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  • Amino Acid Sequence  (2,910)
  • Cells, Cultured  (1,353)
  • American Association for the Advancement of Science (AAAS)  (4,136)
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  • 1
    Publication Date: 2002-03-23
    Description: Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFalpha has the opposite effects. Thus, the continual presence of TNFalpha is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beattie, Eric C -- Stellwagen, David -- Morishita, Wade -- Bresnahan, Jacqueline C -- Ha, Byeong Keun -- Von Zastrow, Mark -- Beattie, Michael S -- Malenka, Robert C -- DA00439/DA/NIDA NIH HHS/ -- MH063394/MH/NIMH NIH HHS/ -- NS 31193/NS/NINDS NIH HHS/ -- NS38079/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 22;295(5563):2282-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA. beattie.2@osu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11910117" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/pharmacology ; Astrocytes/*metabolism ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Gene Expression Regulation/drug effects ; Hippocampus/cytology/metabolism ; Neuronal Plasticity/drug effects ; Neurons/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/metabolism ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type I ; Synapses/drug effects/*metabolism ; Synaptic Transmission/drug effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors/*metabolism
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" 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/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
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  • 3
    Publication Date: 2002-12-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funes, Soledad -- Davidson, Edgar -- Reyes-Prieto, Adrian -- Magallon, Susana -- Herion, Pascal -- King, Michael P -- Gonzalez-Halphen, Diego -- HL59646/HL/NHLBI NIH HHS/ -- TW01176/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2155.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico (UNAM), 04510 D.F., Mexico.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481129" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apicomplexa/enzymology/*genetics/ultrastructure ; *Biological Evolution ; Cell Nucleus/genetics ; Chlamydomonas reinhardtii/enzymology/genetics ; Chlorophyta/enzymology/*genetics ; Cloning, Molecular ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/chemistry/*genetics ; *Gene Transfer, Horizontal ; Genes ; Genes, Protozoan ; Molecular Sequence Data ; Phylogeny ; Plastids/*genetics ; Symbiosis ; Toxoplasma/enzymology/genetics
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  • 4
    Publication Date: 2002-02-09
    Description: Double-stranded RNA-mediated gene interference (RNAi) in Caenorhabditis elegans systemically inhibits gene expression throughout the organism. To investigate how gene-specific silencing information is transmitted between cells, we constructed a strain that permits visualization of systemic RNAi. We used this strain to identify systemic RNA interference-deficient (sid) loci required to spread gene-silencing information between tissues but not to initiate or maintain an RNAi response. One of these loci, sid-1, encodes a conserved protein with predicted transmembrane domains. SID-1 is expressed in cells sensitive to RNAi, is localized to the cell periphery, and is required cell-autonomously for systemic RNAi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winston, William M -- Molodowitch, Christina -- Hunter, Craig P -- New York, N.Y. -- Science. 2002 Mar 29;295(5564):2456-9. Epub 2002 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834782" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/embryology/*genetics/metabolism ; Caenorhabditis elegans Proteins/chemistry/*genetics/*physiology ; Calmodulin-Binding Proteins/genetics ; Cytoplasm/metabolism ; Embryo, Nonmammalian/physiology ; *Gene Silencing ; Genes, Helminth ; Germ Cells/metabolism ; Green Fluorescent Proteins ; Intestines/metabolism ; Luminescent Proteins/genetics ; Membrane Proteins/chemistry/*genetics/*physiology ; Molecular Sequence Data ; Mosaicism ; Muscle Proteins/genetics ; Muscles/metabolism ; Mutation ; Protein Structure, Tertiary ; RNA, Double-Stranded/*genetics/metabolism ; RNA, Helminth/*genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Transgenes
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-08-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ingolia, Nicholas T -- Murray, Andrew W -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):948-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology and Bauer Center for Genomics Research, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12169717" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; Biological Evolution ; *Cell Cycle Proteins ; Cells, Cultured ; Dual Specificity Phosphatase 1 ; *Feedback, Physiological ; Immediate-Early Proteins/*metabolism ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; *Phosphoprotein Phosphatases ; Platelet-Derived Growth Factor/metabolism/pharmacology ; Protein Phosphatase 1 ; Protein Tyrosine Phosphatases/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2003-04-26
    Description: Tubular nanostructures are suggested to have a wide range of applications in nanotechnology. We report our observation of the self-assembly of a very short peptide, the Alzheimer's beta-amyloid diphenylalanine structural motif, into discrete and stiff nanotubes. Reduction of ionic silver within the nanotubes, followed by enzymatic degradation of the peptide backbone, resulted in the production of discrete nanowires with a long persistence length. The same dipeptide building block, made of D-phenylalanine, resulted in the production of enzymatically stable nanotubes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reches, Meital -- Gazit, Ehud -- New York, N.Y. -- Science. 2003 Apr 25;300(5619):625-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12714741" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Amyloid beta-Peptides/chemistry ; Biosensing Techniques ; Birefringence ; Dipeptides/*chemistry ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Molecular Sequence Data ; *Nanotechnology ; Oxidation-Reduction ; Protein Conformation ; Silver ; Solubility ; Spectroscopy, Fourier Transform Infrared
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  • 7
    Publication Date: 2002-02-09
    Description: The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gadek, T R -- Burdick, D J -- McDowell, R S -- Stanley, M S -- Marsters, J C Jr -- Paris, K J -- Oare, D A -- Reynolds, M E -- Ladner, C -- Zioncheck, K A -- Lee, W P -- Gribling, P -- Dennis, M S -- Skelton, N J -- Tumas, D B -- Clark, K R -- Keating, S M -- Beresini, M H -- Tilley, J W -- Presta, L G -- Bodary, S C -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1086-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834839" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/pharmacology ; Cyclosporine/pharmacology ; Dermatitis, Irritant/drug therapy ; Dinitrofluorobenzene ; Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Immunosuppressive Agents/chemical synthesis/chemistry/metabolism/*pharmacology ; Intercellular Adhesion Molecule-1/chemistry/*immunology/*metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Mutagenesis ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thiophenes/*chemical synthesis/chemistry/metabolism/*pharmacology ; beta-Alanine/analogs & derivatives/*chemical ; synthesis/chemistry/metabolism/*pharmacology
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  • 8
    Publication Date: 2002-02-09
    Description: Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rezaie, Tayebeh -- Child, Anne -- Hitchings, Roger -- Brice, Glen -- Miller, Lauri -- Coca-Prados, Miguel -- Heon, Elise -- Krupin, Theodore -- Ritch, Robert -- Kreutzer, Donald -- Crick, R Pitts -- Sarfarazi, Mansoor -- EY-09947/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1077-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834836" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alternative Splicing ; Amino Acid Sequence ; Brain/metabolism ; Chromosome Mapping ; Chromosomes, Human, Pair 10/genetics ; Ciliary Body/metabolism ; Exons ; Eye Proteins/analysis/chemistry/*genetics/physiology ; Female ; Glaucoma, Open-Angle/*genetics ; Golgi Apparatus/chemistry ; Heterozygote ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; *Mutation ; *Mutation, Missense ; Nerve Tissue Proteins/analysis/chemistry/*genetics/physiology ; Ocular Hypertension/genetics ; Pedigree ; Polymorphism, Single-Stranded Conformational ; Retina/metabolism ; Trabecular Meshwork/metabolism ; *Transcription Factor TFIIIA ; Zinc Fingers
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  • 9
    Publication Date: 2002-04-27
    Description: Little is known of how plant disease resistance (R) proteins recognize pathogens and activate plant defenses. Rcr3 is specifically required for the function of Cf-2, a Lycopersicon pimpinellifolium gene bred into cultivated tomato (Lycopersicon esculentum) for resistance to Cladosporium fulvum. Rcr3 encodes a secreted papain-like cysteine endoprotease. Genetic analysis shows Rcr3 is allelic to the L. pimpinellifolium Ne gene, which suppresses the Cf-2-dependent autonecrosis conditioned by its L. esculentum allele, ne (necrosis). Rcr3 alleles from these two species encode proteins that differ by only seven amino acids. Possible roles of Rcr3 in Cf-2-dependent defense and autonecrosis are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kruger, Julia -- Thomas, Colwyn M -- Golstein, Catherine -- Dixon, Mark S -- Smoker, Matthew -- Tang, Saijun -- Mulder, Lonneke -- Jones, Jonathan D G -- New York, N.Y. -- Science. 2002 Apr 26;296(5568):744-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Sainsbury Laboratory, John Innes Centre, Norwich NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11976458" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Base Sequence ; Cladosporium/*physiology ; Cloning, Molecular ; Cysteine Endopeptidases/chemistry/*genetics/*metabolism ; Cysteine Proteinase Inhibitors/pharmacology ; Gene Expression Regulation, Plant ; *Genes, Plant ; Immunity, Innate ; Leucine/analogs & derivatives/pharmacology ; Lycopersicon esculentum/*enzymology/genetics/*microbiology/physiology ; Molecular Sequence Data ; Mutation ; Phenotype ; *Plant Diseases ; Plant Leaves/enzymology ; Plant Proteins/*metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/chemistry/metabolism ; Tobacco/genetics ; Transgenes
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gallo, Robert C -- New York, N.Y. -- Science. 2002 Nov 29;298(5599):1728-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12459576" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Serodiagnosis/history ; Acquired Immunodeficiency Syndrome/diagnosis/*history/immunology/virology ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Cells, Cultured ; France ; *HIV/classification/isolation & purification/physiology ; History, 20th Century ; Human T-lymphotropic virus 1/isolation & purification/physiology ; Human T-lymphotropic virus 2/isolation & purification/physiology ; Humans ; Interleukin-2/history/isolation & purification/physiology ; Patents as Topic/history ; RNA-Directed DNA Polymerase/history/isolation & purification/metabolism ; United States ; Virus Cultivation
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  • 11
    Publication Date: 2002-04-06
    Description: The conserved Sir2 family of proteins has protein deacetylase activity that is dependent on NAD (the oxidized form of nicotinamide adenine dinucleotide). Although histones are one likely target for the enzymatic activity of eukaryotic Sir2 proteins, little is known about the substrates and roles of prokaryotic Sir2 homologs. We reveal that an archaeal Sir2 homolog interacts specifically with the major archaeal chromatin protein, Alba, and that Alba exists in acetylated and nonacetylated forms. Furthermore, we show that Sir2 can deacetylate Alba and mediate transcriptional repression in a reconstituted in vitro transcription system. These data provide a paradigm for how Sir2 family proteins influence transcription and suggest that modulation of chromatin structure by acetylation arose before the divergence of the archaeal and eukaryotic lineages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, Stephen D -- Botting, Catherine H -- Wardleworth, Benjamin N -- Jackson, Stephen P -- White, Malcolm F -- New York, N.Y. -- Science. 2002 Apr 5;296(5565):148-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Cancer Cell Unit, The Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2QH, UK. sdb@mole.bio.cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11935028" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Amino Acid Sequence ; Archaeal Proteins/*chemistry/*metabolism ; Chromatin/*metabolism ; DNA/metabolism ; Gene Expression Regulation, Archaeal ; Histone Deacetylases/chemistry/*metabolism ; Molecular Sequence Data ; Molecular Weight ; Protein Binding ; Recombinant Fusion Proteins/chemistry/metabolism ; *Silent Information Regulator Proteins, Saccharomyces cerevisiae ; Sirtuin 2 ; Sirtuins ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sulfolobus/*chemistry/genetics/metabolism ; Templates, Genetic ; Trans-Activators/chemistry/*metabolism ; Transcription, Genetic
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  • 12
    Publication Date: 2003-04-12
    Description: Rapid turnover of the tumor suppressor protein p53 requires the MDM2 ubiquitin ligase, and both interact with p300-CREB-binding protein transcriptional coactivator proteins. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grossman, Steven R -- Deato, Maria E -- Brignone, Chrystelle -- Chan, Ho Man -- Kung, Andrew L -- Tagami, Hideaki -- Nakatani, Yoshihiro -- Livingston, David M -- CA15751/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):342-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690203" target="_blank"〉PubMed〈/a〉
    Keywords: Adenovirus E1A Proteins/metabolism ; Animals ; Catalysis ; Cells, Cultured ; E1A-Associated p300 Protein ; Embryo, Mammalian ; Fibroblasts/metabolism ; Humans ; Ligases/antagonists & inhibitors/metabolism ; Mice ; Nuclear Proteins/antagonists & inhibitors/*metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; Trans-Activators/antagonists & inhibitors/*metabolism ; Transfection ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/*metabolism ; Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-02-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Calladine, C R -- Pratap, V -- Chandran, V -- Mizuguchi, K -- Luisi, B F -- New York, N.Y. -- Science. 2003 Jan 31;299(5607):661-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12561825" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry ; Glycine/chemistry ; Ion Channels/*chemistry ; *Models, Molecular ; Protein Conformation ; Protein Structure, Secondary
