunology/virology ; *Immunologic Memory ; Liver/immunology ; Major Histocompatibility Complex ; Molecular Sequence Data ; Mutation ; Pan troglodytes ; T-Lymphocyte Subsets/immunology ; Time Factors ; Viral Core Proteins/chemistry/genetics/immunology ; Viral Nonstructural Proteins/chemistry/genetics/immunology ; Viremia ; Virus Replication
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  • 115
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-02-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Powrie, Fiona -- Maloy, Kevin J -- New York, N.Y. -- Science. 2003 Feb 14;299(5609):1030-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. fiona.powrie@path. ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12586934" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Autoimmune Diseases/immunology/prevention & control ; Cell Differentiation ; DNA-Binding Proteins/genetics/*metabolism ; Dendritic Cells/*immunology ; *Drosophila Proteins ; Forkhead Transcription Factors ; Graft Rejection/immunology ; Humans ; Immune Tolerance ; Immunity, Innate ; Interleukin-10/immunology ; Interleukin-6/immunology/secretion ; Lymphocyte Activation ; Membrane Glycoproteins/*physiology ; Mice ; Models, Immunological ; Mutation ; Receptors, Cell Surface/*physiology ; Receptors, Interleukin-2/analysis ; Signal Transduction ; T-Lymphocyte Subsets/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Thymus Gland/cytology/immunology ; Toll-Like Receptors ; Transduction, Genetic
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  • 116
    Publication Date: 2003-03-01
    Description: Ecdysone, the major steroid hormone of Drosophila melanogaster, is known for its role in development and reproduction. Flies that are heterozygous for mutations of the ecdysone receptor exhibit increases in life-span and resistance to various stresses, with no apparent deficit in fertility or activity. A mutant involved in the biosynthesis of ecdysone displays similar effects, which are suppressed by feeding ecdysone to the flies. These observations demonstrate the importance of the ecdysone hormonal pathway, a new player in regulating longevity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, Anne F -- Shih, Cindy -- Mack, Antha -- Benzer, Seymour -- AG16630/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1407-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 156-29, California Institute of Technology, 1201 California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610309" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Weight ; Crosses, Genetic ; Drosophila melanogaster/genetics/growth & development/*physiology ; Ecdysone/biosynthesis/*physiology ; Ecdysterone/administration & dosage/pharmacology ; Female ; Fertility ; Genes, Insect ; Ligands ; *Longevity ; Male ; Mutation ; Oxidative Stress ; Phototropism ; Receptors, Steroid/genetics/*physiology ; Starvation ; Temperature
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  • 117
    Publication Date: 2003-12-06
    Description: Myotonic dystrophy type 1 (DM1) is caused by a CUGn expansion (n approximately 50 to 5000) in the 3' untranslated region of the mRNA of the DM protein kinase gene. We show that mutant RNA binds and sequesters transcription factors (TFs), with up to 90% depletion of selected TFs from active chromatin. Diverse genes are consequently reduced in expression, including the ion transporter CIC-1, which has been implicated in myotonia. When TF specificity protein 1 (Sp1) was overexpressed in DM1-affected cells, low levels of messenger RNA for CIC-1 were restored to normal. Transcription factor leaching from chromatin by mutant RNA provides a potentially unifying pathomechanistic explanation for this disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ebralidze, A -- Wang, Y -- Petkova, V -- Ebralidse, K -- Junghans, R P -- New York, N.Y. -- Science. 2004 Jan 16;303(5656):383-7. Epub 2003 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biotherapeutics Development Lab, Harvard Institute of Human Genetics, Harvard Medical School and Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, 4 Blackfan Circle, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14657503" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cell Line ; Cell Nucleus/metabolism ; Chloride Channels/genetics ; Chromatin/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Humans ; Muscle Cells/*metabolism ; Mutation ; Myotonic Dystrophy/*genetics ; Myotonin-Protein Kinase ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases/*genetics ; RNA/genetics/*metabolism ; RNA Splicing ; RNA, Messenger/genetics/metabolism ; Receptors, IgG/genetics ; Receptors, Retinoic Acid/genetics/metabolism ; Ribonucleoproteins/metabolism ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; Sp1 Transcription Factor/genetics/metabolism ; Sp3 Transcription Factor ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/*metabolism ; *Transcription, Genetic
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  • 118
    Publication Date: 2003-11-25
    Description: The Arabidopsis FWA gene was initially identified from late-flowering epigenetic mutants that show ectopic FWA expression associated with heritable hypomethylation of repeats around transcription starting sites. Here, we show that wild-type FWA displays imprinted (maternal origin-specific) expression in endosperm. The FWA imprint depends on the maintenance DNA methyltransferase MET1, as is the case in mammals. Unlike mammals, however, the FWA imprint is not established by allele-specific de novo methylation. It is established by maternal gametophyte-specific gene activation, which depends on a DNA glycosylase gene, DEMETER. Because endosperm does not contribute to the next generation, the activated FWA gene need not be silenced again. Double fertilization enables plants to use such "one-way" control of imprinting and DNA methylation in endosperm.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kinoshita, Tetsu -- Miura, Asuka -- Choi, Yeonhee -- Kinoshita, Yuki -- Cao, Xiaofeng -- Jacobsen, Steven E -- Fischer, Robert L -- Kakutani, Tetsuji -- GM60398/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2004 Jan 23;303(5657):521-3. Epub 2003 Nov 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrated Genetics, National Institute of Genetics, Mishima 411-8540, Japan. tekinosh@lab.nig.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14631047" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Arabidopsis/*genetics/growth & development/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; DNA (Cytosine-5-)-Methyltransferase/metabolism ; *DNA Methylation ; DNA, Plant/genetics/metabolism ; DNA-Cytosine Methylases/genetics/metabolism ; *Gene Expression Regulation, Plant ; Gene Silencing ; *Genomic Imprinting ; Homeodomain Proteins/*genetics/metabolism ; Methyltransferases/genetics/metabolism ; Mutation ; N-Glycosyl Hydrolases/genetics/metabolism ; Pollen ; Recombinant Fusion Proteins/metabolism ; Repetitive Sequences, Nucleic Acid ; Reverse Transcriptase Polymerase Chain Reaction ; Seeds/*genetics/metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/*genetics/metabolism ; Transcription, Genetic ; Transcriptional Activation ; Transgenes
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  • 119
    Publication Date: 2003-05-17
    Description: The Caenorhabditis elegans transcription factor HSF-1, which regulates the heat-shock response, also influences aging. Reducing hsf-1 activity accelerates tissue aging and shortens life-span, and we show that hsf-1 overexpression extends lifespan. We find that HSF-1, like the transcription factor DAF-16, is required for daf-2-insulin/IGF-1 receptor mutations to extend life-span. Our findings suggest this is because HSF-1 and DAF-16 together activate expression of specific genes, including genes encoding small heat-shock proteins, which in turn promote longevity. The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting that these proteins couple the normal aging process to this type of age-related disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hsu, Ao-Lin -- Murphy, Coleen T -- Kenyon, Cynthia -- New York, N.Y. -- Science. 2003 May 16;300(5622):1142-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12750521" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*physiology ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/*physiology ; Forkhead Transcription Factors ; Gene Expression Regulation ; Heat-Shock Response/genetics/physiology ; Insulin/genetics/physiology ; Longevity/genetics/physiology ; Mutation ; Receptor, IGF Type 1/genetics/physiology ; Receptor, Insulin/genetics/physiology ; Transcription Factors/*physiology
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  • 120
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arantes-Oliveira, Nuno -- Berman, Jennifer R -- Kenyon, Cynthia -- R0I AG20932/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):611.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, 600 16th Street, Room S312D, University of California, San Francisco, San Francisco, CA 94143-2200, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576426" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Genes, Helminth ; Gonads/physiology ; *Longevity ; Movement ; Mutation ; RNA Interference ; Receptor, Insulin/genetics/*physiology
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  • 121
    Publication Date: 2003-06-14
    Description: The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) hypothesis suggests that pairs of proteins known as vesicle (v-) SNAREs and target membrane (t-) SNAREs interact specifically to control and mediate intracellular membrane fusion events. Here, cells expressing the interacting domains of v- and t-SNAREs on the cell surface were found to fuse spontaneously, demonstrating that SNAREs are sufficient to fuse biological membranes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Chuan -- Ahmed, Mahiuddin -- Melia, Thomas J -- Sollner, Thomas H -- Mayer, Thomas -- Rothman, James E -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1745-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 251, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805548" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Surface/chemistry/*metabolism ; COS Cells ; *Cell Fusion ; Cell Membrane/*metabolism ; Cercopithecus aethiops ; Endoplasmic Reticulum/metabolism ; Glycosylation ; Membrane Fusion/physiology ; Membrane Proteins/chemistry/genetics/*metabolism ; Mutation ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; R-SNARE Proteins ; Recombinant Fusion Proteins/metabolism ; Synaptosomal-Associated Protein 25 ; Syntaxin 1 ; Transfection
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  • 122
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-11-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klose, Robert -- Bird, Adrian -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):793-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Cell Biology, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593157" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors ; Brain-Derived Neurotrophic Factor/*genetics/physiology ; Cells, Cultured ; Chromatin/metabolism ; *Chromosomal Proteins, Non-Histone ; CpG Islands/*physiology ; *DNA Methylation ; DNA-Binding Proteins/genetics/*metabolism ; *Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Humans ; Methyl-CpG-Binding Protein 2 ; Mice ; Mutation ; Nervous System/embryology ; Neurons/metabolism ; Phosphorylation ; Potassium Chloride/pharmacology ; Promoter Regions, Genetic ; Rats ; *Repressor Proteins ; Rett Syndrome/genetics ; Transcription, Genetic ; Xenopus Proteins/genetics/metabolism ; Xenopus laevis
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  • 123
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-07-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taubes, Gary -- New York, N.Y. -- Science. 2003 Jul 4;301(5629):40-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12843374" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology/*etiology/metabolism ; Amyloid beta-Peptides/cerebrospinal fluid/*metabolism ; Animals ; Brain/*metabolism ; Diabetes Mellitus, Type 2/complications/metabolism ; Dietary Carbohydrates/administration & dosage ; Energy Intake ; Female ; Humans ; Insulin/blood/*metabolism ; Insulysin/genetics/*metabolism ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Mutation ; Risk Factors
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  • 124
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-11-01
    Description: We often think of neurodevelopmental disorders as beginning before birth, and many certainly do. A handful, however, strike many months after birth, following a period of apparently normal growth and development. Autism and Rett syndrome are two such disorders, and here I consider some of their similarities at the phenotypic and pathogenic levels. I propose that both disorders result from disruption of postnatal or experience-dependent synaptic plasticity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zoghbi, Huda Y -- HD 40301/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):826-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pediatrics, Neurology, and Molecular and Human Genetics, Division of Neuroscience, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. hzoghbi@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593168" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Animals ; Autistic Disorder/*etiology/genetics/metabolism/pathology ; Brain/*metabolism/pathology ; Carrier Proteins/genetics/metabolism ; Cell Adhesion Molecules, Neuronal ; Child, Preschool ; *Chromosomal Proteins, Non-Histone ; Chromosome Aberrations ; DNA-Binding Proteins/genetics/physiology ; Female ; Humans ; Infant ; *Intracellular Signaling Peptides and Proteins ; Magnetic Resonance Imaging ; Male ; Membrane Proteins/genetics/metabolism ; Methyl-CpG-Binding Protein 2 ; Mutation ; Nerve Tissue Proteins/genetics/metabolism ; Neuregulins/genetics/metabolism ; Neuronal Plasticity ; Neurons/pathology/*physiology ; Phenotype ; *Repressor Proteins ; Rett Syndrome/*etiology/genetics/metabolism/pathology ; Synapses/*physiology ; Ubiquitin-Protein Ligases/genetics/metabolism
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  • 125
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-06-07
    Description: The function of the ATR (ataxia-telangiectasia mutated- and Rad3-related)-ATRIP (ATR-interacting protein) protein kinase complex is crucial for the cellular response to replication stress and DNA damage. Here, we show that replication protein A (RPA), a protein complex that associates with single-stranded DNA (ssDNA), is required for the recruitment of ATR to sites of DNA damage and for ATR-mediated Chk1 activation in human cells. In vitro, RPA stimulates the binding of ATRIP to ssDNA. The binding of ATRIP to RPA-coated ssDNA enables the ATR-ATRIP complex to associate with DNA and stimulates phosphorylation of the Rad17 protein that is bound to DNA. Furthermore, Ddc2, the budding yeast homolog of ATRIP, is specifically recruited to double-strand DNA breaks in an RPA-dependent manner. A checkpoint-deficient mutant of RPA, rfa1-t11, is defective for recruiting Ddc2 to ssDNA both in vivo and in vitro. Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zou, Lee -- Elledge, Stephen J -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Jun 6;300(5625):1542-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna & Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12791985" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins/*metabolism ; Cell Nucleus/metabolism ; *DNA Damage ; DNA Repair ; DNA Replication ; DNA, Fungal/metabolism ; DNA, Single-Stranded/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Enzyme Activation ; *Exodeoxyribonucleases ; HeLa Cells ; Humans ; Mutation ; Phosphoproteins/*metabolism ; Phosphorylation ; Protein Binding ; Protein Kinases/metabolism ; *Protein-Serine-Threonine Kinases ; RNA, Small Interfering ; Radiation, Ionizing ; Recombination, Genetic ; Replication Protein A ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Signal Transduction ; Transcription Factors/genetics/metabolism ; Transfection ; Tumor Cells, Cultured ; Ultraviolet Rays