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2003-03-01
    Description: Although curvature of biological surfaces has been considered from mathematical and biophysical perspectives, its molecular and developmental basis is unclear. We have studied the cin mutant of Antirrhinum, which has crinkly rather than flat leaves. Leaves of cin display excess growth in marginal regions, resulting in a gradual introduction of negative curvature during development. This reflects a change in the shape and the progression of a cell-cycle arrest front moving from the leaf tip toward the base. CIN encodes a TCP protein and is expressed downstream of the arrest front. We propose that CIN promotes zero curvature (flatness) by making cells more sensitive to an arrest signal, particularly in marginal regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nath, Utpal -- Crawford, Brian C W -- Carpenter, Rosemary -- Coen, Enrico -- New York, N.Y. -- Science. 2003 Feb 28;299(5611):1404-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12610308" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antirrhinum/cytology/*genetics/*growth & development/metabolism ; Base Sequence ; Cell Cycle ; Cell Differentiation ; Cell Division ; Cell Size ; Cyclin D3 ; Cyclins/genetics/metabolism ; Gene Deletion ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Histones/genetics/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutation ; Plant Leaves/anatomy & histology/cytology/*growth & development/metabolism ; Plant Proteins/chemistry/genetics/metabolism ; Surface Properties ; Transcription Factors/chemistry/genetics/*metabolism
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  • 15
    Publication Date: 2003-06-14
    Description: In eukaryotes, the combinatorial association of sequence-specific DNA binding proteins is essential for transcription. We have used protein arrays to test 492 pairings of a nearly complete set of coiled-coil strands from human basic-region leucine zipper (bZIP) transcription factors. We find considerable partnering selectivity despite the bZIPs' homologous sequences. The interaction data are of high quality, as assessed by their reproducibility, reciprocity, and agreement with previous observations. Biophysical studies in solution support the relative binding strengths observed with the arrays. New associations provide insights into the circadian clock and the unfolded protein response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newman, John R S -- Keating, Amy E -- New York, N.Y. -- Science. 2003 Jun 27;300(5628):2097-101. Epub 2003 Jun 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12805554" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Basic-Leucine Zipper Transcription Factors ; Chromatography, High Pressure Liquid ; Circadian Rhythm ; Circular Dichroism ; Cyclic AMP Response Element-Binding Protein/chemistry/metabolism ; DNA-Binding Proteins/chemistry/isolation & purification/*metabolism ; Dimerization ; G-Box Binding Factors ; Humans ; *Leucine Zippers ; Peptides/chemistry/isolation & purification/metabolism ; *Protein Array Analysis ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Signal Transduction ; Temperature ; Thermodynamics ; Transcription Factors/*chemistry/isolation & purification/*metabolism
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  • 16
    Publication Date: 2003-07-05
    Description: Raf kinases have been linked to endothelial cell survival. Here, we show that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) differentially activate Raf, resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature. bFGF activated Raf-1 via p21-activated protein kinase-1 (PAK-1) phosphorylation of serines 338 and 339, resulting in Raf-1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis, independent of the mitogen-activated protein kinase kinase-1 (MEK1). In contrast, VEGF activated Raf-1 via Src kinase, leading to phosphorylation of tyrosines 340 and 341 and MEK1-dependent protection from extrinsic-mediated apoptosis. These findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alavi, Alireza -- Hood, John D -- Frausto, Ricardo -- Stupack, Dwayne G -- Cheresh, David A -- CA45726/CA/NCI NIH HHS/ -- CA50286/CA/NCI NIH HHS/ -- CA75924/CA/NCI NIH HHS/ -- P01 CA78045/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Jul 4;301(5629):94-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, 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/12843393" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Cell Survival ; Cells, Cultured ; Chick Embryo ; Endothelial Growth Factors/pharmacology ; Endothelium, Vascular/*cytology/drug effects ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Fibroblast Growth Factor 2/pharmacology ; Flavonoids/pharmacology ; Humans ; Intercellular Signaling Peptides and Proteins/pharmacology ; Lymphokines/pharmacology ; MAP Kinase Kinase 1 ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Neovascularization, Pathologic ; *Neovascularization, Physiologic/drug effects ; Phosphorylation ; Point Mutation ; Protein Transport ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins B-raf ; Proto-Oncogene Proteins c-raf/chemistry/genetics/*metabolism ; Signal Transduction ; Umbilical Veins ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; p21-Activated Kinases ; src-Family Kinases/antagonists & inhibitors/metabolism
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  • 17
    Publication Date: 2003-07-19
    Description: We collected and completely sequenced 28,469 full-length complementary DNA clones from Oryza sativa L. ssp. japonica cv. Nipponbare. Through homology searches of publicly available sequence data, we assigned tentative protein functions to 21,596 clones (75.86%). Mapping of the cDNA clones to genomic DNA revealed that there are 19,000 to 20,500 transcription units in the rice genome. Protein informatics analysis against the InterPro database revealed the existence of proteins presented in rice but not in Arabidopsis. Sixty-four percent of our cDNAs are homologous to Arabidopsis proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rice Full-Length cDNA Consortium -- National Institute of Agrobiological Sciences Rice Full-Length cDNA Project Team -- Kikuchi, Shoshi -- Satoh, Kouji -- Nagata, Toshifumi -- Kawagashira, Nobuyuki -- Doi, Koji -- Kishimoto, Naoki -- Yazaki, Junshi -- Ishikawa, Masahiro -- Yamada, Hitomi -- Ooka, Hisako -- Hotta, Isamu -- Kojima, Keiichi -- Namiki, Takahiro -- Ohneda, Eisuke -- Yahagi, Wataru -- Suzuki, Kohji -- Li, Chao Jie -- Ohtsuki, Kenji -- Shishiki, Toru -- Foundation of Advancement of International Science Genome Sequencing & Analysis Group -- Otomo, Yasuhiro -- Murakami, Kazuo -- Iida, Yoshiharu -- Sugano, Sumio -- Fujimura, Tatsuto -- Suzuki, Yutaka -- Tsunoda, Yuki -- Kurosaki, Takashi -- Kodama, Takeko -- Masuda, Hiromi -- Kobayashi, Michie -- Xie, Quihong -- Lu, Min -- Narikawa, Ryuya -- Sugiyama, Akio -- Mizuno, Kouichi -- Yokomizo, Satoko -- Niikura, Junko -- Ikeda, Rieko -- Ishibiki, Junya -- Kawamata, Midori -- Yoshimura, Akemi -- Miura, Junichirou -- Kusumegi, Takahiro -- Oka, Mitsuru -- Ryu, Risa -- Ueda, Mariko -- Matsubara, Kenichi -- RIKEN -- Kawai, Jun -- Carninci, Piero -- Adachi, Jun -- Aizawa, Katsunori -- Arakawa, Takahiro -- Fukuda, Shiro -- Hara, Ayako -- Hashizume, Wataru -- Hayatsu, Norihito -- Imotani, Koichi -- Ishii, Yoshiyuki -- Itoh, Masayoshi -- Kagawa, Ikuko -- Kondo, Shinji -- Konno, Hideaki -- Miyazaki, Ai -- Osato, Naoki -- Ota, Yoshimi -- Saito, Rintaro -- Sasaki, Daisuke -- Sato, Kenjiro -- Shibata, Kazuhiro -- Shinagawa, Akira -- Shiraki, Toshiyuki -- Yoshino, Masayasu -- Hayashizaki, Yoshihide -- Yasunishi, Ayako -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):376-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, National Institute of Agrobiological Sciences, 2-1-2 Kannon-dai, Tsukuba, Ibaraki 305-8602, Japan. skikuchi@nias.affrc.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869764" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing ; Amino Acid Sequence ; Cloning, Molecular ; Computational Biology ; DNA, Complementary ; Databases, Nucleic Acid ; Databases, Protein ; Genes, Plant ; *Genome, Plant ; Molecular Sequence Data ; Open Reading Frames ; Oryza/*genetics ; Plant Proteins/chemistry/genetics/physiology ; Protein Structure, Tertiary ; RNA, Antisense/genetics ; *Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; Sequence Homology, Nucleic Acid ; Transcription Factors/chemistry/genetics ; Transcription, Genetic
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  • 18
    Publication Date: 2003-11-01
    Description: Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Wen G -- Chang, Qiang -- Lin, Yingxi -- Meissner, Alexander -- West, Anne E -- Griffith, Eric C -- Jaenisch, Rudolf -- Greenberg, Michael E -- HD 18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):885-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/*genetics ; Calcium/*metabolism ; Cell Membrane/physiology ; Cells, Cultured ; *Chromosomal Proteins, Non-Histone ; Cloning, Molecular ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins/*metabolism ; Electrophoretic Mobility Shift Assay ; *Gene Expression Regulation ; Gene Silencing ; Histones/metabolism ; Methyl-CpG-Binding Protein 2 ; Methylation ; Mice ; Mice, Knockout ; Neurons/metabolism/physiology ; Phosphorylation ; Potassium Chloride/pharmacology ; Precipitin Tests ; Promoter Regions, Genetic ; Rats ; *Repressor Proteins ; Rett Syndrome/genetics ; *Transcription, Genetic
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  • 19
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: The metabotropic glutamate receptors (mGluRs) are widely distributed in the brain and play important roles in synaptic plasticity. Here it is shown that some types of mGluRs are activated not only by glutamate but also by extracellular Ca2+ (Ca2+o). A single amino acid residue was found to determine the sensitivity of mGluRs to Ca2+o. One of the receptors, mGluR1alpha, but not its point mutant with reduced sensitivity to Ca2+o, caused morphological changes when transfected into mammalian cells. Thus, the sensing of Ca2+o by mGluRs may be important in cells under physiological condition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kubo, Y -- Miyashita, T -- Murata, Y -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1722-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan. ykubo@tmin.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9497291" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/ultrastructure ; Amino Acid Sequence ; Animals ; Binding Sites ; Brain/metabolism ; CHO Cells ; Calcium/*metabolism/pharmacology ; Cell Size ; Cricetinae ; Cyclic AMP/metabolism ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; Glutamic Acid/metabolism/pharmacology ; Molecular Sequence Data ; Oocytes ; Point Mutation ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Rats ; Receptors, Metabotropic Glutamate/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Second Messenger Systems ; Transfection ; Xenopus laevis
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 20
    Publication Date: 1998-12-16
    Description: A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified alpha-DG protein. Soluble alpha-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, alpha-DG is a cellular receptor for both LCMV and LFV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cao, W -- Henry, M D -- Borrow, P -- Yamada, H -- Elder, J H -- Ravkov, E V -- Nichol, S T -- Compans, R W -- Campbell, K P -- Oldstone, M B -- AG 00080/AG/NIA NIH HHS/ -- AI 09484/AI/NIAID NIH HHS/ -- DK09712/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):2079-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Virology, Department of Neuropharmacology, The 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/9851928" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arenavirus/metabolism ; Cell Line ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; Dystroglycans ; Lassa virus/*metabolism/physiology ; Lymphocytic choriomeningitis virus/*metabolism/physiology ; Membrane Glycoproteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Receptors, Virus/chemistry/*metabolism ; Recombinant Fusion Proteins/metabolism ; Virus Replication
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  • 21
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-29
    Description: After the vertebrate lens is induced from head ectoderm, lens-specific genes are expressed. Transcriptional regulation of the lens-specific alphaA-crystallin gene is controlled by an enhancer element, alphaCE2. A gene encoding an alphaCE2-binding protein, L-maf(lens-specific maf), was isolated. L-maf expression is initiated in the lens placode and is restricted to lens cells. The gene product L-Maf regulates the expression of multiple genes expressed in the lens, and ectopic expression of this transcription factor converts chick embryonic ectodermal cells and cultured cells into lens fibers. Thus, vertebrate lens induction and differentiation can be triggered by the activation of L-Maf.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ogino, H -- Yasuda, K -- New York, N.Y. -- Science. 1998 Apr 3;280(5360):115-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0101, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9525857" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Basic-Leucine Zipper Transcription Factors ; Cell Differentiation ; Cells, Cultured ; Chick Embryo ; Crystallins/genetics ; DNA, Complementary ; DNA-Binding Proteins/chemistry/genetics ; Ectoderm ; Enhancer Elements, Genetic ; Eye Proteins/genetics ; G-Box Binding Factors ; *Gene Expression Regulation, Developmental ; Genes, Reporter ; Intermediate Filament Proteins/genetics ; Lens, Crystalline/*cytology/*embryology/metabolism ; Maf Transcription Factors ; Molecular Sequence Data ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic ; Transcriptional Activation ; Transfection
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Normile, D -- New York, N.Y. -- Science. 1998 Dec 11;282(5396):1975-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874644" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry/*methods ; Animals ; Blastocyst ; Cattle/embryology/*genetics ; Cell Differentiation ; Cells, Cultured ; *Cloning, Organism ; Embryo Transfer/veterinary ; Fallopian Tubes/cytology ; Female ; Japan ; *Nuclear Transfer Techniques ; Oocytes ; Ovarian Follicle/cytology ; Pregnancy
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 23
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: Mice homozygous for a disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype. When this allele is crossed into quasi-monoclonal (QM) mice, which have a very limited B cell repertoire, homozygotes have fewer somatic mutations at the immunoglobulin heavy chain and lambda chain loci than do heterozygotes or wild-type QM mice. That is, mismatch repair seems to contribute to somatic hypermutation rather than stifling it. It is suggested that at immunoglobulin loci in hypermutable B cells, mismatched base pairs are "corrected" according to the newly synthesized DNA strand, thereby fixing incipient mutations instead of eliminating them.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cascalho, M -- Wong, J -- Steinberg, C -- Wabl, M -- 1R01 GM37699/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 20;279(5354):1207-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0670, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9469811" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenosine Triphosphatases ; Alleles ; Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Base Composition ; Base Sequence ; Cloning, Molecular ; Crosses, Genetic ; *DNA Repair ; *DNA Repair Enzymes ; *DNA-Binding Proteins ; Female ; Gene Rearrangement ; *Genes, Immunoglobulin ; Heterozygote ; Immunoglobulin Heavy Chains/chemistry/genetics ; Immunoglobulin Variable Region/chemistry/*genetics ; Immunoglobulin lambda-Chains/chemistry/genetics ; Male ; Mice ; Mice, Knockout ; Molecular Sequence Data ; *Mutation ; Proteins/*genetics/physiology
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-10
    Description: The 2.5 angstrom resolution x-ray crystal structure of the Escherichia coli RNA polymerase (RNAP) alpha subunit amino-terminal domain (alphaNTD), which is necessary and sufficient to dimerize and assemble the other RNAP subunits into a transcriptionally active enzyme and contains all of the sequence elements conserved among eukaryotic alpha homologs, has been determined. The alphaNTD monomer comprises two distinct, flexibly linked domains, only one of which participates in the dimer interface. In the alphaNTD dimer, a pair of helices from one monomer interact with the cognate helices of the other to form an extensive hydrophobic core. All of the determinants for interactions with the other RNAP subunits lie on one face of the alphaNTD dimer. Sequence alignments, combined with secondary-structure predictions, support proposals that a heterodimer of the eukaryotic RNAP subunits related to Saccharomyces cerevisiae Rpb3 and Rpb11 plays the role of the alphaNTD dimer in prokaryotic RNAP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, G -- Darst, S A -- GM19441-01/GM/NIGMS NIH HHS/ -- GM53759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 10;281(5374):262-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9657722" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; DNA-Directed RNA Polymerases/*chemistry ; Dimerization ; Escherichia coli/*enzymology ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; RNA Polymerase II/chemistry ; *Saccharomyces cerevisiae Proteins ; Sequence Alignment
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  • 25
    Publication Date: 1998-12-18
    Description: CTLA-4, a negative regulator of T cell function, was found to associate with the T cell receptor (TCR) complex zeta chain in primary T cells. The association of TCRzeta with CTLA-4, reconstituted in 293 transfectants, was enhanced by p56(lck)-induced tyrosine phosphorylation. Coexpression of the CTLA-4-associated tyrosine phosphatase, SHP-2, resulted in dephosphorylation of TCRzeta bound to CTLA-4 and abolished the p56(lck)-inducible TCRzeta-CTLA-4 interaction. Thus, CTLA-4 inhibits TCR signal transduction by binding to TCRzeta and inhibiting tyrosine phosphorylation after T cell activation. These findings have broad implications for the negative regulation of T cell function and T cell tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, K M -- Chuang, E -- Griffin, M -- Khattri, R -- Hong, D K -- Zhang, W -- Straus, D -- Samelson, L E -- Thompson, C B -- Bluestone, J A -- P01 AI35294-6/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2263-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ben May Institute for Cancer Research, and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856951" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antigens, CD ; Antigens, Differentiation/*metabolism ; CTLA-4 Antigen ; Cell Line ; Cells, Cultured ; Humans ; *Immunoconjugates ; Intracellular Signaling Peptides and Proteins ; *Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics/metabolism ; Membrane Proteins/*metabolism ; Mice ; Mice, Inbred BALB C ; Models, Immunological ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/genetics/metabolism ; Receptors, Antigen, T-Cell/*metabolism ; Recombinant Fusion Proteins/metabolism ; SH2 Domain-Containing Protein Tyrosine Phosphatases ; *Signal Transduction ; T-Lymphocytes/*immunology ; Transfection ; src Homology Domains
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  • 26
    Publication Date: 1998-04-16
    Description: FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yeh, W C -- de la Pompa, J L -- McCurrach, M E -- Shu, H B -- Elia, A J -- Shahinian, A -- Ng, M -- Wakeham, A -- Khoo, W -- Mitchell, K -- El-Deiry, W S -- Lowe, S W -- Goeddel, D V -- Mak, T W -- CA13106/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1954-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, University of Toronto, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9506948" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Antigens, CD95/genetics/physiology ; *Apoptosis ; Carrier Proteins/genetics/*physiology ; Cell Transformation, Neoplastic ; Cells, Cultured ; Doxorubicin/pharmacology ; *Embryonic and Fetal Development ; Endothelium, Vascular/embryology ; Fas-Associated Death Domain Protein ; Female ; Gene Expression ; Gene Targeting ; Heart/*embryology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Oncogenes ; Receptors, Tumor Necrosis Factor/genetics/physiology ; Signal Transduction ; Tumor Necrosis Factor-alpha/pharmacology
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  • 27
    Publication Date: 1998-06-20
    Description: An efficient system for genetic modification and large-scale cloning of cattle is of importance for agriculture, biotechnology, and human medicine. Here, actively dividing fetal fibroblasts were genetically modified with a marker gene, a clonal line was selected, and the cells were fused to enucleated mature oocytes. Out of 28 embryos transferred to 11 recipient cows, three healthy, identical, transgenic calves were generated. Furthermore, the life-span of near senescent fibroblasts could be extended by nuclear transfer, as indicated by population doublings in fibroblast lines derived from a 40-day-old fetal clone. With the ability to extend the life-span of these primary cultured cells, this system would be useful for inducing complex genetic modifications in cattle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cibelli, J B -- Stice, S L -- Golueke, P J -- Kane, J J -- Jerry, J -- Blackwell, C -- Ponce de Leon, F A -- Robl, J M -- New York, N.Y. -- Science. 1998 May 22;280(5367):1256-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9596577" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Animals, Genetically Modified ; Blastocyst ; Cattle/embryology/*genetics ; Cell Aging ; Cell Division ; Cell Nucleus/genetics ; Cells, Cultured ; Clone Cells ; *Cloning, Organism ; Embryo Transfer ; Female ; Fetus/cytology ; Fibroblasts/*cytology ; G1 Phase ; Male ; Nuclear Transfer Techniques ; Oocytes/cytology ; Transfection ; Transgenes
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  • 28
    Publication Date: 1998-02-21
    Description: Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4, 5-trisphosphate [PtdIns(3,4,5)P3] and PtdIns(3,4)P2 in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr308-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P3 and associated with lipid vesicles containing it. These kinases contain an NH2-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, L -- Anderson, K -- Stokoe, D -- Erdjument-Bromage, H -- Painter, G F -- Holmes, A B -- Gaffney, P R -- Reese, C B -- McCormick, F -- Tempst, P -- Coadwell, J -- Hawkins, P T -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1998 Jan 30;279(5351):710-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Inositide Laboratory, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9445477" target="_blank"〉PubMed〈/a〉
    Keywords: 3-Phosphoinositide-Dependent Protein Kinases ; Alternative Splicing ; Amino Acid Sequence ; Animals ; Cell Line ; Cell Membrane/enzymology ; Cloning, Molecular ; DNA, Complementary ; Drosophila ; Drosophila Proteins ; Enzyme Activation ; Humans ; Liposomes/metabolism ; Molecular Sequence Data ; Open Reading Frames ; Phosphatidylinositol Phosphates/*metabolism ; Phosphorylation ; Platelet-Derived Growth Factor/pharmacology ; Protein-Serine-Threonine Kinases/chemistry/genetics/isolation & ; purification/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-akt ; Rats ; Recombinant Proteins/metabolism ; Sheep ; *Signal Transduction
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  • 29
    Publication Date: 1998-03-21
    Description: Viral infection is sometimes associated with the initiation or exacerbation of autoimmune disease, although the underlying mechanisms remain unclear. One proposed mechanism is that viral determinants that mimic host antigens trigger self-reactive T cell clones to destroy host tissue. An epitope expressed by a coat protein of herpes simplex virus-type 1 (HSV-1) KOS strain has now been shown to be recognized by autoreactive T cells that target corneal antigens in a murine model of autoimmune herpes stromal keratitis. Mutant HSV-1 viruses that lacked this epitope did not induce autoimmune disease. Thus, expression of molecular mimics can influence the development of autoimmune disease after viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhao, Z S -- Granucci, F -- Yeh, L -- Schaffer, P A -- Cantor, H -- AI 37562/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1344-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, and Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478893" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Autoantigens/immunology ; Autoimmune Diseases/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Capsid/chemistry/genetics/*immunology ; *Capsid Proteins ; Cornea/*immunology ; Epitopes ; Eye Proteins/immunology ; Herpesvirus 1, Human/*immunology ; Keratitis, Herpetic/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; *Molecular Mimicry ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligopeptides/immunology ; Viral Proteins
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in Escherichia coli. Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutaredoxin 1 (Grx1). The gene encoding Grx1 is regulated by OxyR, thus providing a mechanism for autoregulation. The redox potential of OxyR was determined to be -185 millivolts, ensuring that OxyR is reduced in the absence of stress. These results represent an example of redox signaling through disulfide bond formation and reduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, M -- Aslund, F -- Storz, G -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1718-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9497290" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/genetics/metabolism ; Base Sequence ; Cysteine/metabolism ; *DNA-Binding Proteins ; Disulfides/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins ; Gene Expression Regulation, Bacterial ; Glutaredoxins ; Glutathione/metabolism ; Glutathione Disulfide/metabolism ; Glutathione Reductase/metabolism ; Hydrogen Peroxide/*metabolism/pharmacology ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; *Oxidoreductases ; Proteins/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; Signal Transduction ; Thioredoxins/metabolism ; Transcription Factors/genetics/*metabolism
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  • 31
    Publication Date: 1998-10-23
    Description: Analysis of the 1,042,519-base pair Chlamydia trachomatis genome revealed unexpected features related to the complex biology of chlamydiae. Although chlamydiae lack many biosynthetic capabilities, they retain functions for performing key steps and interconversions of metabolites obtained from their mammalian host cells. Numerous potential virulence-associated proteins also were characterized. Several eukaryotic chromatin-associated domain proteins were identified, suggesting a eukaryotic-like mechanism for chlamydial nucleoid condensation and decondensation. The phylogenetic mosaic of chlamydial genes, including a large number of genes with phylogenetic origins from eukaryotes, implies a complex evolution for adaptation to obligate intracellular parasitism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, R S -- Kalman, S -- Lammel, C -- Fan, J -- Marathe, R -- Aravind, L -- Mitchell, W -- Olinger, L -- Tatusov, R L -- Zhao, Q -- Koonin, E V -- Davis, R W -- AI 39258/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1998 Oct 23;282(5389):754-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Infectious Diseases, University of California, Berkeley, CA 94720, USA. ctgenome@socrates.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9784136" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis ; Amino Acid Sequence ; Amino Acids/biosynthesis ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Proteins/chemistry/genetics ; Biological Evolution ; Chlamydia trachomatis/classification/*genetics/metabolism/physiology ; DNA Repair ; Energy Metabolism ; Enzymes/chemistry/genetics ; *Genome, Bacterial ; Humans ; Lipids/biosynthesis ; Molecular Sequence Data ; Peptidoglycan/biosynthesis/genetics ; Phylogeny ; Protein Biosynthesis ; Recombination, Genetic ; *Sequence Analysis, DNA ; Transcription, Genetic ; Transformation, Bacterial ; Virulence
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-10
    Description: Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5 positions of an alpha helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chemical properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye molecules added from outside the cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Griffin, B A -- Adams, S R -- Tsien, R Y -- NS27177/NS/NINDS NIH HHS/ -- T32 CA09523/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 10;281(5374):269-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0647, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9657724" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calmodulin/chemistry/genetics/metabolism ; Cell Membrane Permeability ; Cell Survival ; Cysteine/*chemistry ; Energy Transfer ; Ethylene Glycol ; Fluoresceins/chemical synthesis/chemistry/*metabolism ; Fluorescence ; *Fluorescent Dyes ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; Jurkat Cells ; Ligands ; Luminescent Proteins/chemistry/genetics/metabolism ; Molecular Sequence Data ; Organometallic Compounds/chemical synthesis/chemistry/*metabolism ; Peptides/chemistry/*metabolism ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/*metabolism ; Spectrometry, Fluorescence ; Transfection