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  • 126
    Publication Date: 2003-10-25
    Description: RNA polymerase (RNAP) is the central enzyme of gene expression. Despite availability of crystal structures, details of its nucleotide addition cycle remain obscure. We describe bacterial RNAP inhibitors (the CBR703 series) whose properties illuminate this mechanism. These compounds inhibit known catalytic activities of RNAP (nucleotide addition, pyrophosphorolysis, and Gre-stimulated transcript cleavage) but not translocation of RNA or DNA when translocation is uncoupled from catalysis. CBR703-resistance substitutions occur on an outside surface of RNAP opposite its internal active site. We propose that CBR703 compounds inhibit nucleotide addition allosterically by hindering movements of active site structures that are linked to the CBR703 binding site through a bridge helix.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Artsimovitch, Irina -- Chu, Clement -- Lynch, A Simon -- Landick, Robert -- GM38660/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):650-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576436" target="_blank"〉PubMed〈/a〉
    Keywords: Amidines/chemistry/isolation & purification/metabolism/*pharmacology ; Binding Sites ; Catalysis ; DNA, Bacterial/metabolism ; DNA-Directed RNA Polymerases/*antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Drug Resistance, Bacterial ; Enzyme Inhibitors/chemistry/isolation & purification/metabolism/pharmacology ; Escherichia coli/*drug effects/genetics ; Exodeoxyribonucleases/metabolism ; Hydroxylamines/chemistry/isolation & purification/metabolism/*pharmacology ; Models, Molecular ; Mutation ; Nucleotides/*metabolism ; Phenylurea Compounds/chemistry/isolation & purification/metabolism/pharmacology ; Piperazines/chemistry/isolation & purification/pharmacology ; Promoter Regions, Genetic/drug effects ; Protein Conformation ; Protein Structure, Secondary ; Pyrazoles/chemistry/isolation & purification/pharmacology ; RNA, Bacterial/*biosynthesis ; Templates, Genetic ; Transcription, Genetic/*drug effects
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  • 127
    Publication Date: 2003-06-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Excoffier, Laurent -- Hamilton, Grant -- New York, N.Y. -- Science. 2003 Jun 20;300(5627):1877; author reply 1877.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computational and Molecular Population, Genetics LabZoological Institute, University of Bern, Batzerstrasse 63012, Bern, Switzerland. laurent.excoffier@zoo.unibe.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12817127" target="_blank"〉PubMed〈/a〉
    Keywords: Africa South of the Sahara ; Alleles ; Americas ; Asia ; Europe ; *Genetic Variation ; *Genetics, Population ; Humans ; *Microsatellite Repeats ; Mutation ; Pacific Islands
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  • 128
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-06-14
    Description: Most proteins have been formed by gene duplication, recombination, and divergence. Proteins of known structure can be matched to about 50% of genome sequences, and these data provide a quantitative description and can suggest hypotheses about the origins of these processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chothia, Cyrus -- Gough, Julian -- Vogel, Christine -- Teichmann, Sarah A -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1701-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Structural Studies Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805536" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Catalysis ; Computational Biology ; Enzymes/*chemistry/*genetics/metabolism ; *Evolution, Molecular ; Gene Duplication ; Genome ; Humans ; Metabolism ; Mutation ; Protein Structure, Tertiary ; Proteins/*chemistry/*genetics/metabolism ; Recombination, Genetic ; Substrate Specificity
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-11
    Description: Dynamics of proteins are crucial to their function. In his Perspective, Orrit stresses the advantages of studying these dynamics with single-molecule methods--which require no synchronization--rather than with conventional ensemble measurements. He highlights the report by Yang et al., who follow the fluorescence of a single enzyme molecule. Electron transfer from the fluorophore to a quencher induces fluctuations of the fluorescence lifetime along with the fluorophore-quencher distance. The wide range of characteristic times of those fluctuations reveals the complexity of the protein's potential energy landscape. As a new molecular ruler, electron transfer complements other single-molecule methods such as energy transfer (FRET) for distances shorter than a few nanometers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orrit, Michel -- New York, N.Y. -- Science. 2003 Oct 10;302(5643):239-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉NanoOptics and Spins, Leiden Institute of Physics, Leiden University, Post Office Box 9504, Netherlands. orrit@molphys.leidenuniv.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14551425" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Chemistry, Physical ; Electrons ; Escherichia coli/enzymology ; FMN Reductase/*chemistry/genetics/metabolism ; Flavin Mononucleotide/*chemistry/metabolism ; Flavin-Adenine Dinucleotide/*chemistry/metabolism ; Flavins/chemistry ; Fluorescence ; Hydrogen Bonding ; Lasers ; Likelihood Functions ; Mathematics ; Mutation ; Photons ; Physicochemical Phenomena ; *Protein Conformation ; Serine/chemistry ; Spectrometry, Fluorescence ; Temperature ; Thermodynamics ; Tyrosine
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  • 130
    Publication Date: 2003-11-08
    Description: Heparan sulfate (HS) is required for morphogen signaling during Drosophila pattern formation, but little is known about its physiological importance in mammalian development. To define the developmental role of HS in mammalian species, we conditionally disrupted the HS-polymerizing enzyme EXT1 in the embryonic mouse brain. The EXT1-null brain exhibited patterning defects that are composites of those caused by mutations of multiple HS-binding morphogens. Furthermore, the EXT1-null brain displayed severe guidance errors in major commissural tracts, revealing a pivotal role of HS in midline axon guidance. These findings demonstrate that HS is essential for mammalian brain development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Inatani, Masaru -- Irie, Fumitoshi -- Plump, Andrew S -- Tessier-Lavigne, Marc -- Yamaguchi, Yu -- P01 HD25938/HD/NICHD NIH HHS/ -- R01 NS33117/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 7;302(5647):1044-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Burnham Institute, 10901 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/14605369" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Body Patterning ; Brain/abnormalities/*embryology ; Cerebellum/embryology ; Cerebral Cortex/abnormalities/embryology ; Fibroblast Growth Factor 8 ; Fibroblast Growth Factors/metabolism ; Heparitin Sulfate/*physiology ; Homeodomain Proteins/metabolism ; Inferior Colliculi/embryology ; Intercellular Signaling Peptides and Proteins ; Mesencephalon/embryology ; Mice ; Mice, Knockout ; *Morphogenesis ; Mutation ; N-Acetylglucosaminyltransferases/genetics/metabolism ; Nerve Tissue Proteins/genetics/metabolism ; Optic Chiasm/cytology/embryology ; Proto-Oncogene Proteins/metabolism ; Retina/cytology ; Rhombencephalon/embryology ; Signal Transduction ; Wnt Proteins ; *Zebrafish Proteins
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  • 131
    Publication Date: 2003-06-07
    Description: In most eukaryotes cytokinesis is brought about by a contractile actin ring located at the division plane. Here, in fission yeast the actin ring was found to be required to generate late-mitotic microtubular structures located at the division plane, and these in turn maintained the medial position of the actin ring. When these microtubular structures were disrupted, the actin ring migrated away from the cell middle in a membrane traffic-dependent manner, resulting in asymmetrical cell divisions that led to genomic instability. We propose that these microtubular structures contribute to a checkpoint control that retains the equatorial position of the ring when progression through cytokinesis is delayed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pardo, Mercedes -- Nurse, Paul -- New York, N.Y. -- Science. 2003 Jun 6;300(5625):1569-74.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Cycle Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. mercedes.pardo@cancer.org.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12791993" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*physiology ; Anaphase ; Benzimidazoles/pharmacology ; Bicyclo Compounds, Heterocyclic/pharmacology ; *Carbamates ; Cell Cycle Proteins/physiology ; Cell Division/*physiology ; Cell Nucleus/physiology ; Cytoskeletal Proteins/physiology ; Interphase ; Microtubule-Organizing Center/physiology/ultrastructure ; Microtubules/*physiology/ultrastructure ; Mitosis ; Mutation ; Recombinant Fusion Proteins/metabolism ; Schizosaccharomyces/cytology/genetics/*physiology ; Schizosaccharomyces pombe Proteins/genetics/metabolism/physiology ; Temperature ; Thiazoles/pharmacology ; Thiazolidines ; Tubulin/metabolism
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  • 132
    Publication Date: 2003-10-04
    Description: Abnormally high spiking activity can damage neurons. Signaling systems to protect neurons from the consequences of abnormal discharge activity have been postulated. We generated conditional mutant mice that lack expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced excessive seizures in vivo. The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protective mechanisms could not be triggered in mutant mice. The endogenous cannabinoid system thus provides on-demand protection against acute excitotoxicity in central nervous system neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marsicano, Giovanni -- Goodenough, Sharon -- Monory, Krisztina -- Hermann, Heike -- Eder, Matthias -- Cannich, Astrid -- Azad, Shahnaz C -- Cascio, Maria Grazia -- Gutierrez, Silvia Ortega -- van der Stelt, Mario -- Lopez-Rodriguez, Maria Luz -- Casanova, Emilio -- Schutz, Gunther -- Zieglgansberger, Walter -- Di Marzo, Vincenzo -- Behl, Christian -- Lutz, Beat -- New York, N.Y. -- Science. 2003 Oct 3;302(5642):84-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Behaviour, Max-Planck-Institute of Psychiatry, Kraepelinstrabetae 2-10, 80804 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526074" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arachidonic Acids/*metabolism/pharmacology ; Brain/drug effects/*metabolism ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Cannabinoids/*metabolism ; Endocannabinoids ; Epilepsy/*metabolism/physiopathology ; Excitatory Amino Acid Agonists/pharmacology ; Excitatory Postsynaptic Potentials ; Furans/pharmacology ; Gene Expression Regulation/drug effects ; Genes, Immediate-Early ; Glutamic Acid/metabolism ; Glycerides/metabolism ; Hippocampus/drug effects/metabolism ; In Vitro Techniques ; Kainic Acid/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Neurons/drug effects/*metabolism/physiology ; Neuroprotective Agents/metabolism ; Piperidines/pharmacology ; Polyunsaturated Alkamides ; Prosencephalon/drug effects/metabolism ; Pyrazoles/pharmacology ; Receptors, Cannabinoid ; Receptors, Drug/antagonists & inhibitors/genetics/*metabolism ; Signal Transduction ; gamma-Aminobutyric Acid/metabolism
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-12-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2003 Dec 12;302(5652):1876-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14671257" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/metabolism ; Animals ; Biological Evolution ; Computational Biology ; *Evolution, Molecular ; *Genome ; *Genome, Human ; Humans ; Mice/genetics ; Mutation ; Pan troglodytes/*genetics ; *Selection, Genetic ; Sequence Homology, Nucleic Acid ; Signal Transduction/genetics ; Smell/genetics ; Species Specificity
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1505-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624245" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Animals ; Antiviral Agents/metabolism ; *Biological Evolution ; Capsid/metabolism ; Chemokines/chemistry ; HIV/genetics/*immunology/*pathogenicity/physiology ; HIV Antibodies/*immunology ; HIV Envelope Protein gp120/chemistry/immunology ; HIV Infections/immunology/*virology ; Humans ; *Immunity, Innate ; Molecular Mimicry ; Mutation ; Neutralization Tests ; Peptide Fragments/chemistry ; Protein Conformation ; Receptors, Chemokine/metabolism ; Receptors, HIV/metabolism ; Virus Replication
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  • 135
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-06-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2003 Jun 6;300(5625):1492-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12791957" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Calcium/metabolism ; Calcium-Binding Proteins/genetics/metabolism ; Calcium-Transporting ATPases/metabolism ; Cardiac Output, Low/etiology/physiopathology ; *Cardiomyopathy, Dilated/genetics/pathology/physiopathology ; *Cardiomyopathy, Hypertrophic, Familial/genetics/pathology/physiopathology ; Gene Expression Regulation ; Genes ; Heart/physiopathology ; Humans ; Mutation ; Myocardial Contraction ; Myocardium/metabolism ; Signal Transduction
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-12-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bastow, Ruth -- Dean, Caroline -- New York, N.Y. -- Science. 2003 Dec 5;302(5651):1695-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich, Norfolk NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14657484" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Arabidopsis/*genetics/*growth & development/metabolism ; Arabidopsis Proteins/*genetics/*metabolism ; Chromatin/metabolism ; Flowers/*growth & development ; Gene Expression Regulation, Plant ; Genes, Plant ; Histone Deacetylases/genetics/*metabolism ; Histones/*metabolism ; Introns ; MADS Domain Proteins/*genetics/*metabolism ; Mutation ; Regulatory Sequences, Nucleic Acid ; Sequence Homology, Amino Acid ; Transcription, Genetic