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the central core of the enzyme to the carboxyl-terminal domain assumes a coiled-coil configuration and protrudes away from the remainder of the enzyme. The positively charged DNA-proximal surface of the linker makes only a few contacts with the DNA downstream of the cleavage site. In combination with the crystal structures of the reconstituted human topoisomerase I before and after DNA cleavage, this information suggests which amino acid residues are involved in catalyzing phosphodiester bond breakage and religation. The structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, L -- Redinbo, M R -- Qiu, X -- Hol, W G -- Champoux, J J -- CA65656/CA/NCI NIH HHS/ -- GM16713/GM/NIGMS NIH HHS/ -- GM49156/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1998 Mar 6;279(5356):1534-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biomolecular Structure Center and Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195-7742, USA. emerald_biostructures@rocketmail.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9488652" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arginine/chemistry/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; DNA/chemistry/*metabolism ; DNA Topoisomerases, Type I/*chemistry/*metabolism ; Humans ; Hydrogen Bonding ; *Models, Chemical ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/chemistry/metabolism ; *Protein Conformation ; Protein Structure, Secondary ; Tyrosine/chemistry/metabolism
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  • 34
    Publication Date: 1998-11-13
    Description: The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peschon, J J -- Slack, J L -- Reddy, P -- Stocking, K L -- Sunnarborg, S W -- Lee, D C -- Russell, W E -- Castner, B J -- Johnson, R S -- Fitzner, J N -- Boyce, R W -- Nelson, N -- Kozlosky, C J -- Wolfson, M F -- Rauch, C T -- Cerretti, D P -- Paxton, R J -- March, C J -- Black, R A -- CA43793/CA/NCI NIH HHS/ -- DK53804/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1281-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunex Corporation, Seattle, WA 98101, USA. peschon@immunex.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812885" target="_blank"〉PubMed〈/a〉
    Keywords: ADAM Proteins ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Cell Membrane/*metabolism ; Cells, Cultured ; Crosses, Genetic ; *Embryonic and Fetal Development ; L-Selectin/metabolism ; Ligands ; Membrane Proteins/*metabolism ; Metalloendopeptidases/chemistry/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Processing, Post-Translational ; Receptors, Tumor Necrosis Factor/metabolism ; Transforming Growth Factor alpha/metabolism ; Tumor Necrosis Factor-alpha/*metabolism
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  • 35
    Publication Date: 1998-03-21
    Description: Long-term potentiation (LTP) is an activity-dependent strengthening of synaptic efficacy that is considered to be a model of learning and memory. Protein tyrosine phosphorylation is necessary to induce LTP. Here, induction of LTP in CA1 pyramidal cells of rats was prevented by blocking the tyrosine kinase Src, and Src activity was increased by stimulation producing LTP. Directly activating Src in the postsynaptic neuron enhanced excitatory synaptic responses, occluding LTP. Src-induced enhancement of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptor-mediated synaptic responses required raised intracellular Ca2+ and N-methyl-D-aspartate (NMDA) receptors. Thus, Src activation is necessary and sufficient for inducing LTP and may function by up-regulating NMDA receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lu, Y M -- Roder, J C -- Davidow, J -- Salter, M W -- New York, N.Y. -- Science. 1998 Feb 27;279(5355):1363-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular and Medical Genetics, University of Toronto, M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9478899" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Electric Stimulation ; Enzyme Activation ; Excitatory Postsynaptic Potentials/drug effects ; Hippocampus/cytology/enzymology/*physiology ; In Vitro Techniques ; *Long-Term Potentiation ; Molecular Sequence Data ; Oligopeptides/pharmacology ; Patch-Clamp Techniques ; Peptide Fragments/pharmacology ; Proto-Oncogene Proteins pp60(c-src)/pharmacology ; Pyramidal Cells/enzymology/*physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Recombinant Proteins/pharmacology ; Up-Regulation ; src-Family Kinases/*metabolism
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Feb 13;279(5353):978-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9490484" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Crystallography, X-Ray ; Databases, Factual ; *Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry/classification/genetics ; Software
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Service, R F -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):578-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10328734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Electric Stimulation ; Electrodes ; Electrodes, Implanted ; *Electronics ; Electrophysiology ; Humans ; Nerve Net/*physiology ; Nervous System Diseases/*therapy ; Neurons/*physiology ; Rats ; Silicon ; *Transistors, Electronic
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: Genetic selection was exploited in combination with structure-based design to transform an intimately entwined, dimeric chorismate mutase into a monomeric, four-helix-bundle protein with near native activity. Successful reengineering depended on choosing a thermostable starting protein, introducing point mutations that preferentially destabilize the wild-type dimer, and using directed evolution to optimize an inserted interhelical turn. Contrary to expectations based on studies of other four-helix-bundle proteins, only a small fraction of possible turn sequences (fewer than 0.05 percent) yielded well-behaved, monomeric, and highly active enzymes. Selection for catalytic function thus provides an efficient yet stringent method for rapidly assessing correctly folded polypeptides and may prove generally useful for protein design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacBeath, G -- Kast, P -- Hilvert, D -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1958-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9506949" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Catalysis ; Chorismate Mutase/*chemistry/genetics/*metabolism ; Circular Dichroism ; Cloning, Molecular ; Dimerization ; *Directed Molecular Evolution ; Escherichia coli/genetics ; Models, Molecular ; Molecular Sequence Data ; *Protein Conformation ; *Protein Engineering ; Protein Folding ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/metabolism ; Transformation, Bacterial
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-07-31
    Description: Gamete interactions during fertilization exhibit species specificity. In abalone, the sperm protein lysin species-specifically creates a hole in the egg envelope. Lysin evolves rapidly by positive Darwinian selection. Evolution of the egg receptor for lysin provides the selective pressure for lysin's divergence. The egg receptor for lysin is a tandemly repeated sequence that evolves by concerted evolution. Concerted evolution in the egg receptor could explain the rapid, adaptive evolution in sperm lysin and may provide an underlying molecular mechanism that gives rise to species-specific fertilization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swanson, W J -- Vacquier, V D -- HD12986/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1998 Jul 31;281(5377):710-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093-0202, USA. jwswanson@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9685267" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Egg Proteins/chemistry/*genetics/metabolism ; *Evolution, Molecular ; Female ; Introns ; Male ; Molecular Sequence Data ; Mollusca/chemistry/*genetics/physiology ; Mucoproteins/chemistry/genetics/*metabolism ; Ovum/chemistry/physiology ; Receptors, Cell Surface/chemistry/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Sequence Alignment ; Species Specificity ; Sperm-Ovum Interactions ; Spermatozoa/chemistry/physiology ; Vitelline Membrane/*chemistry/metabolism
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-09
    Description: A "switch" mutant of the Arc repressor homodimer was constructed by interchanging the sequence positions of a hydrophobic core residue, leucine 12, and an adjacent surface polar residue, asparagine 11, in each strand of an intersubunit beta sheet. The mutant protein adopts a fold in which each beta strand is replaced by a right-handed helix and side chains in this region undergo significant repacking. The observed structural changes allow the protein to maintain solvent exposure of polar side chains and optimal burial of hydrophobic side chains. These results suggest that new protein folds can evolve from existing folds without drastic or large-scale mutagenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cordes, M H -- Walsh, N P -- McKnight, C J -- Sauer, R T -- AI-15706/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):325-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195898" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Asparagine/chemistry ; Circular Dichroism ; Hydrogen Bonding ; Leucine/chemistry ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; *Protein Folding ; *Protein Structure, Secondary ; Protein Structure, Tertiary ; Repressor Proteins/*chemistry ; Viral Proteins/*chemistry ; Viral Regulatory and Accessory Proteins
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  • 41
    Publication Date: 1999-10-09
    Description: The Yersinia pseudotuberculosis invasin protein promotes bacterial entry by binding to host cell integrins with higher affinity than natural substrates such as fibronectin. The 2.3 angstrom crystal structure of the invasin extracellular region reveals five domains that form a 180 angstrom rod with structural similarities to tandem fibronectin type III domains. The integrin-binding surfaces of invasin and fibronectin include similarly located key residues, but in the context of different folds and surface shapes. The structures of invasin and fibronectin provide an example of convergent evolution, in which invasin presents an optimized surface for integrin binding, in comparison with host substrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamburger, Z A -- Brown, M S -- Isberg, R R -- Bjorkman, P J -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):291-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 156-29, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514372" target="_blank"〉PubMed〈/a〉
    Keywords: *Adhesins, Bacterial ; Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Binding Sites ; Crystallography, X-Ray ; Evolution, Molecular ; Fibronectins/chemistry/metabolism ; Hydrogen Bonding ; Integrins/*metabolism ; Ligands ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Yersinia pseudotuberculosis/*chemistry/metabolism
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  • 42
    Publication Date: 1999-09-25
    Description: The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide libraries based on the calcineurin docking motif of NFAT. This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aramburu, J -- Yaffe, M B -- Lopez-Rodriguez, C -- Cantley, L C -- Hogan, P G -- Rao, A -- R01 AI 40127/AI/NIAID NIH HHS/ -- R01 GM056203/GM/NIGMS NIH HHS/ -- R01 HL 03601/HL/NHLBI NIH HHS/ -- R43 AI 43726/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2129-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10497131" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cell Nucleus/metabolism ; Cyclosporine/pharmacology ; Cytokines/biosynthesis/genetics ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/metabolism ; Gene Expression Regulation ; Genes, Reporter ; HeLa Cells ; Humans ; Immunosuppressive Agents/chemistry/metabolism/*pharmacology ; Jurkat Cells ; Molecular Sequence Data ; NFATC Transcription Factors ; *Nuclear Proteins ; Oligopeptides/chemistry/metabolism/*pharmacology ; Peptide Library ; Peptides/chemistry/metabolism/*pharmacology ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes/*drug effects/immunology ; Transcription Factors/*antagonists & inhibitors/chemistry/metabolism ; Transfection
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  • 43
    Publication Date: 1999-11-05
    Description: The Brca1 (breast cancer gene 1) tumor suppressor protein is phosphorylated in response to DNA damage. Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation. ATM resides in a complex with Brca1 and phosphorylated Brca1 in vivo and in vitro in a region that contains clusters of serine-glutamine residues. Phosphorylation of this domain appears to be functionally important because a mutated Brca1 protein lacking two phosphorylation sites failed to rescue the radiation hypersensitivity of a Brca1-deficient cell line. Thus, phosphorylation of Brca1 by the checkpoint kinase ATM may be critical for proper responses to DNA double-strand breaks and may provide a molecular explanation for the role of ATM in breast cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cortez, D -- Wang, Y -- Qin, J -- Elledge, S J -- GM44664/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1162-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Department of Cell 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/10550055" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Ataxia Telangiectasia/genetics ; Ataxia Telangiectasia Mutated Proteins ; BRCA1 Protein/*metabolism ; Breast Neoplasms/genetics ; Cell Cycle Proteins ; Cell Line ; *DNA Damage ; *DNA Repair ; DNA, Complementary ; DNA-Binding Proteins ; Female ; Gamma Rays ; Genes, BRCA1 ; Genetic Predisposition to Disease ; HeLa Cells ; Heterozygote ; Humans ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Tumor Suppressor Proteins
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, I -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):14-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9917254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/metabolism ; Cells, Cultured ; Dimerization ; Drug Design ; Humans ; Neurons/*metabolism ; Potassium Channels/metabolism ; Rats ; Receptors, GABA-B/*chemistry/*metabolism ; Signal Transduction ; gamma-Aminobutyric Acid/metabolism
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  • 45
    Publication Date: 1999-10-03
    Description: Precursors of alpha-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with alpha-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT-/-) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT-/- mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT-/- mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, C L -- Ouellette, A J -- Satchell, D P -- Ayabe, T -- Lopez-Boado, Y S -- Stratman, J L -- Hultgren, S J -- Matrisian, L M -- Parks, W C -- New York, N.Y. -- Science. 1999 Oct 1;286(5437):113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. wilson_c@kids.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10506557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Catalysis ; Cytoplasmic Granules/enzymology ; Escherichia coli/growth & development ; Escherichia coli Infections/immunology/microbiology ; Female ; Humans ; *Immunity, Innate ; *Immunity, Mucosal ; Intestinal Mucosa/enzymology/immunology/microbiology ; Intestine, Small/enzymology/*immunology/microbiology ; Male ; Matrix Metalloproteinase 7 ; Metalloendopeptidases/genetics/*metabolism ; Mice ; Molecular Sequence Data ; Paneth Cells/enzymology ; Protein Precursors/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Salmonella typhimurium/growth & development/pathogenicity ; Tissue Extracts/pharmacology
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-26
    Description: Katanin, a member of the AAA adenosine triphosphatase (ATPase) superfamily, uses nucleotide hydrolysis energy to sever and disassemble microtubules. Many AAA enzymes disassemble stable protein-protein complexes, but their mechanisms are not well understood. A fluorescence resonance energy transfer assay demonstrated that the p60 subunit of katanin oligomerized in an adenosine triphosphate (ATP)- and microtubule-dependent manner. Oligomerization increased the affinity of katanin for microtubules and stimulated its ATPase activity. After hydrolysis of ATP, microtubule-bound katanin oligomers disassembled microtubules and then dissociated into free katanin monomers. Coupling a nucleotide-dependent oligomerization cycle to the disassembly of a target protein complex may be a general feature of ATP-hydrolyzing AAA domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hartman, J J -- Vale, R D -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):782-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10531065" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*chemistry/*metabolism ; Adenosine Triphosphate/analogs & derivatives/*metabolism ; Amino Acid Sequence ; Centrifugation, Density Gradient ; Fluorescence ; Hydrolysis ; Luminescent Proteins ; Microtubules/*metabolism ; Models, Biological ; Molecular Sequence Data ; Polymers ; Recombinant Fusion Proteins/chemistry/metabolism ; Tubulin/metabolism
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  • 47
    Publication Date: 1999-06-12
    Description: To monitor changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP). This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons. In dendrites visualized with two-photon laser scanning microscopy or electron microscopy, most of the GluR1-GFP was intracellular, mimicking endogenous GluR1 distribution. Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites. These postsynaptic trafficking events required synaptic N-methyl-D-aspartate (NMDA) receptor activation and may contribute to the enhanced AMPA receptor-mediatedtransmission observed during long-term potentiation and activity-dependent synaptic maturation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, S H -- Hayashi, Y -- Petralia, R S -- Zaman, S H -- Wenthold, R J -- Svoboda, K -- Malinow, R -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1811-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364548" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dendrites/*metabolism/ultrastructure ; Electric Stimulation ; Hippocampus/cytology/physiology ; Humans ; Long-Term Potentiation ; *Neuronal Plasticity ; Neurons/*physiology ; Organ Culture Techniques ; Rats ; Receptor Aggregation ; Receptors, AMPA/*metabolism ; Receptors, N-Methyl-D-Aspartate/*physiology ; Recombinant Fusion Proteins/metabolism ; Synapses/metabolism/*physiology ; Synaptic Transmission ; Tetany
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  • 48
    Publication Date: 1999-01-23
    Description: The plant hormone abscisic acid (ABA) regulates potassium and chloride ion channels at the plasma membrane of guard cells, leading to stomatal closure that reduces transpirational water loss from the leaf. The tobacco Nt-SYR1 gene encodes a syntaxin that is associated with the plasma membrane. Syntaxins and related SNARE proteins aid intracellular vesicle trafficking, fusion, and secretion. Disrupting Nt-Syr1 function by cleavage with Clostridium botulinum type C toxin or competition with a soluble fragment of Nt-Syr1 prevents potassium and chloride ion channel response to ABA in guard cells and implicates Nt-Syr1 in an ABA-signaling cascade.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leyman, B -- Geelen, D -- Quintero, F J -- Blatt, M R -- New York, N.Y. -- Science. 1999 Jan 22;283(5401):537-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Plant Physiology and Biophysics, University of London, Wye College, Wye, Kent TN25 5AH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9915701" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid/*pharmacology ; Amino Acid Sequence ; Animals ; Botulinum Toxins/metabolism ; Cell Membrane/physiology ; Chloride Channels/*physiology ; Genes, Plant ; Genetic Complementation Test ; Ion Channel Gating/drug effects ; Membrane Proteins/chemistry/genetics/*physiology ; Molecular Sequence Data ; Oocytes ; Patch-Clamp Techniques ; Plant Growth Regulators/*pharmacology ; Plant Leaves/*physiology ; *Plants, Toxic ; Potassium Channels/*physiology ; Qa-SNARE Proteins ; Saccharomyces cerevisiae/genetics/growth & development ; Signal Transduction ; Tobacco/genetics/*physiology ; Xenopus
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  • 49
    Publication Date: 1999-11-05
    Description: Glutamatergic neurotransmission is controlled by presynaptic metabotropic glutamate receptors (mGluRs). A subdomain in the intracellular carboxyl-terminal tail of group III mGluRs binds calmodulin and heterotrimeric guanosine triphosphate-binding protein (G protein) betagamma subunits in a mutually exclusive manner. Mutations interfering with calmodulin binding and calmodulin antagonists inhibit G protein-mediated modulation of ionic currents by mGluR 7. Calmodulin antagonists also prevent inhibition of excitatory neurotransmission via presynaptic mGluRs. These results reveal a novel mechanism of presynaptic modulation in which Ca(2+)-calmodulin is required to release G protein betagamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, V -- El Far, O -- Bofill-Cardona, E -- Nanoff, C -- Freissmuth, M -- Karschin, A -- Airas, J M -- Betz, H -- Boehm, S -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1180-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurochemistry, Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10550060" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/metabolism ; Calmodulin/antagonists & inhibitors/*metabolism ; Cells, Cultured ; Dimerization ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; GTP-Binding Proteins/*metabolism ; Glutamic Acid/*metabolism ; Hippocampus/cytology/metabolism ; Humans ; Mice ; Molecular Sequence Data ; Neurons/metabolism ; Potassium Channels/metabolism ; *Potassium Channels, Inwardly Rectifying ; Presynaptic Terminals/metabolism ; Propionates/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate/antagonists & inhibitors/*metabolism ; Recombinant Fusion Proteins/metabolism ; Sesterterpenes ; Signal Transduction ; Swine ; *Synaptic Transmission ; Terpenes/pharmacology
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  • 50
    Publication Date: 1999-02-26
    Description: Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bachmaier, K -- Neu, N -- de la Maza, L M -- Pal, S -- Hessel, A -- Penninger, J M -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1335-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Amgen Institute, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037605" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Amino Acid Sequence ; Animals ; Antigens, Bacterial/chemistry/immunology ; Autoantibodies/biosynthesis ; Autoimmune Diseases/immunology/*microbiology/pathology ; B-Lymphocytes/immunology ; Bacterial Outer Membrane Proteins/chemistry/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Chlamydia/*immunology ; Chlamydia Infections/complications/*immunology ; Chlamydia trachomatis/immunology ; CpG Islands ; Humans ; Immunization ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; *Molecular Mimicry ; Molecular Sequence Data ; Myocarditis/immunology/*microbiology/pathology ; Myocardium/immunology/pathology ; Myosin Heavy Chains/chemistry/*immunology ; Oligodeoxyribonucleotides/immunology ; Sequence Homology, Amino Acid
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  • 51
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-19
    Description: A single kinesin molecule can move "processively" along a microtubule for more than 1 micrometer before detaching from it. The prevailing explanation for this processive movement is the "walking model," which envisions that each of two motor domains (heads) of the kinesin molecule binds coordinately to the microtubule. This implies that each kinesin molecule must have two heads to "walk" and that a single-headed kinesin could not move processively. Here, a motor-domain construct of KIF1A, a single-headed kinesin superfamily protein, was shown to move processively along the microtubule for more than 1 micrometer. The movement along the microtubules was stochastic and fitted a biased Brownian-movement model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Y -- Hirokawa, N -- New York, N.Y. -- Science. 1999 Feb 19;283(5405):1152-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10024239" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Animals ; Catalytic Domain ; Diffusion ; Drosophila ; Kinesin/chemistry/*metabolism ; Kinetics ; Microscopy, Fluorescence ; Microtubules/*metabolism ; Models, Chemical ; Molecular Motor Proteins/chemistry/*metabolism ; Molecular Sequence Data ; Nerve Tissue Proteins/chemistry/*metabolism ; Recombinant Fusion Proteins ; Stochastic Processes ; Thermodynamics
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-24
    Description: Retroviral DNA integration is catalyzed by the viral protein integrase. Here, it is shown that DNA-dependent protein kinase (DNA-PK), a host cell protein, also participates in the reaction. DNA-PK-deficient murine scid cells infected with three different retroviruses showed a substantial reduction in retroviral DNA integration and died by apoptosis. Scid cell killing was not observed after infection with an integrase-defective virus, suggesting that abortive integration is the trigger for death in these DNA repair-deficient cells. These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daniel, R -- Katz, R A -- Skalka, A M -- AI40721/AI/NIAID NIH HHS/ -- AI40835/AI/NIAID NIH HHS/ -- CA71515/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Apr 23;284(5414):644-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10213687" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; CHO Cells ; Cell Survival ; Cells, Cultured ; Cricetinae ; DNA Damage ; *DNA Repair ; DNA, Viral/*genetics/metabolism ; DNA-Activated Protein Kinase ; *DNA-Binding Proteins ; Genetic Vectors ; HIV-1/genetics ; Integrases/genetics/metabolism ; Mice ; Mutation ; Protein-Serine-Threonine Kinases/*metabolism ; Retroviridae/*genetics/physiology ; *Virus Integration ; Virus Replication
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-05
    Description: Costimulation of both the CD3 and CD28 receptors is essential for T cell activation. Induction of adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation. Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation. Selectively reducing PDE7 expression with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition was reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression of PKA activity is required for T cell activation, and inhibition of PDE7 could be an approach to treating T cell-dependent disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Yee, C -- Beavo, J A -- DK21723/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 Feb 5;283(5403):848-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Molecular and Cellular Biology Program, Box 357280, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9933169" target="_blank"〉PubMed〈/a〉
    Keywords: 3',5'-Cyclic-AMP Phosphodiesterases/*biosynthesis/genetics/metabolism ; Antibodies ; Antigens, CD28/immunology/*physiology ; Antigens, CD3/immunology/*physiology ; CD4-Positive T-Lymphocytes/enzymology/immunology ; Cells, Cultured ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 7 ; Enzyme Induction ; Humans ; Interleukin-2/biosynthesis ; Isoenzymes/*biosynthesis/genetics/metabolism ; *Lymphocyte Activation ; Oligonucleotides, Antisense/pharmacology ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes/*enzymology/*immunology/metabolism ; Tumor Cells, Cultured
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  • 54
    Publication Date: 1999-07-31
    Description: Many immune receptors are composed of separate ligand-binding and signal-transducing subunits. In natural killer (NK) and T cells, DAP10 was identified as a cell surface adaptor protein in an activating receptor complex with NKG2D, a receptor for the stress-inducible and tumor-associated major histocompatibility complex molecule MICA. Within the DAP10 cytoplasmic domain, an Src homology 2 (SH2) domain-binding site was capable of recruiting the p85 subunit of the phosphatidylinositol 3-kinase (PI 3-kinase), providing for NKG2D-dependent signal transduction. Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, J -- Song, Y -- Bakker, A B -- Bauer, S -- Spies, T -- Lanier, L L -- Phillips, J H -- AI30581/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):730-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10426994" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cell Line ; Cytotoxicity, Immunologic ; Humans ; Killer Cells, Natural/*immunology/metabolism ; Ligands ; *Lymphocyte Activation ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Molecular Sequence Data ; NK Cell Lectin-Like Receptor Subfamily K ; Neoplasms/immunology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Phosphotyrosine/metabolism ; Receptors, Immunologic/chemistry/genetics/*metabolism ; Receptors, Natural Killer Cell ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism ; Tumor Cells, Cultured ; src Homology Domains