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-04-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frommer, Wolf B -- Schulze, Waltraud X -- Lalonde, Sylvie -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):261-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Physiology, Zentrum fur Molekularbiologie der Pflanzen, Universitat Tubingen, D-72076 Tubingen, Germany. frommer@zmbp.uni-tubingen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690178" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Arabidopsis/*enzymology/genetics/growth & development ; Biological Evolution ; Catalysis ; Cell Nucleus/metabolism ; Cytosol/enzymology ; Gene Expression Regulation ; Glucose/*metabolism ; Hexokinase/chemistry/genetics/*metabolism ; Humans ; Isoenzymes/metabolism ; Mutation ; Organelles/enzymology ; Phosphorylation ; Potassium Channels/metabolism ; Protein Conformation ; *Signal Transduction ; Yeasts/enzymology
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  • 138
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-06-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1692-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805532" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; Automatic Data Processing ; Biological Evolution ; Classification/*methods ; DNA/*analysis/genetics ; Databases, Factual ; *Ecosystem ; Electron Transport Complex IV/genetics ; Genes ; Internet ; Mammals/classification ; Mutation ; *Phylogeny ; Software
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  • 139
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McConnell, J R -- Barton, M K -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1328-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Biology, Carnegie Institution of Washington, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610287" target="_blank"〉PubMed〈/a〉
    Keywords: Antirrhinum/cytology/*genetics/*growth & development/metabolism ; Cell Differentiation ; Cell Division ; Cell Size ; DNA, Plant/metabolism ; *Gene Expression Regulation, Plant ; Genes, Plant ; Mutation ; Plant Leaves/anatomy & histology/cytology/*growth & development/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Transcription Factors/chemistry/genetics/*metabolism
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-05-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2003 May 16;300(5622):1062-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12750482" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Communicable Diseases, Emerging/diagnosis/epidemiology/virology ; *Disease Outbreaks ; Global Health ; Humans ; Mutation ; SARS Virus/classification/*genetics ; Severe Acute Respiratory Syndrome/diagnosis/*epidemiology/virology ; Swine ; Viral Proteins/chemistry/physiology
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):591-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576418" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ataxia Telangiectasia/genetics ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/physiology ; BRCA2 Protein/physiology ; Breast Neoplasms/*genetics ; Cell Cycle Proteins ; Cell Division ; DNA Damage ; DNA-Binding Proteins ; Estrogens/physiology ; Fanconi Anemia/genetics ; Female ; Genes, BRCA1/*physiology ; Genes, BRCA2/*physiology ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Male ; Mice ; Mutation ; Ovarian Neoplasms/*genetics ; Protein-Serine-Threonine Kinases/genetics/physiology ; Tumor Suppressor Proteins
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  • 142
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-09-27
    Description: There is a strong correlation between age and cancer, but the mechanism by which this phenomenon occurs is unclear. We chose Saccharomyces cerevisiae to examine one of the hallmarks of cancer--genomic instability--as a function of cellular age. As diploid yeast mother cells aged, an approximately 100-fold increase in loss of heterozygosity (LOH) occurred. Extending life-span altered neither the onset nor the frequency of age-induced LOH; the switch to hyper-LOH appears to be on its own clock. In young cells, LOH occurs by reciprocal recombination, whereas LOH in old cells was nonreciprocal, occurring predominantly in the old mother's progeny. Thus, nuclear genomes may be inherently unstable with age.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McMurray, Michael A -- Gottschling, Daniel E -- GM43893/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1908-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Basic Sciences, The Fred Hutchinson Cancer Research Center, and Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512629" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; *Cell Aging ; Cysteine Synthase ; DNA Replication ; DNA, Fungal/genetics/metabolism ; DNA, Ribosomal/genetics/metabolism ; DNA-Binding Proteins/genetics ; Diploidy ; Fungal Proteins/genetics ; Gene Deletion ; Genes, Fungal ; Histone Deacetylases/genetics ; *Loss of Heterozygosity ; *Multienzyme Complexes ; Mutation ; *Recombination, Genetic ; Saccharomyces cerevisiae/*genetics/*physiology ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics ; Sirtuin 2 ; Sirtuins/genetics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):592.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576419" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy/*genetics/prevention & control ; Female ; *Genes, BRCA1 ; *Genes, BRCA2 ; *Genetic Predisposition to Disease ; *Heterozygote ; Humans ; Mastectomy ; Mutation ; Ovarian Neoplasms/drug therapy/*genetics/prevention & control ; Ovariectomy ; Platinum/therapeutic use ; Risk Assessment ; Tamoxifen/therapeutic use
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  • 144
    Publication Date: 2003-06-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garsin, Danielle A -- Villanueva, Jacinto M -- Begun, Jakob -- Kim, Dennis H -- Sifri, Costi D -- Calderwood, Stephen B -- Ruvkun, Gary -- Ausubel, Frederick M -- GM48707/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Jun 20;300(5627):1921.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Massachusetts General Hospital, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12817143" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Caenorhabditis elegans/genetics/immunology/*microbiology/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Enterococcus faecalis/*pathogenicity/physiology ; Escherichia coli/*pathogenicity/physiology ; Forkhead Transcription Factors ; Longevity ; Mutation ; Phenotype ; Phosphatidylinositol 3-Kinases/genetics/physiology ; Receptor, Insulin/genetics/*physiology ; Staphylococcus aureus/*pathogenicity/physiology ; Transcription Factors/genetics/physiology
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  • 145
    Publication Date: 2003-04-12
    Description: The emergence of virulent Plasmodium falciparum in Africa within the past 6000 years as a result of a cascade of changes in human behavior and mosquito transmission has recently been hypothesized. Here, we provide genetic evidence for a sudden increase in the African malaria parasite population about 10,000 years ago, followed by migration to other regions on the basis of variation in 100 worldwide mitochondrial DNA sequences. However, both the world and some regional populations appear to be older (50,000 to 100,000 years old), suggesting an earlier wave of migration out of Africa, perhaps during the Pleistocene migration of human beings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joy, Deirdre A -- Feng, Xiaorong -- Mu, Jianbing -- Furuya, Tetsuya -- Chotivanich, Kesinee -- Krettli, Antoniana U -- Ho, May -- Wang, Alex -- White, Nicholas J -- Suh, Edward -- Beerli, Peter -- Su, Xin-zhuan -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):318-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA. djoy@niaid.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690197" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Agriculture ; Animals ; Anopheles/classification/genetics ; Asia ; DNA, Mitochondrial/*genetics ; DNA, Protozoan/genetics ; Emigration and Immigration ; Evolution, Molecular ; Genes, Protozoan ; *Genetic Variation ; Genome, Protozoan ; Haplotypes ; Humans ; Insect Vectors/classification/genetics ; Introns ; Likelihood Functions ; Malaria, Falciparum/parasitology/transmission ; Mutation ; Pan troglodytes/genetics ; Papua New Guinea ; Plasmodium/genetics ; *Plasmodium falciparum/genetics/physiology ; Polymorphism, Single Nucleotide ; Population Density ; RNA, Ribosomal/genetics ; Selection, Genetic ; Sequence Analysis, DNA ; South America ; Time
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  • 146
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cullimore, Julie -- Denarie, Jean -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):575-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire des Interactions Plantes-Microorganismes, CNRS-INRA, 31326 Castanet-Tolosan Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576408" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Physiological Phenomena ; Fabaceae/genetics/microbiology/*physiology ; Fungi/physiology ; *Genes, Plant ; Lipopolysaccharides/*metabolism ; Lotus/genetics/microbiology/physiology ; Medicago/genetics/microbiology/physiology ; Mutation ; Nitrogen Fixation ; Peas/genetics/microbiology/physiology ; Plant Roots/microbiology ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/*genetics/metabolism ; Rhizobium/growth & development/*physiology ; Signal Transduction ; Sinorhizobium meliloti/growth & development/*physiology ; *Symbiosis
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  • 147
    Publication Date: 2003-02-08
    Description: The vascular endothelium was once thought to function primarily in nutrient and oxygen delivery, but recent evidence suggests that it may play a broader role in tissue homeostasis. To explore the role of sinusoidal endothelial cells (LSECs) in the adult liver, we studied the effects of vascular endothelial growth factor (VEGF) receptor activation on mouse hepatocyte growth. Delivery of VEGF-A increased liver mass in mice but did not stimulate growth of hepatocytes in vitro, unless LSECs were also present in the culture. Hepatocyte growth factor (HGF) was identified as one of the LSEC-derived paracrine mediators promoting hepatocyte growth. Selective activation of VEGF receptor-1 (VEGFR-1) stimulated hepatocyte but not endothelial proliferation in vivo and reduced liver damage in mice exposed to a hepatotoxin. Thus, VEGFR-1 agonists may have therapeutic potential for preservation of organ function in certain liver disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LeCouter, Jennifer -- Moritz, Dirk R -- Li, Bing -- Phillips, Gail Lewis -- Liang, Xiao Huan -- Gerber, Hans-Peter -- Hillan, Kenneth J -- Ferrara, Napoleone -- New York, N.Y. -- Science. 2003 Feb 7;299(5608):890-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular Oncology, Protein Engineering, and Pathology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12574630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Carbon Tetrachloride/toxicity ; Cell Division ; Cells, Cultured ; Coculture Techniques ; Cricetinae ; DNA Replication ; Drug-Induced Liver Injury ; Endothelial Growth Factors/genetics/*metabolism/pharmacology ; Endothelium, Vascular/*cytology/physiology ; Gene Expression Regulation ; Growth Substances/genetics/metabolism ; Hepatocyte Growth Factor/genetics/metabolism/pharmacology ; Hepatocytes/cytology/pathology/*physiology ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism/pharmacology ; Liver/blood supply/*cytology/pathology/*physiology ; Liver Diseases/metabolism/pathology/prevention & control ; Liver Regeneration ; Lymphokines/genetics/*metabolism/pharmacology ; Mice ; Mice, Nude ; Mitosis ; Mutation ; Necrosis ; Neovascularization, Physiologic ; Paracrine Communication ; RNA, Messenger/genetics/metabolism ; Signal Transduction ; Up-Regulation ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1/*metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Vascular Endothelial Growth Factors
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  • 148
    Publication Date: 2003-12-06
    Description: In vitro studies have indicated that reactive oxygen species (ROS) and the oxidation of signaling molecules are important mediators of signal transduction. We have identified two pathways by which the altered redox chemistry of the clk-1 mutants of Caenorhabditis elegans acts in vivo on germline development. One pathway depends on the oxidation of an analog of vertebrate low density lipoprotein (LDL) and acts on the germline through the Ack-related tyrosine kinase (ARK-1) kinase and inositol trisphosphate (IP3) signaling. The other pathway is the oncogenic ras signaling pathway, whose action on germline as well as vulval development appears to be modulated by cytoplasmic ROS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shibata, Yukimasa -- Branicky, Robyn -- Landaverde, Irene Oviedo -- Hekimi, Siegfried -- New York, N.Y. -- Science. 2003 Dec 5;302(5651):1779-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, Quebec, Canada, H3A 1B1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14657502" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apolipoproteins B/genetics/metabolism ; Base Sequence ; Caenorhabditis elegans/genetics/*growth & development/*metabolism ; Caenorhabditis elegans Proteins/chemistry/genetics/metabolism ; Cholesterol/metabolism ; Cloning, Molecular ; Disorders of Sex Development ; Female ; Inositol Phosphates/metabolism ; Lipoproteins, LDL/*metabolism ; Molecular Sequence Data ; Mutation ; Oxidation-Reduction ; Phenotype ; Protein-Tyrosine Kinases/metabolism ; RNA Interference ; Reactive Oxygen Species/*metabolism ; Transcription Factors/genetics/metabolism ; Vulva/growth & development ; ras Proteins/genetics/metabolism
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  • 149
    Publication Date: 2003-05-24
    Description: The capsaicin receptor (TRPV1), a heat-activated ion channel of the pain pathway, is sensitized by phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis after phospholipase C activation. We identify a site within the C-terminal domain of TRPV1 that is required for PIP2-mediated inhibition of channel gating. Mutations that weaken PIP2-TRPV1 interaction reduce thresholds for chemical or thermal stimuli, whereas TRPV1 channels in which this region is replaced with a lipid-binding domain from PIP2-activated potassium channels remain inhibited by PIP2. The PIP2-interaction domain therefore serves as a critical determinant of thermal threshold and dynamic sensitivity range, tuning TRPV1, and thus the sensory neuron, to appropriately detect heat under normal or pathophysiological conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prescott, Elizabeth D -- Julius, David -- New York, N.Y. -- Science. 2003 May 23;300(5623):1284-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-2140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12764195" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arsenicals/pharmacology ; Binding Sites ; Capsaicin/metabolism/pharmacology ; Carrier Proteins ; Hot Temperature ; Humans ; Ion Channel Gating ; Membrane Proteins ; Molecular Sequence Data ; Mutation ; Oocytes ; Patch-Clamp Techniques ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phosphorylation ; Potassium Channels, Inwardly Rectifying/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Rats ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, trkA/metabolism ; Receptors, Drug/*chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Deletion ; Type C Phospholipases/metabolism ; Xenopus
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  • 150
    Publication Date: 2003-03-22