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-03-12
    Description: A central question in immunology is the origin of long-lived T cell memory that confers protection against recurrent infection. The differentiation of naive T cell receptor transgenic CD8+ cells into effector cytotoxic T lymphocytes (CTLs) and memory CD8+ cells was studied. Memory CD8+ cells that were generated after strong antigenic stimulation were the progeny of cytotoxic effectors and retained antigen-specific cytolytic activity 10 weeks after adoptive transfer to antigen-free recipient mice. Thus, potential vaccines based on CTL memory will require the differentiation of naive cells into post-effector memory T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Opferman, J T -- Ober, B T -- Ashton-Rickardt, P G -- 5T32 AI07090/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 Mar 12;283(5408):1745-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Committee on Immunology, Department of Pathology, Committee on Developmental Biology, The University of Chicago, Gwen Knapp Center for Lupus and Immunology Research, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10073942" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Apoptosis ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cells, Cultured ; Cytotoxicity, Immunologic ; Dose-Response Relationship, Immunologic ; H-Y Antigen/immunology ; *Immunologic Memory ; Lymphocyte Activation ; Membrane Glycoproteins/metabolism ; Mice ; Mice, Transgenic ; Perforin ; Pore Forming Cytotoxic Proteins ; T-Lymphocyte Subsets/cytology/*immunology ; T-Lymphocytes, Cytotoxic/cytology/*immunology
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  • 56
    Publication Date: 1999-06-12
    Description: Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siegal, F P -- Kadowaki, N -- Shodell, M -- Fitzgerald-Bocarsly, P A -- Shah, K -- Ho, S -- Antonenko, S -- Liu, Y J -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1835-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Saint Vincents Hospital and Medical Center, New York, NY 10011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364556" target="_blank"〉PubMed〈/a〉
    Keywords: CD40 Ligand ; Cell Lineage ; Cell Separation ; Cells, Cultured ; Dendritic Cells/cytology/*immunology/ultrastructure ; Humans ; Interferon Type I/*biosynthesis ; Interferon-alpha/*biosynthesis/genetics ; Interferon-beta/biosynthesis/genetics ; Interleukin-3/pharmacology ; Leukocytes, Mononuclear/immunology ; Membrane Glycoproteins/pharmacology ; Organelles/ultrastructure ; RNA, Messenger/genetics/metabolism ; Simplexvirus/immunology ; Stem Cells/cytology/immunology
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sikorski, R -- Peters, R -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1868.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10515792" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Genetic Techniques ; Protein Binding ; Proteins/*isolation & purification/metabolism ; Recombinant Fusion Proteins/metabolism ; Ribonucleoproteins, Small Nuclear/metabolism ; Saccharomyces cerevisiae ; Sequence Analysis/*methods
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  • 58
    Publication Date: 2000-01-05
    Description: Phytochromes are a family of photoreceptors used by green plants to entrain their development to the light environment. The distribution of these chromoproteins has been expanded beyond photoautotrophs with the discovery of phytochrome-like proteins in the nonphotosynthetic eubacteria Deinococcus radiodurans and Pseudomonas aeruginosa. Like plant phytochromes, the D. radiodurans receptor covalently binds linear tetrapyrroles autocatalytically to generate a photochromic holoprotein. However, the attachment site is distinct, using a histidine to potentially form a Schiff base linkage. Sequence homology and mutational analysis suggest that D. radiodurans bacteriophytochrome functions as a light-regulated histidine kinase, which helps protect the bacterium from visible light.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S J -- Vener, A V -- Vierstra, R D -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2517-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, Cellular and Molecular Biology Program and Department of Horticulture, University of Wisconsin-Madison, 1575 Linden Drive, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617469" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biliverdine/analogs & derivatives/metabolism ; Binding Sites ; Gram-Positive Cocci/genetics/*metabolism ; Histidine/metabolism ; Light ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Photoreceptors, Microbial/chemistry/genetics/*metabolism ; Phytochrome/metabolism ; Protein Kinases/chemistry/genetics/*metabolism ; Pseudomonas aeruginosa/*metabolism ; Signal Transduction
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  • 59
    Publication Date: 1999-04-09
    Description: Mature Arabidopsis seeds are enriched in storage proteins and lipids, but lack starch. In the shrunken seed 1 (sse1) mutant, however, starch is favored over proteins and lipids as the major storage compound. SSE1 has 26 percent identity with Pex16p in Yarrowia lipolytica and complements pex16 mutants defective in the formation of peroxisomes and the transportation of plasma membrane- and cell wall-associated proteins. In Arabidopsis maturing seeds, SSE1 is required for protein and oil body biogenesis, both of which are endoplasmic reticulum-dependent. Starch accumulation in sse1 suggests that starch formation is a default storage deposition pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Y -- Sun, L -- Nguyen, L V -- Rachubinski, R A -- Goodman, H M -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):328-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195899" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics/*metabolism/ultrastructure ; *Arabidopsis Proteins ; *Fungal Proteins ; Gene Expression ; Genetic Complementation Test ; Membrane Proteins/chemistry/genetics ; Microbodies/metabolism/ultrastructure ; Microscopy, Electron ; Molecular Sequence Data ; Mutation ; Organelles/*metabolism/ultrastructure ; Phenotype ; Plant Oils/metabolism ; Plant Proteins/chemistry/genetics/metabolism/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Saccharomycetales/chemistry/genetics/metabolism ; Seeds/*metabolism/ultrastructure ; Starch/metabolism
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  • 60
    Publication Date: 1999-07-10
    Description: In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium-derived factor (PEDF), a protein previously shown to have neurotrophic activity. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, D W -- Volpert, O V -- Gillis, P -- Crawford, S E -- Xu, H -- Benedict, W -- Bouck, N P -- New York, N.Y. -- Science. 1999 Jul 9;285(5425):245-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology-Immunology, Department of Pathology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10398599" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Antibodies/immunology ; Cattle ; Cells, Cultured ; Chemotaxis/drug effects ; Culture Media, Conditioned ; Endothelial Growth Factors/metabolism ; Endothelium, Vascular/cytology/drug effects/physiology ; Eye/blood supply ; *Eye Proteins ; Humans ; Lymphokines/metabolism ; Mice ; Neovascularization, Pathologic/*drug therapy/metabolism/pathology ; Neovascularization, Physiologic/*drug effects ; *Nerve Growth Factors ; Oxygen/physiology ; Proteins/genetics/immunology/*pharmacology/*physiology ; RNA, Messenger/genetics/metabolism ; Rats ; Retina/*metabolism/pathology ; Retinal Neovascularization/*drug therapy ; Retinal Vessels/growth & development ; Serpins/genetics/immunology/*pharmacology/*physiology ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
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  • 61
    Publication Date: 1999-01-05
    Description: CmPP16 from Cucurbita maxima was cloned and the protein was shown to possess properties similar to those of viral movement proteins. CmPP16 messenger RNA (mRNA) is present in phloem tissue, whereas protein appears confined to sieve elements (SE). Microinjection and grafting studies revealed that CmPP16 moves from cell to cell, mediates the transport of sense and antisense RNA, and moves together with its mRNA into the SE of scion tissue. CmPP16 possesses the characteristics that are likely required to mediate RNA delivery into the long-distance translocation stream. Thus, RNA may move within the phloem as a component of a plant information superhighway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xoconostle-Cazares, B -- Xiang, Y -- Ruiz-Medrano, R -- Wang, H L -- Monzer, J -- Yoo, B C -- McFarland, K C -- Franceschi, V R -- Lucas, W J -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):94-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Plant Biology, Division of Biological Sciences, University of California, Davis, CA 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9872750" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Biological Transport ; Cloning, Molecular ; Cucumis sativus ; Cucurbitaceae/genetics/*metabolism ; Microinjections ; Molecular Sequence Data ; Plant Leaves/metabolism ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Roots/metabolism ; Plant Stems/metabolism ; Plant Viral Movement Proteins ; RNA, Antisense/metabolism ; RNA, Messenger/*metabolism ; RNA, Plant/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Viral Proteins/chemistry/metabolism
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  • 62
    Publication Date: 1999-11-13
    Description: The p42 and p44 mitogen-activated protein kinases (MAPKs), also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as in differentiation programs. The specific role of the p44 MAPK isoform in the whole animal was evaluated by generation of p44 MAPK-deficient mice by homologous recombination in embryonic stem cells. The p44 MAPK-/- mice were viable, fertile, and of normal size. Thus, p44 MAPK is apparently dispensable and p42 MAPK (Erk2) may compensate for its loss. However, in p44 MAPK-/- mice, thymocyte maturation beyond the CD4+CD8+ stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high levels of T cell receptor (CD3high). In p44 MAPK-/- thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells. The p44 MAPK apparently has a specific role in thymocyte development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pages, G -- Guerin, S -- Grall, D -- Bonino, F -- Smith, A -- Anjuere, F -- Auberger, P -- Pouyssegur, J -- New York, N.Y. -- Science. 1999 Nov 12;286(5443):1374-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France. gpages@unice.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10558995" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; Antigens, CD/analysis ; Antigens, CD3/immunology ; Cell Differentiation ; Cell Division ; Cells, Cultured ; DNA/biosynthesis ; Enzyme Activation ; Gene Targeting ; Isoenzymes/genetics/metabolism ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/deficiency/genetics/*metabolism ; Phosphorylation ; Polymorphism, Restriction Fragment Length ; Receptors, Antigen, T-Cell, alpha-beta/analysis/physiology ; T-Lymphocyte Subsets/*cytology/enzymology/immunology ; Tetradecanoylphorbol Acetate/pharmacology ; Thymus Gland/*cytology
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  • 63
    Publication Date: 1999-07-03
    Description: Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, D B -- Lu, Y -- Choate, K A -- Velazquez, H -- Al-Sabban, E -- Praga, M -- Casari, G -- Bettinelli, A -- Colussi, G -- Rodriguez-Soriano, J -- McCredie, D -- Milford, D -- Sanjad, S -- Lifton, R P -- F.1/Telethon/Italy -- R01DK51696/DK/NIDDK NIH HHS/ -- TGM06S01/Telethon/Italy -- New York, N.Y. -- Science. 1999 Jul 2;285(5424):103-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10390358" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Calcium/urine ; Chromosomes, Human, Pair 3/genetics ; Claudins ; Cloning, Molecular ; Female ; Genes, Recessive ; Homeostasis ; Humans ; Kidney Diseases/*genetics/metabolism ; Kidney Tubules/chemistry ; Loop of Henle/chemistry/*metabolism ; Magnesium/blood/*metabolism ; Magnesium Deficiency/*genetics/metabolism ; Male ; Membrane Proteins/analysis/chemistry/genetics/*physiology ; Molecular Sequence Data ; Mutation ; Pedigree ; Physical Chromosome Mapping ; Tight Junctions/*metabolism
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  • 64
    Publication Date: 1999-04-09
    Description: IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK) phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delhase, M -- Hayakawa, M -- Chen, Y -- Karin, M -- R01 AI43477/AI/NIAID NIH HHS/ -- R37 ES04151/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):309-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195894" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Cell Line ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; HeLa Cells ; Helix-Loop-Helix Motifs ; Humans ; I-kappa B Kinase ; I-kappa B Proteins ; Interleukin-1/pharmacology ; Leucine Zippers ; *MAP Kinase Kinase Kinase 1 ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Phosphoserine/metabolism ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Transfection ; Tumor Necrosis Factor-alpha/pharmacology
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  • 65
    Publication Date: 1999-04-16
    Description: Mutation of the VHL tumor suppressor is associated with the inherited von Hippel-Lindau (VHL) cancer syndrome and the majority of kidney cancers. VHL binds the ElonginC-ElonginB complex and regulates levels of hypoxia-inducible proteins. The structure of the ternary complex at 2.7 angstrom resolution shows two interfaces, one between VHL and ElonginC and another between ElonginC and ElonginB. Tumorigenic mutations frequently occur in a 35-residue domain of VHL responsible for ElonginC binding. A mutational patch on a separate domain of VHL indicates a second macromolecular binding site. The structure extends the similarities to the SCF (Skp1-Cul1-F-box protein) complex that targets proteins for degradation, supporting the hypothesis that VHL may function in an analogous pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stebbins, C E -- Kaelin, W G Jr -- Pavletich, N P -- New York, N.Y. -- Science. 1999 Apr 16;284(5413):455-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Structural Biology, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10205047" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Cell Cycle Proteins/chemistry/metabolism ; Cloning, Molecular ; Crystallography, X-Ray ; *Genes, Tumor Suppressor ; Humans ; Hydrogen Bonding ; *Ligases ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Neoplasms/genetics ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry/genetics/metabolism ; S-Phase Kinase-Associated Proteins ; Surface Properties ; Transcription Factors/*chemistry/metabolism ; *Tumor Suppressor Proteins ; *Ubiquitin-Protein Ligases ; Von Hippel-Lindau Tumor Suppressor Protein ; von Hippel-Lindau Disease/*genetics