    Description: Mechanical unfolding trajectories for single molecules of the Tetrahymena thermophila ribozyme display eight intermediates corresponding to discrete kinetic barriers that oppose mechanical unfolding with lifetimes of seconds and rupture forces between 10 and 30 piconewtons. Barriers are magnesium dependent and correspond to known intra- and interdomain interactions. Several barrier structures are "brittle," breakage requiring high forces but small (1 to 3 nanometers) deformations. Barrier crossing is stochastic, leading to variable unfolding paths. The response of complex RNA structures to locally applied mechanical forces may be analogous to the responses of RNA during translation, messenger RNA export from the nucleus, and viral replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1503549/" 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/PMC1503549/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onoa, Bibiana -- Dumont, Sophie -- Liphardt, Jan -- Smith, Steven B -- Tinoco, Ignacio Jr -- Bustamante, Carlos -- GM-10840/GM/NIGMS NIH HHS/ -- GM-32543/GM/NIGMS NIH HHS/ -- R01 GM010840/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Mar 21;299(5614):1892-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Department of Molecular and Cell Biology and Howard Hughes Medical Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12649482" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Kinetics ; Magnesium ; Mutation ; Nucleic Acid Conformation ; Oligonucleotides, Antisense ; RNA, Catalytic/*chemistry/genetics ; Tetrahymena thermophila/*enzymology ; Thermodynamics
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  • 151
    Publication Date: 2003-09-23
    Description: Receptors for sex and adrenal steroid hormones are absent from fully sequenced invertebrate genomes and have not been recovered from other invertebrates. Here we report the isolation of an estrogen receptor ortholog from the mollusk Aplysia californica and the reconstruction, synthesis, and experimental characterization of functional domains of the ancestral protein from which all extant steroid receptors (SRs) evolved. Our findings indicate that SRs are extremely ancient and widespread, having diversified from a primordial gene before the origin of bilaterally symmetric animals, and that this ancient receptor had estrogen receptor-like functionality. This gene was lost in the lineage leading to arthropods and nematodes and became independent of hormone regulation in the Aplysia lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thornton, Joseph W -- Need, Eleanor -- Crews, David -- 41770/PHS HHS/ -- New York, N.Y. -- Science. 2003 Sep 19;301(5640):1714-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, OR 97403, USA. joet@uoregon.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14500980" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Aplysia/chemistry/genetics/*metabolism ; Biological Evolution ; CHO Cells ; Cloning, Molecular ; Cricetinae ; DNA/metabolism ; Estrogens/*metabolism/pharmacology ; *Evolution, Molecular ; Gene Duplication ; Humans ; Ligands ; Likelihood Functions ; Molecular Sequence Data ; Mutation ; *Phylogeny ; Polymerase Chain Reaction ; Protein Structure, Tertiary ; Receptors, Estrogen/chemistry/genetics/isolation & purification/*metabolism ; Receptors, Steroid/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Steroids/metabolism/pharmacology ; Transcription, Genetic ; Transfection
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  • 152
    Publication Date: 2003-02-08
    Description: We investigated the forces that connect the genetic program of development to morphogenesis in Drosophila. We focused on dorsal closure, a powerful model system for development and wound healing. We found that the bulk of progress toward closure is driven by contractility in supracellular "purse strings" and in the amnioserosa, whereas adhesion-mediated zipping coordinates the forces produced by the purse strings and is essential only for the end stages. We applied quantitative modeling to show that these forces, generated in distinct cells, are coordinated in space and synchronized in time. Modeling of wild-type and mutant phenotypes is predictive; although closure in myospheroid mutants ultimately fails when the cell sheets rip themselves apart, our analysis indicates that beta(PS) integrin has an earlier, important role in zipping.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hutson, M Shane -- Tokutake, Yoichiro -- Chang, Ming-Shien -- Bloor, James W -- Venakides, Stephanos -- Kiehart, Daniel P -- Edwards, Glenn S -- GM33830/GM/NIGMS NIH HHS/ -- GM61240/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 4;300(5616):145-9. Epub 2003 Feb 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics and Free Electron Laser Laboratory, Duke University, Durham, NC 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12574496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Cell Adhesion ; Drosophila/*embryology/genetics ; Drosophila Proteins/physiology ; Embryo, Nonmammalian/*physiology ; Embryonic Development ; Epithelial Cells/physiology ; Epithelium/physiology ; Genes, Insect ; Image Processing, Computer-Assisted ; Integrin alpha Chains ; Integrins/physiology ; Lasers ; Mathematics ; Microscopy, Confocal ; Microsurgery ; *Models, Biological ; *Morphogenesis ; Mutation ; Pseudopodia/physiology
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  • 153
    Publication Date: 2003-09-06
    Description: Although functions for the steroid hormone ecdysone during Drosophila metamorphosis have been well established, roles for the embryonic ecdysone pulse remain poorly understood. We show that the EcR-USP ecdysone receptor is first activated in the extraembryonic amnioserosa, implicating this tissue as a source of active ecdysteroids in the early embryo. Ecdysone signaling is required for germ band retraction and head involution, morphogenetic movements that shape the first instar larva. This mechanism for coordinating morphogenesis during Drosophila embryonic development parallels the role of ecdysone during metamorphosis. It also provides an intriguing parallel with the role of mammalian extraembryonic tissues as a critical source of steroid hormones during embryonic development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kozlova, Tatiana -- Thummel, Carl S -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1911-4. Epub 2003 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, 15 North 2030 East Room 5100, Salt Lake City, UT 84112-5331, USA. tkozlova@cas.usf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12958367" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA-Binding Proteins/genetics/*metabolism ; Drosophila/*embryology/metabolism ; Drosophila Proteins/genetics/metabolism ; Ecdysone/*metabolism ; Embryo, Nonmammalian/metabolism ; Embryonic Development ; Female ; Genes, Insect ; Genes, Reporter ; Integrin alpha Chains ; Integrins/genetics/metabolism ; Lac Operon ; Male ; Morphogenesis ; Mutation ; Receptors, Steroid/genetics/*metabolism ; Response Elements ; *Signal Transduction ; Transcription Factors/genetics/*metabolism
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  • 154
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hynes, Richard O -- New York, N.Y. -- Science. 2003 May 2;300(5620):755-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rohynes@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730590" target="_blank"〉PubMed〈/a〉
    Keywords: Biopolymers ; *Cell Adhesion ; Cell Membrane/*chemistry ; Cytoplasm/chemistry ; Dimerization ; Fibrinogen/metabolism ; Focal Adhesion Protein-Tyrosine Kinases ; Integrins/*chemistry/*metabolism ; Ligands ; Lipid Bilayers ; Models, Biological ; Mutation ; Platelet Glycoprotein GPIIb-IIIa Complex/*chemistry/genetics/*metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/metabolism ; Receptor Aggregation
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  • 155
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-10-11
    Description: A genetic screen was designed in Drosophila to interrogate its genome for mutations sufficient to cause noninvasive tumors of the eye disc to invade neighboring or distant tissues. We found that cooperation between oncogenic RasV12 expression and inactivation of any one of a number of genes affecting cell polarity leads to metastatic behavior, including basement membrane degradation, loss of E-cadherin expression, migration, invasion, and secondary tumor formation. Inactivation of these cell polarity genes cannot drive metastatic behavior alone or in combination with other tumor-initiating alterations. These findings suggest that the oncogenic background of tissues makes a distinct contribution toward metastatic development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pagliarini, Raymond A -- Xu, Tian -- CA69408/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Nov 14;302(5648):1227-31. Epub 2003 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14551319" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basement Membrane/metabolism ; Cadherins/metabolism ; Cell Division ; Cell Polarity/*genetics ; Drosophila Proteins/genetics/physiology ; Drosophila melanogaster/cytology/*genetics/physiology ; Epithelial Cells/physiology ; Eye ; Gene Silencing ; *Genes, Insect ; Genes, Tumor Suppressor ; Genes, ras ; Genetic Testing ; Green Fluorescent Proteins ; Luminescent Proteins ; Membrane Proteins/genetics/physiology ; *Models, Animal ; Mutation ; Neoplasm Metastasis/*genetics ; Neoplasms/genetics/pathology ; Transgenes
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  • 156
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-12-06
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1850956/" 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/PMC1850956/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tonkin, Leath A -- Bass, Brenda L -- GM44073/GM/NIGMS NIH HHS/ -- R01 GM044073/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Dec 5;302(5651):1725.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Howard Hughes Medical Institute, University of Utah, 20 North 1900 East, Salt Lake City, UT 84132-3201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14657490" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/genetics/*physiology ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/*physiology ; *Chemotaxis ; Crosses, Genetic ; Mutation ; RNA Editing ; *RNA Interference ; RNA, Double-Stranded/metabolism ; RNA, Helminth/metabolism ; RNA-Binding Proteins/genetics/physiology
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  • 157
    Publication Date: 2003-10-04
    Description: The most common inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1). In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells. Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology. Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clement, A M -- Nguyen, M D -- Roberts, E A -- Garcia, M L -- Boillee, S -- Rule, M -- McMahon, A P -- Doucette, W -- Siwek, D -- Ferrante, R J -- Brown, R H Jr -- Julien, J-P -- Goldstein, L S B -- Cleveland, D W -- AG 12992/AG/NIA NIH HHS/ -- AG 13846/AG/NIA NIH HHS/ -- HD 30249/HD/NICHD NIH HHS/ -- NS 27036/NS/NINDS NIH HHS/ -- NS 31248/NS/NINDS NIH HHS/ -- NS 37912/NS/NINDS NIH HHS/ -- R37 NS027036/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 3;302(5642):113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, University of California, 9500 Gilman Drive, La Jolla, CA 92093-0670, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526083" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*pathology ; Animals ; Axons/pathology ; Cell Survival ; Chimera ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Transgenic ; Motor Neurons/metabolism/pathology/*physiology ; Mutation ; Nerve Degeneration ; Neurofilament Proteins/metabolism ; Spinal Cord/metabolism/*pathology ; Superoxide Dismutase/*genetics/metabolism ; Survival Rate ; Ubiquitin/analysis
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  • 158
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-08-09
    Description: Recent insights into bacterial genome organization and function have improved our understanding of the nature of pathogenic bacteria and their ability to cause disease. It is becoming increasingly clear that the bacterial chromosome constantly undergoes structural changes due to gene acquisition and loss, recombination, and mutational events that have an impact on the pathogenic potential of the bacterium. Even though the bacterial genome includes additional genetic elements, the chromosome represents the most important entity in this context. Here, we will show that various processes of genomic instability have an influence on the many manifestations of infectious disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hacker, Jorg -- Hentschel, Ute -- Dobrindt, Ulrich -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):790-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Molekulare Infektionsbiologie, Universitat Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany. j.hacker@mail.uni-wuerzburg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907788" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Bacteria/*genetics/*pathogenicity ; Bacterial Infections/*microbiology ; Chromosomes, Bacterial/genetics/*physiology ; Drug Resistance, Bacterial/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genes, Bacterial ; Genome, Bacterial ; Humans ; Interspersed Repetitive Sequences ; Mutation ; Recombination, Genetic ; Symbiosis ; Virulence/genetics
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  • 159
    Publication Date: 2003-03-08
    Description: Photosynthetic organisms adapt to changes in light quality by redistributing light excitation energy between two photosystems through state transition. This reorganization of antenna systems leads to an enhanced photosynthetic yield. Using a genetic approach in Chlamydomonas reinhardtii to dissect the signal transduction pathway of state transition, we identified a chloroplast thylakoid-associated serine-threonine protein kinase, Stt7, that has homologs in land plants. Stt7 is required for the phosphorylation of the major light-harvesting protein (LHCII) and for state transition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Depege, Nathalie -- Bellafiore, Stephane -- Rochaix, Jean-David -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1572-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Department of Plant Biology, University of Geneva, 30 Quai Ernest Ansermet, 1211 Geneva 4, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624266" target="_blank"〉PubMed〈/a〉
    Keywords: Algal Proteins/chemistry/genetics/metabolism ; Alleles ; Amino Acid Sequence ; Animals ; Arabidopsis/enzymology/genetics ; Catalytic Domain ; Chlamydomonas reinhardtii/*enzymology/genetics/metabolism ; Chloroplasts/enzymology ; Cosmids ; DNA, Complementary ; Expressed Sequence Tags ; Fluorescence ; Genes ; Genetic Complementation Test ; Light ; Molecular Sequence Data ; Mutation ; Oxidation-Reduction ; Phosphorylation ; Photosynthesis ; Photosynthetic Reaction Center Complex Proteins/*metabolism ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Thylakoids/*enzymology ; Transcription, Genetic ; Transformation, Genetic
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  • 160
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-12-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sreenivasan, Aparna -- New York, N.Y. -- Science. 2003 Dec 19;302(5653):2050.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14684795" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Animals ; Calmodulin/metabolism ; Cell Nucleus/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Female ; Gonadal Dysgenesis, 46,XY/*etiology/genetics/metabolism ; Gonads/cytology/embryology/metabolism ; Humans ; Male ; Mice ; Mutation ; Nuclear Localization Signals ; Nuclear Pore/metabolism ; *Nuclear Proteins ; Protein Binding ; Sex-Determining Region Y Protein ; *Transcription Factors ; beta Karyopherins/metabolism