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  • 66
    Publication Date: 1999-04-09
    Description: The oligomeric IkappaB kinase (IKK) is composed of three polypeptides: IKKalpha and IKKbeta, the catalytic subunits, and IKKgamma, a regulatory subunit. IKKalpha and IKKbeta are similar in structure and thought to have similar function-phosphorylation of the IkappaB inhibitors in response to proinflammatory stimuli. Such phosphorylation leads to degradation of IkappaB and activation of nuclear factor kappaB transcription factors. The physiological function of these protein kinases was explored by analysis of IKKalpha-deficient mice. IKKalpha was not required for activation of IKK and degradation of IkappaB by proinflammatory stimuli. Instead, loss of IKKalpha interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hu, Y -- Baud, V -- Delhase, M -- Zhang, P -- Deerinck, T -- Ellisman, M -- Johnson, R -- Karin, M -- R01 AI43477/AI/NIAID NIH HHS/ -- R37 ES04151/ES/NIEHS NIH HHS/ -- RR04050/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):316-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Cancer Center, University of California San Diego, La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195896" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Multiple/enzymology/genetics ; Animals ; Apoptosis ; Body Patterning ; Bone and Bones/abnormalities/embryology ; Cell Differentiation ; Cell Nucleus/metabolism ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; Dimerization ; *Embryonic and Fetal Development ; Enzyme Activation ; Epidermis/cytology/embryology ; Female ; Gene Targeting ; I-kappa B Kinase ; I-kappa B Proteins ; Keratinocytes ; Limb Deformities, Congenital/enzymology ; Male ; Mice ; *Morphogenesis ; Mutation ; Phosphorylation ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Skin/embryology ; Skin Abnormalities/enzymology
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-09
    Description: Neuronal death induced by activating N-methyl-D-aspartate (NMDA) receptors has been linked to Ca2+ and Na+ influx through associated channels. Whole-cell recording from cultured mouse cortical neurons revealed a NMDA-evoked outward current, INMDA-K, carried by K+ efflux at membrane potentials positive to -86 millivolts. Cortical neurons exposed to NMDA in medium containing reduced Na+ and Ca2+ (as found in ischemic brain tissue) lost substantial intracellular K+ and underwent apoptosis. Both K+ loss and apoptosis were attenuated by increasing extracellular K+, even when voltage-gated Ca2+ channels were blocked. Thus NMDA receptor-mediated K+ efflux may contribute to neuronal apoptosis after brain ischemia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, S P -- Yeh, C -- Strasser, U -- Tian, M -- Choi, D W -- NS 30337/NS/NINDS NIH HHS/ -- NS 32636/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):336-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Calcium/metabolism/pharmacology ; Calcium Channels/metabolism ; Cells, Cultured ; Cerebral Cortex/*cytology/metabolism ; Culture Techniques ; Glutamic Acid/metabolism ; Ion Channel Gating ; Ion Transport ; Membrane Potentials ; Mice ; N-Methylaspartate/pharmacology ; Neocortex/cytology/embryology/metabolism ; Neurons/*cytology/metabolism ; Patch-Clamp Techniques ; Potassium/*metabolism ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Sodium/metabolism/pharmacology
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  • 68
    Publication Date: 1999-10-09
    Description: Norwalk virus, a noncultivatable human calicivirus, is the major cause of epidemic gastroenteritis in humans. The first x-ray structure of a calicivirus capsid, which consists of 180 copies of a single protein, has been determined by phase extension from a low-resolution electron microscopy structure. The capsid protein has a protruding (P) domain connected by a flexible hinge to a shell (S) domain that has a classical eight-stranded beta-sandwich motif. The structure of the P domain is unlike that of any other viral protein with a subdomain exhibiting a fold similar to that of the second domain in the eukaryotic translation elongation factor-Tu. This subdomain, located at the exterior of the capsid, has the largest sequence variation among Norwalk-like human caliciviruses and is likely to contain the determinants of strain specificity and cell binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prasad, B V -- Hardy, M E -- Dokland, T -- Bella, J -- Rossmann, M G -- Estes, M K -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):287-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Verna and Marrs Mclean Department of Biochemistry, Division of Molecular Virology, Baylor College of Medicine, Houston, TX 77030, USA. bprasad@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514371" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Capsid/*chemistry/metabolism ; *Capsid Proteins ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Dimerization ; Genome, Viral ; Humans ; Hydrogen Bonding ; Image Processing, Computer-Assisted ; Models, Molecular ; Molecular Sequence Data ; Norwalk virus/*chemistry/genetics/physiology ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Virus Assembly
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  • 69
    Publication Date: 1999-05-13
    Description: Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diefenbach, A -- Schindler, H -- Rollinghoff, M -- Yokoyama, W M -- Bogdan, C -- New York, N.Y. -- Science. 1999 May 7;284(5416):951-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Klinische Mikrobiologie, Immunologie und Hygiene, Universitat Erlangen, Wasserturmstrasse 3, D-91054 Erlangen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320373" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cyclic GMP/metabolism ; Cytotoxicity, Immunologic ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Immunity, Innate ; Interferon-gamma/biosynthesis/genetics ; Interferons/pharmacology ; Interleukin-12/pharmacology/*physiology ; Janus Kinase 2 ; Killer Cells, Natural/*immunology/metabolism ; *Leishmania major ; Leishmaniasis, Cutaneous/*immunology/metabolism ; Lysine/analogs & derivatives/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/*metabolism ; Nitric Oxide Synthase Type II ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; Proteins/metabolism ; *Proto-Oncogene Proteins ; STAT4 Transcription Factor ; *Signal Transduction ; TYK2 Kinase ; Trans-Activators/metabolism ; Up-Regulation
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  • 70
    Publication Date: 1999-10-09
    Description: Ubiquitination of receptor protein-tyrosine kinases (RPTKs) terminates signaling by marking active receptors for degradation. c-Cbl, an adapter protein for RPTKs, positively regulates RPTK ubiquitination in a manner dependent on its variant SRC homology 2 (SH2) and RING finger domains. Ubiquitin-protein ligases (or E3s) are the components of ubiquitination pathways that recognize target substrates and promote their ligation to ubiquitin. The c-Cbl protein acted as an E3 that can recognize tyrosine-phosphorylated substrates, such as the activated platelet-derived growth factor receptor, through its SH2 domain and that recruits and allosterically activates an E2 ubiquitin-conjugating enzyme through its RING domain. These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joazeiro, C A -- Wing, S S -- Huang, H -- Leverson, J D -- Hunter, T -- Liu, Y C -- CA39780/CA/NCI NIH HHS/ -- R01 DK56558/DK/NIDDK NIH HHS/ -- T32CA09523/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):309-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute, Molecular Biology and Virology Laboratory, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514377" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cell Line ; Humans ; Ligases/chemistry/*metabolism ; Molecular Sequence Data ; Phosphotyrosine/metabolism ; Point Mutation ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-cbl ; Receptor Protein-Tyrosine Kinases/*metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Alignment ; Signal Transduction ; *Ubiquitin-Conjugating Enzymes ; Ubiquitin-Protein Ligases ; Ubiquitins/*metabolism ; src Homology Domains
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  • 71
    Publication Date: 1999-11-13
    Description: A mechanism by which the Ras-mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor-dependent cell survival was characterized. The MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The Rsk-induced phosphorylation of BAD at serine 112 suppressed BAD-mediated apoptosis in neurons. Rsks also are known to phosphorylate the transcription factor CREB (cAMP response element-binding protein) at serine 133. Activated CREB promoted cell survival, and inhibition of CREB phosphorylation at serine 133 triggered apoptosis. These findings suggest that the MAPK signaling pathway promotes cell survival by a dual mechanism comprising the posttranslational modification and inactivation of a component of the cell death machinery and the increased transcription of pro-survival genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bonni, A -- Brunet, A -- West, A E -- Datta, S R -- Takasu, M A -- Greenberg, M E -- NIHP30-HD18655/HD/NICHD NIH HHS/ -- P01 HD 24926/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1999 Nov 12;286(5443):1358-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Neuroscience, Children's Hospital, and Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10558990" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Brain-Derived Neurotrophic Factor/pharmacology ; Carrier Proteins/genetics/metabolism ; *Cell Survival ; Cells, Cultured ; Cerebellum/cytology ; Cyclic AMP Response Element-Binding Protein/metabolism ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Flavonoids/pharmacology ; Insulin-Like Growth Factor I/pharmacology ; MAP Kinase Kinase 1 ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; Mutation ; Neurons/*cytology/metabolism ; Phosphorylation ; Phosphoserine/metabolism ; *Protein-Serine-Threonine Kinases ; Rats ; Rats, Long-Evans ; Recombinant Fusion Proteins/metabolism ; Ribosomal Protein S6 Kinases/genetics/*metabolism ; *Transcription, Genetic ; Transfection ; bcl-Associated Death Protein ; ras Proteins/metabolism
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-18
    Description: Neurotrophins have been implicated in activity-dependent synaptic plasticity, but the underlying intracellular mechanisms remain largely unknown. Synaptic potentiation induced by brain-derived neurotrophic factor (BDNF), but not neurotrophin 3, was prevented by blockers of adenosine 3',5'-monophosphate (cAMP) signaling. Activators of cAMP signaling alone were ineffective in modifying synaptic efficacy but greatly enhanced the potentiation effect of BDNF. Blocking cAMP signaling abolished the facilitation of BDNF-induced potentiation by presynaptic activity. Thus synaptic actions of BDNF are gated by cAMP. Activity and other coincident signals that modulate cAMP concentrations may specify the action of secreted neurotrophins on developing nerve terminals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boulanger, L -- Poo, M M -- NS 37831/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Jun 18;284(5422):1982-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California at San Diego, La Jolla, CA 92093-0357, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10373115" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain-Derived Neurotrophic Factor/*pharmacology ; *Carbazoles ; Cells, Cultured ; Cyclic AMP/analogs & derivatives/pharmacology/*physiology ; Cycloleucine/analogs & derivatives/pharmacology ; *Excitatory Postsynaptic Potentials/drug effects ; Indoles/pharmacology ; Nerve Growth Factors/pharmacology ; Neuronal Plasticity ; Neurons/cytology/physiology ; Neurotrophin 3 ; Okadaic Acid/pharmacology ; Patch-Clamp Techniques ; Pyrroles/pharmacology ; Signal Transduction ; Synapses/drug effects/*physiology ; *Synaptic Transmission/drug effects ; Thionucleotides/pharmacology ; Xenopus
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ferber, D -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1651, 1653.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523177" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*adverse effects ; Apoptosis/*drug effects ; Benzothiazoles ; Cell Division/drug effects/radiation effects ; Cells, Cultured ; Drug Evaluation, Preclinical ; Gamma Rays/*adverse effects ; Humans ; Mice ; Neoplasms/drug therapy/radiotherapy/*therapy ; Radiation Dosage ; Radiation Tolerance/*drug effects ; Thiazoles/*pharmacology ; Toluene/*analogs & derivatives/pharmacology ; Tumor Suppressor Protein p53/*antagonists & inhibitors/physiology
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  • 74
    Publication Date: 1999-03-19
    Description: In higher plants, organogenesis occurs continuously from self-renewing apical meristems. Arabidopsis thaliana plants with loss-of-function mutations in the CLAVATA (CLV1, 2, and 3) genes have enlarged meristems and generate extra floral organs. Genetic analysis indicates that CLV1, which encodes a receptor kinase, acts with CLV3 to control the balance between meristem cell proliferation and differentiation. CLV3 encodes a small, predicted extracellular protein. CLV3 acts nonautonomously in meristems and is expressed at the meristem surface overlying the CLV1 domain. These proteins may act as a ligand-receptor pair in a signal transduction pathway, coordinating growth between adjacent meristematic regions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fletcher, J C -- Brand, U -- Running, M P -- Simon, R -- Meyerowitz, E M -- New York, N.Y. -- Science. 1999 Mar 19;283(5409):1911-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10082464" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/*cytology/genetics/growth & development/metabolism ; *Arabidopsis Proteins ; Cell Differentiation ; Cell Division ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genes, Plant ; In Situ Hybridization ; Ligands ; Meristem/*cytology/growth & development/metabolism ; Molecular Sequence Data ; Mutation ; Phenotype ; Plant Proteins/chemistry/genetics/*metabolism ; Plant Shoots/cytology ; RNA, Messenger/genetics/metabolism ; RNA, Plant/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction
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  • 75
    Publication Date: 1999-07-10