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  • 161
    Publication Date: 2003-09-27
    Description: The RNA interference (RNAi) pathway is initiated by processing long double-stranded RNA into small interfering RNA (siRNA). The siRNA-generating enzyme was purified from Drosophila S2cells and consists of two stoichiometric subunits: Dicer-2(DCR-2) and a previously unknown protein that we named R2D2. R2D2 is homologous to the Caenorhabditis elegans RNAi protein RDE-4. Association with R2D2 does not affect the enzymatic activity of DCR-2. Rather, the DCR-2/R2D2 complex, but not DCR-2 alone, binds to siRNA and enhances sequence-specific messenger RNA degradation mediated by the RNA-initiated silencing complex (RISC). These results indicate that R2D2 bridges the initiation and effector steps of the Drosophila RNAi pathway by facilitating siRNA passage from Dicer to RISC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Qinghua -- Rand, Tim A -- Kalidas, Savitha -- Du, Fenghe -- Kim, Hyun-Eui -- Smith, Dean P -- Wang, Xiaodong -- DC02539/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1921-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512631" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Argonaute Proteins ; Biotinylation ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/chemistry ; Cell Line ; Chemical Precipitation ; Drosophila Proteins/chemistry/genetics/*isolation & purification/*metabolism ; Drosophila melanogaster/*genetics/metabolism ; Electrophoretic Mobility Shift Assay ; Endoribonucleases/genetics/isolation & purification/*metabolism ; Kinetics ; Molecular Sequence Data ; Mutation ; Protein Structure, Tertiary ; RNA Helicases/genetics/*isolation & purification/*metabolism ; *RNA Interference ; RNA, Double-Stranded/metabolism ; RNA, Messenger/metabolism ; RNA, Small Interfering/*metabolism ; RNA-Binding Proteins/chemistry/genetics/isolation & purification/*metabolism ; RNA-Induced Silencing Complex/isolation & purification/metabolism ; Recombinant Proteins/metabolism ; Ribonuclease III
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  • 162
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-04-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dickson, Barry J -- New York, N.Y. -- Science. 2003 Apr 18;300(5618):440-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria. dickson@nt.imp.univie.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12702863" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Axons/*physiology ; Brain/cytology/growth & development/metabolism ; Carrier Proteins/genetics/*physiology ; Cell Size ; Drosophila/genetics/*growth & development/metabolism ; Drosophila Proteins/genetics/metabolism ; Insulin/*metabolism ; Insulin Receptor Substrate Proteins ; *Intracellular Signaling Peptides and Proteins ; Ligands ; Mutation ; Nerve Tissue Proteins/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Photoreceptor Cells, Invertebrate/cytology/*physiology ; *Protein-Serine-Threonine Kinases ; Protein-Tyrosine Kinases/genetics/*physiology ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; *Receptor Protein-Tyrosine Kinases ; Receptor, Insulin/genetics/*physiology ; Retina/cytology/growth & development ; *Signal Transduction ; Visual Pathways
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  • 163
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickens, Marvin -- Goldstrohm, Aaron -- New York, N.Y. -- Science. 2003 May 2;300(5620):753-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA. wickens@biochem.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730589" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Cytoplasm/metabolism ; Cytoplasmic Granules/metabolism/ultrastructure ; Cytoplasmic Structures/*metabolism/ultrastructure ; DEAD-box RNA Helicases ; Endoribonucleases/metabolism ; Exoribonucleases/genetics/metabolism ; Models, Biological ; Mutation ; Neurons/metabolism ; Oogenesis ; Poly A/metabolism ; Protein Biosynthesis ; RNA Cap-Binding Proteins ; RNA Caps/*metabolism ; RNA Helicases/metabolism ; RNA, Fungal/metabolism ; RNA, Messenger/genetics/*metabolism ; RNA-Binding Proteins/metabolism ; Ribonucleases/metabolism ; Saccharomyces cerevisiae/genetics/*metabolism/ultrastructure ; Saccharomyces cerevisiae Proteins/genetics/metabolism
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  • 164
    Publication Date: 2003-03-01
    Description: Restriction of the number of calories consumed extends longevity in many organisms. In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation without irreversible side effects. In organisms ranging from yeast to mice, mutations in glucose or IGF-I-like signaling pathways extend life-span but also cause glycogen or fat accumulation and dwarfism. This information suggests a new category of drugs that could prevent or postpone diseases of aging with few adverse effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Longo, Valter D -- Finch, Caleb E -- AG 01028/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1342-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Andrus Gerontology Center, Division of Biogerontology, and Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA. vlongo@usc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610293" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Biological Evolution ; Caenorhabditis elegans/genetics/physiology ; Caloric Restriction ; Drosophila/genetics/physiology ; Dwarfism/physiopathology ; Gene Expression Regulation ; Glucose/*metabolism ; Growth Hormone/metabolism ; Human Growth Hormone/metabolism ; Humans ; Insulin-Like Growth Factor I/*metabolism ; *Longevity/genetics ; Mice ; Models, Animal ; Mutation ; Signal Transduction ; Yeasts/genetics/physiology
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  • 165
    Publication Date: 2003-12-06
    Description: Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of alpha-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were sensitive to a mutant huntingtin fragment, 86 that were sensitive to alpha-synuclein, and only one mutant that was sensitive to both. Genes that enhanced toxicity of the mutant huntingtin fragment clustered in the functionally related cellular processes of response to stress, protein folding, and ubiquitin-dependent protein catabolism, whereas genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport. Genes with human orthologs were overrepresented in our screens, suggesting that we may have discovered conserved and nonoverlapping sets of cell-autonomous genes and pathways that are relevant to Huntington's disease and Parkinson's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willingham, Stephen -- Outeiro, Tiago Fleming -- DeVit, Michael J -- Lindquist, Susan L -- Muchowski, Paul J -- New York, N.Y. -- Science. 2003 Dec 5;302(5651):1769-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14657499" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Transport ; Gene Deletion ; Genes, Fungal ; Humans ; Lipid Metabolism ; Mutation ; Nerve Tissue Proteins/*genetics/*physiology ; Nitrosation ; Nuclear Proteins/*genetics/*physiology ; Osmotic Pressure ; Oxidative Stress ; Protein Folding ; Proteins/metabolism ; Saccharomyces cerevisiae/*genetics/metabolism ; Synucleins ; Transformation, Genetic ; Ubiquitin/metabolism ; alpha-Synuclein
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  • 166
    Publication Date: 2003-05-06
    Description: Transmembrane helices of integrin alpha and beta subunits have been implicated in the regulation of integrin activity. Two mutations, glycine-708 to asparagine-708 (G708N)and methionine-701 to asparagine-701, in the transmembrane helix of the beta3 subunit enabled integrin alphaIIbbeta3 to constitutively bind soluble fibrinogen. Further characterization of the G708N mutant revealed that it induced alphaIIbbeta3 clustering and constitutive phosphorylation of focal adhesion kinase. This mutation also enhanced the tendency of the transmembrane helix to form homotrimers. These results suggest that homomeric associations involving transmembrane domains provide a driving force for integrin activation. They also suggest a structural basis for the coincidence of integrin activation and clustering.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Renhao -- Mitra, Neal -- Gratkowski, Holly -- Vilaire, Gaston -- Litvinov, Rustem -- Nagasami, Chandrasekaran -- Weisel, John W -- Lear, James D -- DeGrado, William F -- Bennett, Joel S -- HL40387/HL/NHLBI NIH HHS/ -- HL54500/HL/NHLBI NIH HHS/ -- K01 CA096706/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 May 2;300(5620):795-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12730600" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Antibodies, Monoclonal/metabolism ; Biopolymers ; CHO Cells ; Cell Adhesion ; Cell Membrane/*chemistry ; Cricetinae ; Cricetulus ; Dimerization ; Fibrinogen/metabolism ; Fluorescein-5-isothiocyanate ; Focal Adhesion Protein-Tyrosine Kinases ; Ligands ; Microscopy, Fluorescence ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Platelet Glycoprotein GPIIb-IIIa Complex/*chemistry/genetics/*metabolism ; Protein Conformation ; *Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/metabolism ; Receptor Aggregation
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  • 167
    Publication Date: 2003-01-04
    Description: Selection can favor reproductive altruism if an altruism allele aids copies of itself by helping relatives. The alternative "greenbeard" mechanism, in which an allele directly recognizes and aids copies of itself in others, is generally thought to be too complex for a single gene to carry out. The csA gene in Dictyostelium discoideum acts as a single-gene greenbeard. When wild-type cells are mixed with csA-knockout cells, the wild type is more altruistic, but is also able preferentially to direct the benefits to other wild-type cells. Both properties derive directly from homophilic cell adhesion of the protein encoded by csA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Queller, David C -- Ponte, Eleonora -- Bozzaro, Salvatore -- Strassmann, Joan E -- New York, N.Y. -- Science. 2003 Jan 3;299(5603):105-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, MS-170, Rice University, Post Office Box 1892, Houston, TX 77251-1892, USA. Queller@rice.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12511650" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Altruism ; Animals ; Cell Adhesion ; Cell Adhesion Molecules/*genetics/*physiology ; Cell Communication ; Dictyostelium/*genetics/*physiology ; *Genes, Protozoan ; Mutation ; Protozoan Proteins/*genetics/*physiology ; Selection, Genetic ; Social Behavior ; Spores, Protozoan/physiology
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  • 168
    Publication Date: 2003-10-04
    Description: Agriculturally advantageous reduction in plant height is usually achieved by blocking the action or production of gibberellins. Here, we describe a different dwarfing mechanism found in maize brachytic2 (br2) mutants characterized by compact lower stalk internodes. The height reduction in these plants results from the loss of a P-glycoprotein that modulates polar auxin transport in the maize stalk. The sorghum ortholog of br2 is dwarf3 (dw3), an unstable mutant of long-standing commercial interest and concern. A direct duplication within the dw3 gene is responsible for its mutant nature and also for its instability, because it facilitates unequal crossing-over at the locus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Multani, Dilbag S -- Briggs, Steven P -- Chamberlin, Mark A -- Blakeslee, Joshua J -- Murphy, Angus S -- Johal, Gurmukh S -- New York, N.Y. -- Science. 2003 Oct 3;302(5642):81-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pioneer Hi-Bred International, 7250 Northwest 62nd Avenue, Johnston, IA 50131, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526073" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Biological Transport ; Cloning, Molecular ; Crossing Over, Genetic ; Gene Duplication ; *Genes, Plant ; Genes, Recessive ; Indoleacetic Acids/*metabolism ; Light ; Molecular Sequence Data ; Mutation ; P-Glycoproteins/chemistry/*genetics/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Plant Stems/cytology/metabolism ; Poaceae/cytology/genetics/growth & development/*metabolism ; Recombination, Genetic ; Zea mays/cytology/genetics/growth & development/*metabolism
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  • 169
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-06-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eastman, Quinn -- New York, N.Y. -- Science. 2003 Jun 20;300(5627):1858.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12817113" target="_blank"〉PubMed〈/a〉
    Keywords: Expert Testimony ; *Genetic Predisposition to Disease ; Genetic Testing ; Great Britain ; Humans ; Infant ; Infanticide/*legislation & jurisprudence ; Jurisprudence ; Long QT Syndrome/genetics ; Mitochondrial Diseases/genetics ; Mutation ; Risk Factors ; Sudden Infant Death/*etiology/*genetics
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  • 170
    Publication Date: 2003-01-11
    Description: Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heinrich, Michael C -- Corless, Christopher L -- Duensing, Anette -- McGreevey, Laura -- Chen, Chang-Jie -- Joseph, Nora -- Singer, Samuel -- Griffith, Diana J -- Haley, Andrea -- Town, Ajia -- Demetri, George D -- Fletcher, Christopher D M -- Fletcher, Jonathan A -- New York, N.Y. -- Science. 2003 Jan 31;299(5607):708-10. Epub 2003 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Department of Pathology, Oregon Health & Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA. heinrich@ohsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12522257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Chromosome Aberrations ; Cricetinae ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Exons ; Gastrointestinal Neoplasms/*genetics/metabolism ; Humans ; Karyotyping ; Mitogen-Activated Protein Kinases/metabolism ; Mutation ; Oncogenes ; Phosphorylation ; *Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-kit/*genetics/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/*genetics/metabolism ; STAT1 Transcription Factor ; STAT3 Transcription Factor ; Signal Transduction ; Trans-Activators/metabolism
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  • 171
    Publication Date: 2003-02-22
    Description: Genetic modification of mosquitoes offers exciting possibilities for controlling malaria, but success will depend on how transformation affects the fitness of modified insects. The expression of an exogenous gene, the mutations caused by its insertion, and inbreeding while transformed lines are established can all lead to reductions in fitness. Factors influencing fitness were investigated in cage experiments with four lines of transgenic Anopheles stephensi, a vector species of human malaria. The results indicate direct costs of the introduced transgene in at least three out of the four lines, as well as an apparent cost of the inbreeding involved in making transgenic homozygotes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Catteruccia, Flaminia -- Godfray, H Charles J -- Crisanti, Andrea -- New York, N.Y. -- Science. 2003 Feb 21;299(5610):1225-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, SAF Building, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12595691" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Genetically Modified/physiology ; Anopheles/*genetics/*physiology ; Crosses, Genetic ; DNA Transposable Elements ; Female ; Gene Frequency ; Genes, Insect ; Genes, Recessive ; Genetic Drift ; Genetics, Population ; Green Fluorescent Proteins ; Heterozygote ; Homozygote ; Inbreeding ; Luminescent Proteins/analysis/genetics ; Male ; Models, Genetic ; Mutation ; Oviposition ; Transformation, Genetic ; *Transgenes
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  • 172
    Publication Date: 2003-09-13
    Description: Stem cell self-renewal can be specified by local signals from the surrounding microenvironment, or niche. However, the relation between the niche and the mechanisms that ensure the correct balance between stem cell self-renewal and differentiation is poorly understood. Here, we show that dividing Drosophila male germline stem cells use intracellular mechanisms involving centrosome function and cortically localized Adenomatous Polyposis Coli tumor suppressor protein to orient mitotic spindles perpendicular to the niche, ensuring a reliably asymmetric outcome in which one daughter cell remains in the niche and self-renews stem cell identity, whereas the other, displaced away, initiates differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamashita, Yukiko M -- Jones, D Leanne -- Fuller, Margaret T -- 1P01 DK53074/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 12;301(5639):1547-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12970569" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Arabidopsis Proteins ; Cadherins/metabolism ; Calcium-Binding Proteins/*metabolism ; Cell Count ; Cell Differentiation ; *Cell Division ; Cell Polarity ; Centrosome/*physiology ; Cytoskeletal Proteins/metabolism ; Drosophila/*cytology/genetics/physiology ; Drosophila Proteins/*metabolism ; Germ Cells/cytology/*physiology ; Homeodomain Proteins/genetics/physiology ; Male ; Mutation ; Spindle Apparatus/physiology ; Stem Cells/cytology/*physiology ; Testis/cytology ; Trans-Activators/metabolism ; Tubulin/metabolism ; Tumor Suppressor Proteins/*metabolism ; beta Catenin
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  • 173
    Publication Date: 2003-07-12
    Description: Thrombin bound to platelets contributes to stop bleeding and, in pathological conditions, may cause vascular thrombosis. We have determined the structure of platelet glycoprotein Ibalpha (GpIbalpha) bound to thrombin at 2.3 angstrom resolution and defined two sites in GpIbalpha that bind to exosite II and exosite I of two distinct alpha-thrombin molecules, respectively. GpIbalpha occupancy may be sequential, as the site binding to alpha-thrombin exosite I appears to be cryptic in the unoccupied receptor but exposed when a first thrombin molecule is bound through exosite II. These interactions may modulate alpha-thrombin function by mediating GpIbalpha clustering and cleavage of protease-activated receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celikel, Reha -- McClintock, Richard A -- Roberts, James R -- Mendolicchio, G Loredana -- Ware, Jerry -- Varughese, Kottayil I -- Ruggeri, Zaverio M -- HL-31950/HL/NHLBI NIH HHS/ -- HL-42846/HL/NHLBI NIH HHS/ -- HL-48728/HL/NHLBI NIH HHS/ -- HL-55375/HL/NHLBI NIH HHS/ -- R01 HL042846/HL/NHLBI NIH HHS/ -- RR0833/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 11;301(5630):218-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Thrombosis and Hemostasis, 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/12855810" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Blood Coagulation ; Blood Platelets/chemistry/metabolism ; Crystallization ; Crystallography, X-Ray ; Fibrinogen/metabolism ; Humans ; Hydrogen Bonding ; Ligands ; Models, Molecular ; Mutation ; Platelet Aggregation ; Platelet Glycoprotein GPIb-IX Complex/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Tertiary ; Recombinant Proteins/chemistry/metabolism ; Thrombin/*chemistry/*metabolism
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  • 174
    Publication Date: 2003-04-19
    Description: Insulin receptors are abundant in the central nervous system, but their roles remain elusive. Here we show that the insulin receptor functions in axon guidance. The Drosophila insulin receptor (DInR) is required for photoreceptor-cell (R-cell) axons to find their way from the retina to the brain during development of the visual system. DInR functions as a guidance receptor for the adapter protein Dock/Nck. This function is independent of Chico, the Drosophila insulin receptor substrate (IRS) homolog.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Jianbo -- Wu, Lingling -- Chen, Zun -- Kohanski, Ronald A -- Pick, Leslie -- New York, N.Y. -- Science. 2003 Apr 18;300(5618):502-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brookdale Department for Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12702880" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Axons/*physiology ; Binding Sites ; Blotting, Western ; Brain/cytology/growth & development ; Carrier Proteins/genetics/immunology/metabolism/*physiology ; Cell Differentiation ; Cell Size ; Drosophila/genetics/*growth & development/physiology ; Drosophila Proteins/genetics/metabolism ; Eye/cytology/growth & development ; Female ; Growth Cones/physiology ; Insulin Receptor Substrate Proteins ; *Intracellular Signaling Peptides and Proteins ; Male ; Mutation ; Nerve Tissue Proteins/chemistry/genetics/metabolism ; Photoreceptor Cells, Invertebrate/cytology/*physiology ; Precipitin Tests ; Protein-Tyrosine Kinases/genetics/immunology/metabolism/*physiology ; *Receptor Protein-Tyrosine Kinases ; Receptor, Insulin/genetics/immunology/metabolism/*physiology ; Retina/cytology/growth & development ; Signal Transduction ; Two-Hybrid System Techniques ; Visual Pathways ; src Homology Domains
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  • 175
    Publication Date: 2003-10-25
    Description: Interferon-gamma (IFN-gamma) provides an essential component of immunity to tuberculosis by activating infected host macrophages to directly inhibit the replication of Mycobacterium tuberculosis (Mtb). IFN-gamma-inducible nitric oxide synthase 2 (NOS2) is considered a principal effector mechanism, although other pathways may also exist. Here, we identify one member of a newly emerging 47-kilodalton (p47) guanosine triphosphatase family, LRG-47, that acts independently of NOS2 to protect against disease. Mice lacking LRG-47 failed to control Mtb replication, unlike those missing the related p47 guanosine triphosphatases IRG-47 or IGTP. Defective bacterial killing in IFN-gamma-activated LRG-47-/- macrophages was associated with impaired maturation of Mtb-containing phagosomes, vesicles that otherwise recruited LRG-47 in wild-type cells. Thus, LRG-47 may serve as a critical vacuolar trafficking component used to dispose of intracellular pathogens like Mtb.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacMicking, John D -- Taylor, Gregory A -- McKinney, John D -- R01 A1051702/PHS HHS/ -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):654-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Infection Biology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. macmicj@mail.rockefeller.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Computational Biology ; Disease Susceptibility ; Female ; GTP Phosphohydrolases/genetics/physiology ; GTP-Binding Proteins/genetics/*physiology ; Hydrogen-Ion Concentration ; Immunity, Innate ; Interferon-gamma/*immunology ; Macrophage Activation ; Macrophages/immunology/metabolism ; Macrophages, Alveolar/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Mycobacterium tuberculosis/*growth & development ; Nitric Oxide Synthase/genetics/metabolism ; Nitric Oxide Synthase Type II ; Oligonucleotide Array Sequence Analysis ; Phagosomes/microbiology/physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Tuberculosis/*immunology/microbiology
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  • 176
    Publication Date: 2003-01-11
    Description: Mutations in DKC1 cause dyskeratosis congenita (DC), a disease characterized by premature aging and increased tumor susceptibility. The DKC1 protein binds to the box H + ACA small nucleolar RNAs and the RNA component of telomerase. Here we show that hypomorphic Dkc1 mutant (Dkc1m) mice recapitulate in the first and second generations (G1 and G2) the clinical features of DC. Dkc1m cells from G1 and G2 mice were impaired in ribosomal RNA pseudouridylation before the onset of disease. Reductions of telomere length in Dkc1m mice became evident only in later generations. These results suggest that deregulated ribosome function is important in the initiation of DC, whereas telomere shortening may modify and/or exacerbate DC.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruggero, Davide -- Grisendi, Silvia -- Piazza, Francesco -- Rego, Eduardo -- Mari, Francesca -- Rao, Pulivarthi H -- Cordon-Cardo, Carlos -- Pandolfi, Pier Paolo -- New York, N.Y. -- Science. 2003 Jan 10;299(5604):259-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12522253" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia ; Animals ; Apoptosis ; Bone Marrow Cells ; Cell Cycle Proteins/*genetics/*physiology ; Colony-Forming Units Assay ; Disease Models, Animal ; Dyskeratosis Congenita/complications/*genetics/*metabolism ; Female ; Genetic Predisposition to Disease ; Hematopoietic Stem Cells/physiology ; In Situ Hybridization, Fluorescence ; Male ; Mice ; Mutation ; Neoplasms/*etiology ; Nuclear Proteins/*genetics/*physiology ; Pseudouridine/*metabolism ; RNA, Ribosomal/*metabolism ; Ribosomes/physiology ; Telomerase/metabolism ; Telomere/metabolism/ultrastructure
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  • 177
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-07-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Engelberg-Kulka, Hanna -- Hazan, Ronen -- New York, N.Y. -- Science. 2003 Jul 25;301(5632):467-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel. hanita@cc.huji.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12881556" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Bacillus subtilis/genetics/metabolism/*physiology ; Bacterial Proteins/genetics/*metabolism ; Bacteriolysis ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Models, Biological ; Mutation ; *Operon ; Sigma Factor/genetics/metabolism ; Signal Transduction ; Spores, Bacterial/*physiology ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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  • 178
    Publication Date: 2003-10-04
    Description: Nitric oxide (NO) serves as a signal in plants. An Arabidopsis mutant (Atnos1) was identified that had impaired NO production, organ growth, and abscisic acid-induced stomatal movements. Expression of AtNOS1 with a viral promoter in Atnos1 mutant plants resulted in overproduction of NO. Purified AtNOS1 protein used the substrates arginine and nicotinamide adenine dinucleotide phosphate and was activated by Ca2+ and calmodulin-like mammalian endothelial nitric oxide synthase and neuronal nitric oxide synthase, yet it is a distinct enzyme with no sequence similarities to any mammalian isoform. Thus, AtNOS1 encodes a distinct nitric oxide synthase that regulates growth and hormonal signaling in plants.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Fang-Qing -- Okamoto, Mamoru -- Crawford, Nigel M -- GM 40672/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 3;302(5642):100-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526079" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*pharmacology ; Amino Acid Sequence ; Arabidopsis/*enzymology/*genetics/growth & development ; Arabidopsis Proteins/chemistry/*genetics/isolation & purification/*metabolism ; Enzyme Inhibitors/pharmacology ; Genes, Plant ; Kinetics ; Light ; Molecular Sequence Data ; Mutation ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/*metabolism ; Nitric Oxide Donors/pharmacology ; Nitric Oxide Synthase/chemistry/*genetics/isolation & purification/*metabolism ; Nitroprusside/pharmacology ; Plant Epidermis/drug effects/physiology ; Plant Leaves/enzymology/growth & development/physiology ; Plant Roots/growth & development ; Plant Shoots/growth & development ; *Signal Transduction
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  • 179
    Publication Date: 2003-08-30
    Description: Leishmania infections involve an acute phase of replication within macrophages, typically associated with pathology. After recovery parasites persist for long periods, which can lead to severe disease upon reactivation. Unlike the role of host factors, parasite factors affecting persistence are poorly understood. Leishmania major lacking phosphoglycans (lpg2-) were unable to survive in sand flies and macrophages, but retained the ability to persist indefinitely in the mammalian host without inducing disease. The L. major lpg2- thus provides a platform for probing parasite factors implicated in persistence and its role in disease and immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spath, Gerald F -- Lye, Lon-Fey -- Segawa, Hiroaki -- Sacks, David L -- Turco, Salvatore J -- Beverley, Stephen M -- AI31078/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 29;301(5637):1241-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University Medical School, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12947201" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Complement System Proteins/immunology ; Cytokines/physiology ; Female ; Glycosphingolipids/genetics/*physiology ; Host-Parasite Interactions ; Humans ; Insect Vectors/parasitology ; Leishmania major/genetics/pathogenicity/*physiology ; Leishmaniasis, Cutaneous/immunology/*parasitology/pathology ; Macrophage Activation ; Macrophages/*parasitology ; Membrane Proteins/genetics/*physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation ; Nitric Oxide/physiology ; Phagosomes/parasitology ; Phlebotomus/*parasitology ; Protozoan Proteins/genetics/physiology ; Virulence
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  • 180
    Publication Date: 2003-06-14
    Description: Comparison of the gene-expression profiles between adults of Drosophila melanogaster and Drosophila simulans has uncovered the evolution of genes that exhibit sex-dependent regulation. Approximately half the genes showed differences in expression between the species, and among these, approximately 83% involved a gain, loss, increase, decrease, or reversal of sex-biased expression. Most of the interspecific differences in messenger RNA abundance affect male-biased genes. Genes that differ in expression between the species showed functional clustering only if they were sex-biased. Our results suggest that sex-dependent selection may drive changes in expression of many of the most rapidly evolving genes in the Drosophila transcriptome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ranz, Jose M -- Castillo-Davis, Cristian I -- Meiklejohn, Colin D -- Hartl, Daniel L -- New York, N.Y. -- Science. 2003 Jun 13;300(5626):1742-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805547" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bayes Theorem ; Drosophila/*genetics ; Drosophila melanogaster/*genetics ; *Evolution, Molecular ; Female ; *Gene Expression ; Gene Expression Profiling ; Genes, Insect ; *Genome ; Male ; Mutation ; Nucleic Acid Hybridization ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/genetics/metabolism ; Selection, Genetic ; Sex Characteristics ; Species Specificity ; *Transcription, Genetic ; X Chromosome/genetics
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  • 181
    Publication Date: 2003-03-01
    Description: Carbonylated proteins were visualized in single cells of the budding yeast Saccharomyces cerevisiae, revealing that they accumulate with replicative age. Furthermore, carbonylated proteins were not inherited by daughter cells during cytokinesis. Mother cells of a yeast strain lacking the sir2 gene, a life-span determinant, failed to retain oxidatively damaged proteins during cytokinesis. These findings suggest that a genetically determined, Sir2p-dependent asymmetric inheritance of oxidatively damaged proteins may contribute to free-radical defense and the fitness of newborn cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aguilaniu, Hugo -- Gustafsson, Lena -- Rigoulet, Michel -- Nystrom, Thomas -- New York, N.Y. -- Science. 2003 Mar 14;299(5613):1751-3. Epub 2003 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Molecular Biology-Microbiology, Goteborg University, Goteborg, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610228" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; *Cell Division ; Genes, Fungal ; Histone Deacetylases/genetics/physiology ; Hydrogen Peroxide/metabolism ; Immunohistochemistry ; Mitochondria/metabolism ; Mutation ; Oxidation-Reduction ; *Oxidative Stress ; Paraquat/pharmacology ; Reactive Oxygen Species/metabolism ; Saccharomyces cerevisiae/cytology/genetics/metabolism/*physiology ; Saccharomyces cerevisiae Proteins/*metabolism ; Silent Information Regulator Proteins, Saccharomyces ; cerevisiae/genetics/physiology ; Sirtuin 2 ; Sirtuins/genetics/physiology ; Superoxides/metabolism
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  • 182
    Publication Date: 2003-05-10
    Description: Here we report an approach, based on antibody phage display, to generate molecular conformation sensors. Recombinant antibodies specific to the guanosine triphosphate (GTP)-bound conformation of the small guanosine triphosphatase (GTPase) Rab6, a regulator of membrane traffic, were generated and used to locate Rab6.GTP in fixed cells, and, after green fluorescent protein (GFP) tagging and intracellular expression, to follow Rab6.GTP in vivo. Rab6 was in its GTP-bound conformation on the Golgi apparatus and transport intermediates, and the geometry of transport intermediates was modulated by Rab6 activity. More generally, the same approach could be applied to other molecules that can be locked in a particular conformation in vitro.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nizak, Clement -- Monier, Solange -- del Nery, Elaine -- Moutel, Sandrine -- Goud, Bruno -- Perez, Franck -- New York, N.Y. -- Science. 2003 May 9;300(5621):984-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR144, Institut Curie, 26 rue d'Ulm, F75248 Paris Cedex 05, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12738866" target="_blank"〉PubMed〈/a〉
    Keywords: *Antibodies/chemistry/immunology/metabolism ; Bacterial Proteins ; Endoplasmic Reticulum/chemistry ; Fluorescent Antibody Technique ; Golgi Apparatus/*chemistry ; Green Fluorescent Proteins ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/*metabolism ; HeLa Cells ; Humans ; Immunoglobulin Variable Region ; Luminescent Proteins ; Mutation ; Peptide Library ; Protein Conformation ; Recombinant Fusion Proteins/analysis/chemistry/metabolism ; Recombinant Proteins/chemistry/immunology/metabolism ; Transfection ; Transport Vesicles/chemistry ; rab GTP-Binding Proteins/*analysis/chemistry/*immunology/metabolism
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  • 183
    Publication Date: 2003-03-22
    Description: Gibberellin (GA) regulates growth and development in plants. We isolated and characterized a rice GA-insensitive dwarf mutant, gid2. The GID2 gene encodes a putative F-box protein, which interacted with the rice Skp1 homolog in a yeast two-hybrid assay. In gid2, a repressor for GA signaling, SLR1, was highly accumulated in a phosphorylated form and GA increased its concentration, whereas SLR1 was rapidly degraded by GA through ubiquitination in the wild type. We conclude that GID2 is a positive regulator of GA signaling and that regulated degradation of SLR1 is initiated through GA-dependent phosphorylation and finalized by an SCF(GID2)-proteasome pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasaki, Akie -- Itoh, Hironori -- Gomi, Kenji -- Ueguchi-Tanaka, Miyako -- Ishiyama, Kanako -- Kobayashi, Masatomo -- Jeong, Dong-Hoon -- An, Gynheung -- Kitano, Hidemi -- Ashikari, Motoyuki -- Matsuoka, Makoto -- New York, N.Y. -- Science. 2003 Mar 21;299(5614):1896-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BioScience Center, Nagoya University, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12649483" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Codon, Terminator ; Enzyme Induction ; Genes, Plant ; Gibberellins/*metabolism/pharmacology ; Ligases/metabolism ; Molecular Sequence Data ; Mutation ; Open Reading Frames ; Oryza/genetics/growth & development/*metabolism ; Peptide Hydrolases/metabolism ; Phenotype ; Phosphorylation ; Plant Proteins/chemistry/*genetics/*metabolism ; *Proteasome Endopeptidase Complex ; Protein Structure, Tertiary ; Seeds/metabolism ; *Signal Transduction ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases ; alpha-Amylases/biosynthesis
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  • 184
    Publication Date: 2003-01-18
    Description: The global predominance of three clonal Toxoplasma gondii lineages suggests that they are endowed with an exceptional trait responsible for their current parasitism of nearly all warm-blooded vertebrates. Genetic polymorphism analyses indicate that these clonal lineages emerged within the last 10,000 years after a single genetic cross. Comparison with ancient strains (approximately 1 million years) suggests that the success of the clonal lineages resulted from the concurrent acquisition of direct oral infectivity. This key adaptation circumvented sexual recombination, simultaneously promoting transmission through successive hosts, hence leading to clonal expansion. Thus, changes in complex life cycles can occur rapidly and can profoundly influence pathogenicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, C -- Evans, D -- Cole, R H -- Kissinger, J C -- Ajioka, J W -- Sibley, L D -- New York, N.Y. -- Science. 2003 Jan 17;299(5605):414-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12532022" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cats ; DNA, Ribosomal/genetics ; DNA, Ribosomal Spacer/genetics ; Food Parasitology ; *Genes, Protozoan ; Introns ; Life Cycle Stages ; Mice ; Molecular Sequence Data ; Mouth ; Mutation ; Phylogeny ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Recombination, Genetic ; Reproduction ; *Selection, Genetic ; Toxoplasma/*genetics/pathogenicity/*physiology ; Toxoplasmosis/*parasitology/transmission ; Toxoplasmosis, Animal/*parasitology/transmission ; Virulence
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  • 185
    Publication Date: 2003-01-11
    Description: Atrial fibrillation (AF) is a common cardiac arrhythmia whose molecular etiology is poorly understood. We studied a family with hereditary persistent AF and identified the causative mutation (S140G) in the KCNQ1 (KvLQT1) gene on chromosome 11p15.5. The KCNQ1 gene encodes the pore-forming alpha subunit of the cardiac I(Ks) channel (KCNQ1/KCNE1), the KCNQ1/KCNE2 and the KCNQ1/KCNE3 potassium channels. Functional analysis of the S140G mutant revealed a gain-of-function effect on the KCNQ1/KCNE1 and the KCNQ1/KCNE2 currents, which contrasts with the dominant negative or loss-of-function effects of the KCNQ1 mutations previously identified in patients with long QT syndrome. Thus, the S140G mutation is likely to initiate and maintain AF by reducing action potential duration and effective refractory period in atrial myocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Yi-Han -- Xu, Shi-Jie -- Bendahhou, Said -- Wang, Xiao-Liang -- Wang, Ying -- Xu, Wen-Yuan -- Jin, Hong-Wei -- Sun, Hao -- Su, Xiao-Yan -- Zhuang, Qi-Nan -- Yang, Yi-Qing -- Li, Yue-Bin -- Liu, Yi -- Xu, Hong-Ju -- Li, Xiao-Fei -- Ma, Ning -- Mou, Chun-Ping -- Chen, Zhu -- Barhanin, Jacques -- Huang, Wei -- New York, N.Y. -- Science. 2003 Jan 10;299(5604):251-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiology, Tongji Hospital, and Institute of Medical Genetics, Tongji University, 399 Xin Cun Road, Shanghai 200065, People's Republic of China. drchen@public7.sta.net.cn〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12522251" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Adolescent ; Adult ; Aged ; Animals ; Atrial Fibrillation/*genetics/physiopathology ; COS Cells ; Child ; China ; Chromosomes, Human, Pair 11/genetics ; Electrocardiography ; Female ; Haplotypes ; Heart Atria/physiopathology ; Heart Ventricles/physiopathology ; Humans ; KCNQ Potassium Channels ; KCNQ1 Potassium Channel ; Lod Score ; Long QT Syndrome/genetics/physiopathology ; Male ; Microsatellite Repeats ; Middle Aged ; Mutation ; *Mutation, Missense ; Myocytes, Cardiac/*physiology ; Patch-Clamp Techniques ; Pedigree ; Potassium Channels/*genetics/physiology ; *Potassium Channels, Voltage-Gated
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  • 186
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alward, Wallace L M -- New York, N.Y. -- Science. 2003 Mar 7;299(5612):1527-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology and Visual Sciences, University of Iowa College of Medicine, Iowa City, IA 52242, USA. wallace-alward@uiowa.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12624251" target="_blank"〉PubMed〈/a〉
    Keywords: Albinism, Ocular/genetics ; Animals ; Anterior Eye Segment/*abnormalities ; Aryl Hydrocarbon Hydroxylases/genetics ; Cornea/abnormalities ; Cytochrome P-450 CYP1B1 ; *DNA-Binding Proteins ; Female ; Forkhead Transcription Factors ; Glaucoma/*congenital/*genetics/pathology/therapy ; Humans ; *Intraocular Pressure ; Iris/abnormalities ; Levodopa/administration & dosage/metabolism ; Mice ; Monophenol Monooxygenase/*deficiency/metabolism ; Mutation ; Optic Nerve ; Pregnancy ; Trabecular Meshwork/abnormalities/physiology ; Transcription Factors/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 187
    Publication Date: 2003-01-11
    Description: Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naive T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hori, Shohei -- Nomura, Takashi -- Sakaguchi, Shimon -- New York, N.Y. -- Science. 2003 Feb 14;299(5609):1057-61. Epub 2003 Jan 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunopathology, Research Center for Allergy and Immunology, Institute for Physical and Chemical Research, Yokohama 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12522256" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/analysis ; Autoimmune Diseases/immunology/prevention & control ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/biosynthesis ; DNA-Binding Proteins/genetics/*metabolism ; Forkhead Transcription Factors ; Gastritis/immunology/prevention & control ; *Immune Tolerance ; Inflammatory Bowel Diseases/immunology/prevention & control ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Mice, Transgenic ; Mutation ; Receptors, Antigen, T-Cell/immunology ; Receptors, Interleukin-2/analysis ; Recombinant Fusion Proteins/metabolism ; Self Tolerance ; T-Lymphocyte Subsets/cytology/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/*immunology/*metabolism ; Thymus Gland/cytology/metabolism ; Transduction, 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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  • 188
    Publication Date: 2011-08-24
    Description: Through the application of advanced technologies and mission concepts, architectures for missions beyond Earth orbit have been dramatically simplified. These concepts enable a stepping stone approach to science driven; technology enabled human and robotic exploration. Numbers and masses of vehicles required are greatly reduced, yet the pursuit of a broader range of science objectives is enabled. The scope of human missions considered range from the assembly and maintenance of large aperture telescopes for emplacement at the Sun-Earth libration point L2, to human missions to asteroids, the moon and Mars. The vehicle designs are developed for proof of concept, to validate mission approaches and understand the value of new technologies. The stepping stone approach employs an incremental buildup of capabilities, which allows for future decision points on exploration objectives. It enables testing of technologies to achieve greater reliability and understanding of costs for the next steps in exploration. c2003 American Institute of Aeronautics and Astronautics. Published by Elsevier Science Ltd. All rights reserved.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Acta astronautica (ISSN 0094-5765); Volume 53; 4-10; 387-97
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  • 189
    Publication Date: 2011-08-24
    Description: Remote sensing of the surface of Europa with near-infrared instruments has suggested the presence of hydrated materials, including sulfate salts. Attention has been focused on these salts for the information they might yield regarding the evolution of a putative interior ocean, and the evaluation of its astrobiological potential. These materials exhibit distinct infrared absorption features due to bound water. The interactions of this water with the host molecules lead to fine structure that can be used to discriminate among these materials on the basis of their spectral behavior. This fine structure is even more pronounced at the low temperatures prevalent on icy satellites. Examination of hydrated sulfate salt spectra measured under cryogenic temperature conditions provides realistic constraints for future remote-sensing missions to Europa. In particular, it suggests that a spectrometer system capable of 2-5 nm spectral resolution or better, with a spatial resolution approaching 100 m, would be able to differentiate among proposed hydrated surface materials, if present, and constrain their distributions across the surface. Such information would provide valuable insights into the evolutionary history of Europa.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Astrobiology (ISSN 1531-1074); Volume 3; 4; 771-84
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  • 190
    Publication Date: 2011-08-24
    Description: Human missions to Mars are planned to happen within this century. Activities associated therewith will interact with the environment of Mars in two reciprocal ways: (i) the mission needs to be protected from the natural environmental elements that can be harmful to human health, the equipment or to their operations; (ii) the specific natural environment of Mars should be protected so that it retains its value for scientific and other purposes. The following environmental elements need to be considered in order to protect humans and the equipment on the planetary surface: (i) cosmic ionizing radiation, (ii) solar particle events; (iii) solar ultraviolet radiation; (iv) reduced gravity; (v) thin atmosphere; (vi) extremes in temperatures and their fluctuations; and (vii) surface dust. In order to protect the planetary environment, the requirements for planetary protection as adopted by COSPAR for lander missions need to be revised in view of human presence on the planet. Landers carrying equipment for exobiological investigations require special consideration to reduce contamination by terrestrial microorganisms and organic matter to the greatest feasible extent. Records of human activities on the planet's surface should be maintained in sufficient detail that future scientific experimenters can determine whether environmental modifications have resulted from explorations. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Advances in space research : the official journal of the Committee on Space Research (COSPAR); Volume 31; 1; 87-95
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  • 191
    Publication Date: 2011-08-24
    Description: Obtaining in situ chemical data from planetary bodies such as Mars or Europa can present significant challenges. The one analytical technique that has many of the requisite characteristics to meet such a challenge is electroanalysis. Described here are three electroanalytical devices designed for in situ geochemical and biological analysis on Mars. The Mars Environmental Compatibility Assessment (MECA) was built and flight qualified for the now cancelled NASA Mars 2001 Lander. Part of MECA consisted of four "cells" containing arrays of electrochemical based sensors for measuring the ionic species in soil samples. A next-generation MECA, the Robotic Chemical Analysis Laboratory (RCAL), uses a carousel-type system to allow for greater customization of analytical procedures. A second instrument, proposed as part of the 2007 CryoScout mission, consists of a flow-through inorganic chemical analyzer (MICA). CryoScout is a torpedo-like device designed for subsurface investigation of the stratigraphic climate record embedded in Mars' north polar cap. As the CryoScout melts its way through the ice cap, MICA will collect and analyze the meltwater for a variety of inorganics and chemical parameters. By analyzing the chemistry locked in the layers of dust, salt, and ice, geologists will be able to determine the recent history of climate, water, and atmosphere on Mars and link it to the past. Finally, electroanalysis shows its abilities in the detection of possible microorganism on Mars or elsewhere in the solar system. To identify an unknown microorganism, one that may not even use Earth-type biochemistry, requires a detection scheme which makes minimal assumptions and looks for the most general features. Recent work has demonstrated that the use of an array of electrochemical sensors which monitors the changes in a solution via electrical conductivity, pH, and ion selective electrodes, can be used to detect minute chemical perturbations caused by the growth of bacteria and with the correct methodology provide unamibiguous detection of such life forms.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Chemphyschem : a European journal of chemical physics and physical chemistry (ISSN 1439-4235); Volume 4; 2; 162-8
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  • 192
    Publication Date: 2011-08-24
    Description: The results of a study of ion-molecule reactions occurring in pure methane, acetylene, ethylene, ethane, propyne, propene, propane, and diacetylene at pressures up to 40 microns of pressure are reported. A variety of experimental methods are used: The standard double resonance in an ICR, for determination of the precursor ions and the modulated double resonance ejection in an ICR, for the determination of the daughter ions. The FA-SIFT technique was used for validation and examination of termolecular reactions with rate coefficients that are less than 10(-26) cm(6) s(-1). An extensive database of reaction kinetics already exists for many of these reactions. The main point of this study was the determination of the accuracy of this database and to search for any missing reactions and reaction channels that may have been omitted from earlier investigations. A specific objective of this work was to extend the study to the highest pressures possible to find out if there were any important termolecular reaction channels occurring. A new approach was used here. In the pure hydrocarbon gases the mass spectra were followed as a function of the pressure changes of the gas. An initial guess was first made using the current literature as a source of the reaction kinetics that were expected. A model of the ion abundances was produced from the solution of the partial differential equations in terms of reaction rate coefficients and initial abundances. The experimental data was fitted to the model for all of the pressures by a least squares minimization to the reaction rate coefficients and initial abundances. The reaction rate coefficients obtained from the model were then compared to the literature values. Several new channels and reactions were discovered when the modeled fits were compared to the actual data. This is all explained in the text and the implications of these results are discussed for the Titan atmosphere.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Journal of the American Society for Mass Spectrometry (ISSN 1044-0305); Volume 14; 8; 900-15
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  • 193
    Publication Date: 2011-08-24
    Description: Automation and Robotics (A&R) systems are a key technology for Mars exploration. All over the world initiatives in this field aim at developing new A&R systems and technologies for planetary surface exploration. From December 2000 to February 2002 Kayser-Threde GmbH, Munich, Germany lead a study called AROMA (Automation and Robotics for Human Mars Exploration) under ESA contract in order to define a reference architecture of A&R elements in support of a human Mars exploration program. One of the goals of this effort is to initiate new developments and to maintain the competitiveness of European industry within this field. c2003 Published by Elsevier Science Ltd.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Acta astronautica (ISSN 0094-5765); Volume 53; 4-10; 399-404
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  • 194
    Publication Date: 2004-12-03
    Description: Oblique impacts are the norm rather than the exception for impact craters on planetary surfaces. This work focuses on the excavation of experimental oblique impact craters using the NASA Ames Vertical Gun Range (AVGR). Three-dimensional particle image velocimetry (3D PIV) is used to obtain quantitative data on ejection positions, three dimensional velocities and angles. These data are then used to constrain Maxwell's Z Model and follow the subsurface evolution of the excavation-stage flow-field center during oblique impacts.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Impact Cratering: Bridging the Gap Between Modeling and Observations; 9; LPI-Contrib-1155
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  • 195
    Publication Date: 2005-04-13
    Description: This presentation will outline a proposed mission for the Jupiter Icy Moons Orbiter (JIMO). The mission outlined will concentrate on an examination of Europa. Some of the primary science goals for the JIMO mission are: 1) to answer broad science questions, 2) improved knowledge of Jovian system; specifically, lunar geological and geophysical properties, 3) chemical composition of Jovian lunar surfaces and subterranean matter, and 4) the search for life. In order to address these issues, the experiment proposed here will deploy orbiting, surface, and subterranean science platforms.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Forum on Concepts and Approaches for Jupiter Icy Moons Orbiter; 30; LPI-Contrib-1163
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  • 196
    Publication Date: 2005-04-01
    Description: This paper presents a discussion on scientific goals for Jupiter's atmosphere which include near and middle infrared remote sensing capabilities and high resolution spectroscopy.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Forum on Concepts and Approaches for Jupiter Icy Moons Orbiter; 59; LPI-Contrib-1163
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  • 197
    Publication Date: 2004-10-30
    Description: Following the Galileo spacecraft encounters with Europa, Ganymede, and Callisto, evidence emerged suggesting that these Galilean moons of Jupiter may have liquid oceans underneath their icy shells. Detection of the oceans on one or all three moons will have profound implications on probability of life beyond the Earth. The icy satellites also have tidal environments that are among the strongest in the solar system. The leading time-varying tidal forcing term on the surface of Europa is at least 9 times larger than those on the inner planets. Tidal forcing on the surfaces of Ganymede and Callisto are about 10% and 7%, respectively, of that on Europa. Since a planetary body with internal fluid deforms more than an otherwise solid body, tidal measurements offer exciting opportunities to detect the oceans.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Forum on Concepts and Approaches for Jupiter Icy Moons Orbiter; 88; LPI-Contrib-1163
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  • 198
    Publication Date: 2004-10-30
    Description: A Jupiter atmospheric entry probe as part of JIMO is a cost effective way to address fundamental science questions identified in the National Research Council Solar System Exploration Decadal Survey (SSEDS): New Frontiers in the Solar System, An Integrated Ex- ploration Strategy. Compared to either the cost of an entirely separate Jupiter mission, or the cost of JIMO itself, inclusion of such a probe on JIMO would be cost advantageous. The probe itself could be relatively simple, and could build on the Galileo Probe heritage. The SSEDS specifically identified the distribution of water across the Solar System as a Key Scientific Question. Correspondingly, knowing the water abun dance on Jupiter is fundamental to understanding almost every aspect of the evolution of the early solar nebula. The Galileo Probe obtained the abundance of several key elements in Jupiter's atmosphere, which data have already caused major rethinking of theories of how Jupiter formed and how the early solar nebula evolved. However, because of a combination of circumstances, the global abundance of the key element oxygen, in the form of water, was not obtained. Without knowledge of the jovian water abundance, further progress in understanding Solar System evolution and planet formation will be greatly inhibited. Therefore, quantifying jovian water abundance should be a goal of the very next mission to the jovian system. Such a measurement would be impossible via remote sensing from the JIMO orbiter because of the large distances the JIMO orbiter maintains from Jupiter. A Jupiter atmospheric entry probe as part of JIMO could achieve the fundamental water measurement. In order that a probe avoid repeating the Galileo probe's experience of failing to obtain the jovian water abundance, the probe should go deep, to at least 100 bars pressure. Probes to 100 bars have been accomplished many times in descending to the surface of Venus, and at 100 bars the temperature of the jovian atmosphere is 60-70 K less than the surface temperature of Venus.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Forum on Concepts and Approaches for Jupiter Icy Moons Orbiter; 90; LPI-Contrib-1163
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  • 199
    Publication Date: 2004-10-30
    Description: The Galileo Solid State Imaging (SSI) experiment provided high-resolution images of Europa's surface allowing identification of surface features barely distinguishable at Voyager's resolution. SSI revealed the visible pitting on Europa's surface to be due to large disrupted features, chaos, and smaller sub-circular patches, lenticulae. Chaos features contain a hummocky matrix material and commonly contain dislocated blocks of ridged plains. Lenticulae are morphologically interrelated and can be divided into three classes: domes, spots, and micro-chaos. Domes are broad, upwarped features that generally do not disrupt the texture of the ridged plains. Spots are areas of low albedo that are generally smooth in texture compared to other units. Micro-chaos are disrupted features with a hummocky matrix material, resembling that observed within chaos regions. Chaos and lenticulae are ubiquitous in the SSI regional map observations, which average approximately 200 meters per pixel (m/pxl) in resolution, and appear in several of the ultra-high resolution, i.e., better than 50 m/pxl, images of Europa as well. SSI also provided a number of multi-spectral observations of chaos and lenticulae. Using this dataset we have undertaken a thorough study of the morphology, size, spacing, stratigraphy, and color of chaos and lenticulae to determine their properties and evaluate models of their formation. Geological mapping indicates that chaos and micro-chaos have a similar internal morphology of in-situ degradation suggesting that a similar process was operating during their formation. The size distribution denotes a dominant size of 4-8 km in diameter for features containing hummocky material (i.e., chaos and micro-chaos). Results indicate a dominant spacing of 15 - 36 km apart. Chaos and lenticulae are generally among the youngest features stratigraphically observed on the surface, suggesting a recent change in resurfacing style. Also, the reddish non-icy materials on Europa's surface have high concentrations in many chaos and lenticulae features. Nonetheless, a complete global map of the distribution of chaos and lenticulae is not possible with the SSI dataset. Only 〈20% of the surface has been imaged at 200 m/pxl or better resolution, mostly of the near-equatorial regions. Color and ultra-high-res images have much less surface coverage. Thus we suggest that full global imaging of Europa at 200 m/pxl or better resolution, preferably in multi-spectral wavelengths, should be a high priority for the JIMO mission.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Forum on Concepts and Approaches for Jupiter Icy Moons Orbiter; 79; LPI-Contrib-1163
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  • 200
    Publication Date: 2004-10-30
    Description: Imaging radars with wavelengths in the range of 10 cm to 1 m can deeply penetrate the surface of an icy body, revealing details of the geomorphology, local structure, and electrical properties of the upper layers. Radar studies of icy surfaces on Earth have used the polarization state of backscatter echoes at multiple frequencies to characterize the surface and subsurface properties of glaciers, showing relatively smooth surfaces on the scale of radar wave-lengths, and subsurface scattering from volume scatterers consistent with ice pipes and lenses. These volume scattering effects are evident in enhanced polarization ratios over a limited range of backscatter incidence angles. The Galilean satellites exhibit similarly enhanced polarization ratios and volumetric scattering effects, but the observations are limited in angular resolution, leading to ambiguity in interpreting the scattering mechanisms and their structural implications.
    Keywords: Lunar and Planetary Science and Exploration
    Type: Forum on Concepts and Approaches for Jupiter Icy Moons Orbiter; 65; LPI-Contrib-1163
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