    Description: Drug resistance of pathogens is an increasing problem whose underlying mechanisms are not fully understood. Cellular uptake of the major drugs against Trypanosoma brucei spp., the causative agents of sleeping sickness, is thought to occur through an unusual, so far unidentified adenosine transporter. Saccharomyces cerevisiae was used in a functional screen to clone a gene (TbAT1) from Trypanosoma brucei brucei that encodes a nucleoside transporter. When expressed in yeast, TbAT1 enabled adenosine uptake and conferred susceptibility to melaminophenyl arsenicals. Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maser, P -- Sutterlin, C -- Kralli, A -- Kaminsky, R -- New York, N.Y. -- Science. 1999 Jul 9;285(5425):242-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Tropical Institute, CH-4002 Basel, Switzerland. Biozentrum, University of Basel, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10398598" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*metabolism ; Amino Acid Sequence ; Animals ; Arsenicals/metabolism/pharmacology ; Biological Transport ; Carrier Proteins/chemistry/genetics/*metabolism ; Cloning, Molecular ; Drug Resistance/genetics ; Genes, Protozoan ; Membrane Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Nucleoside Transport Proteins ; Nucleosides/metabolism ; Purines/metabolism/pharmacology ; Saccharomyces cerevisiae/genetics ; Substrate Specificity ; Trypanocidal Agents/metabolism/*pharmacology ; Trypanosoma brucei brucei/*drug effects/genetics/*metabolism ; Trypanosomiasis, African/drug therapy/parasitology
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-03-19
    Description: The role of localized instability of the actin network in specifying axonal fate was examined with the use of rat hippocampal neurons in culture. During normal neuronal development, actin dynamics and instability polarized to a single growth cone before axon formation. Consistently, global application of actin-depolymerizing drugs and of the Rho-signaling inactivator toxin B to nonpolarized cells produced neurons with multiple axons. Moreover, disruption of the actin network in one individual growth cone induced its neurite to become the axon. Thus, local instability of the actin network restricted to a single growth cone is a physiological signal specifying neuronal polarization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bradke, F -- Dotti, C G -- New York, N.Y. -- Science. 1999 Mar 19;283(5409):1931-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Cell Biology Programme, Meyerhofstrasse 1, 69012 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10082468" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism/*physiology ; Animals ; Axons/*physiology/ultrastructure ; *Bacterial Proteins ; Bacterial Toxins/pharmacology ; Bicyclo Compounds, Heterocyclic/pharmacology ; Cell Polarity ; Cells, Cultured ; Cytochalasin D/pharmacology ; GTP Phosphohydrolases/antagonists & inhibitors/metabolism ; Growth Cones/drug effects/*physiology/ultrastructure ; Hippocampus ; Microtubules/physiology/ultrastructure ; Neurites/*physiology/ultrastructure ; Phenotype ; Pseudopodia/drug effects/ultrastructure ; Rats ; Signal Transduction ; Thiazoles/pharmacology ; Thiazolidines
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  • 77
    Publication Date: 1999-04-02
    Description: The ability of p53 to promote apoptosis in response to mitogenic oncogenes appears to be critical for its tumor suppressor function. Caspase-9 and its cofactor Apaf-1 were found to be essential downstream components of p53 in Myc-induced apoptosis. Like p53 null cells, mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors. Inactivation of Apaf-1 or caspase-9 substituted for p53 loss in promoting the oncogenic transformation of Myc-expressing cells. These results imply a role for Apaf-1 and caspase-9 in controlling tumor development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soengas, M S -- Alarcon, R M -- Yoshida, H -- Giaccia, A J -- Hakem, R -- Mak, T W -- Lowe, S W -- CA13106/CA/NCI NIH HHS/ -- CA64489/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 2;284(5411):156-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10102818" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptotic Protease-Activating Factor 1 ; Caspase 9 ; Caspases/genetics/*physiology ; Cell Division ; Cell Transformation, Neoplastic ; Cells, Cultured ; Cytochrome c Group/metabolism ; Genes, myc ; *Genes, p53 ; Genes, ras ; Mice ; Mice, Nude ; Mitochondria/metabolism ; Mutation ; Neoplasms, Experimental/genetics/metabolism/*pathology ; Proteins/genetics/*physiology ; Tumor Suppressor Protein p53/metabolism
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solter, D -- Gearhart, J -- New York, N.Y. -- Science. 1999 Mar 5;283(5407):1468-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Max Planck Institute of Immunology, Freiburg, Germany. solter@immunbio.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10206877" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bioethics ; Blastocyst/*cytology ; *Cell Differentiation ; Cell Line ; Cells, Cultured ; Cloning, Organism ; Cytoplasm/physiology ; Embryo, Mammalian/cytology ; Humans ; Mice ; Nuclear Transfer Techniques ; Stem Cells/*cytology
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  • 79
    Publication Date: 1999-10-16
    Description: Analysis of rhesus macaque leukocytes disclosed the presence of an 18-residue macrocyclic, tridisulfide antibiotic peptide in granules of neutrophils and monocytes. The peptide, termed rhesus theta defensin-1 (RTD-1), is microbicidal for bacteria and fungi at low micromolar concentrations. Antibacterial activity of the cyclic peptide was threefold greater than that of an open-chain analog, and the cyclic conformation was required for antimicrobial activity in the presence of 150 millimolar sodium chloride. Biosynthesis of RTD-1 involves the head-to-tail ligation of two alpha-defensin-related nonapeptides, requiring the formation of two new peptide bonds. Thus, host defense cells possess mechanisms for synthesis and granular packaging of macrocyclic antibiotic peptides that are components of the phagocyte antimicrobial armamentarium.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tang, Y Q -- Yuan, J -- Osapay, G -- Osapay, K -- Tran, D -- Miller, C J -- Ouellette, A J -- Selsted, M E -- AI22931/AI/NIAID NIH HHS/ -- DK33506/DK/NIDDK NIH HHS/ -- DK44632/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):498-502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, College of Medicine, University of California, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10521339" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Bacterial Agents ; Anti-Infective Agents/chemistry/*metabolism/pharmacology ; Bacteria/drug effects ; Cloning, Molecular ; Defensins ; Disulfides/chemistry ; Fungi/drug effects ; Humans ; Leukopoiesis ; Macaca mulatta ; Molecular Sequence Data ; Monocytes/*metabolism ; Neutrophils/*metabolism ; Oligopeptides/chemistry/genetics/metabolism ; Osmolar Concentration ; Peptides, Cyclic/*biosynthesis/chemistry/genetics/pharmacology ; *Protein Biosynthesis ; Protein Conformation ; Protein Precursors/chemistry/genetics/metabolism ; Protein Processing, Post-Translational ; Proteins/chemistry/genetics/pharmacology
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1247, 1249.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10084927" target="_blank"〉PubMed〈/a〉
    Keywords: 14-3-3 Proteins ; Amino Acid Sequence ; Cell Cycle Proteins/metabolism ; Cell Nucleus/metabolism ; *Conserved Sequence ; Mitosis ; Peptidylprolyl Isomerase/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphoproteins/chemistry/*metabolism ; Phosphorylation ; Phosphoserine/*metabolism ; Phosphotyrosine/metabolism ; Protein Binding ; Proteins/*chemistry/*metabolism ; *Tyrosine 3-Monooxygenase ; cdc25 Phosphatases
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 81
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-05
    Description: Whether a single major histocompatibility complex (MHC)-bound peptide can drive the positive selection of large numbers of T cells has been a controversial issue. A diverse population of self peptides was shown to be essential for the in vivo development of CD4 T cells. Mice in which all but 5 percent of MHC class II molecules were bound by a single peptide had wild-type numbers of CD4 T cells. However, when the diversity within this 5 percent was lost, CD4 T cell development was impaired. Blocking the major peptide-MHC complex in thymus organ culture had no effect on T cell development, indicating that positive selection occurred on the diverse peptides present at low levels. This requirement for peptide diversity indicates that the interaction between self peptides and T cell receptors during positive selection is highly specific.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barton, G M -- Rudensky, A Y -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):67-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cellular Biology Program of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9872742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; CD4-Positive T-Lymphocytes/cytology/*immunology/metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cells, Cultured ; Histocompatibility Antigens Class II/*immunology/metabolism ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Knockout ; Mice, Transgenic ; Peptides/*immunology/metabolism ; Receptors, Antigen, T-Cell/*immunology ; Recombinant Fusion Proteins/metabolism ; Spleen/immunology ; Thymus Gland/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 82
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-06
    Description: A human cytomegalovirus gene array was used to identify a previously unidentified class of viral transcripts. These transcripts, termed virion RNAs, were packaged within infectious virions and were delivered to the host cell on infection. This mechanism of herpesvirus gene expression allows for viral genes to be expressed within an infected cell immediately after virus entry and in the absence of transcription from the viral genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bresnahan, W A -- Shenk, T -- CA85786/CA/NCI NIH HHS/ -- F32 AI010448/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2373-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875924" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Nucleus/metabolism ; Cells, Cultured ; Cytomegalovirus/*genetics/*physiology ; Dactinomycin/pharmacology ; Gene Expression ; Genes, Viral ; Genome, Viral ; Golgi Apparatus/metabolism ; Humans ; Nucleic Acid Hybridization ; Nucleic Acid Synthesis Inhibitors/pharmacology ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger/*genetics/isolation & purification/metabolism ; RNA, Viral/*genetics/isolation & purification/metabolism ; Recombinant Fusion Proteins/metabolism ; Transcription, Genetic ; Viral Proteins/genetics/metabolism ; Virion/*genetics/physiology ; Virus Assembly
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  • 83
    Publication Date: 2000-09-01
    Description: Activation of the transcription factor nuclear factor (NF)-kappaB by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappaB requires the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino-terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉May, M J -- D'Acquisto, F -- Madge, L A -- Glockner, J -- Pober, J S -- Ghosh, S -- AI 33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1550-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968790" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology ; COS Cells ; Cells, Cultured ; E-Selectin/biosynthesis/genetics ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; I-kappa B Kinase ; Inflammation/drug therapy ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; NF-kappa B/*metabolism ; Peptides/chemistry/*pharmacology ; Point Mutation ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism
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  • 84
    Publication Date: 2000-03-04
    Description: The large chlorella virus PBCV-1, which contains double-stranded DNA (dsDNA), encodes a 94-codon open reading frame (ORF) that contains a motif resembling the signature sequence of the pore domain of potassium channel proteins. Phylogenetic analyses of the encoded protein, Kcv, indicate a previously unidentified type of potassium channel. The messenger RNA encoded by the ORF leads to functional expression of a potassium-selective conductance in Xenopus laevis oocytes. The channel blockers amantadine and barium, but not cesium, inhibit this conductance, in addition to virus plaque formation. Thus, PBCV-1 encodes the first known viral protein that functions as a potassium-selective channel and is essential in the virus life cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plugge, B -- Gazzarrini, S -- Nelson, M -- Cerana, R -- Van Etten, J L -- Derst, C -- DiFrancesco, D -- Moroni, A -- Thiel, G -- 971/Telethon/Italy -- GM32441/GM/NIGMS NIH HHS/ -- GM41333/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 3;287(5458):1641-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Albrecht-von-Haller-Institut fur Pflanzenwissenschaften, Universitat Gottingen, 37073 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10698737" target="_blank"〉PubMed〈/a〉
    Keywords: Amantadine/pharmacology ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Barium/pharmacology ; Cesium/pharmacology ; Chlorella/virology ; Isoelectric Point ; Molecular Sequence Data ; Molecular Weight ; Oocytes ; Patch-Clamp Techniques ; Phycodnaviridae/chemistry/drug effects/*genetics/*physiology ; Potassium/metabolism ; Potassium Channels/*chemistry/genetics/*physiology ; RNA, Messenger/genetics/metabolism ; Recombinant Proteins/metabolism ; Sodium/metabolism ; Viral Plaque Assay ; *Viral Proteins ; Virus Replication/drug effects ; Xenopus laevis
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  • 85
    Publication Date: 1999-12-30
    Description: The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an alpha helix, and a beta strand, interacts with the beta sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas interactions between the SARA beta strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, G -- Chen, Y G -- Ozdamar, B -- Gyuricza, C A -- Chong, P A -- Wrana, J L -- Massague, J -- Shi, Y -- CA85171/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 7;287(5450):92-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10615055" target="_blank"〉PubMed〈/a〉
    Keywords: *Activin Receptors, Type I ; Amino Acid Sequence ; Binding Sites ; Carrier Proteins/*chemistry/*metabolism ; Crystallography, X-Ray ; DNA-Binding Proteins/*chemistry/genetics/*metabolism ; Hydrogen Bonding ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Phosphorylation ; Point Mutation ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/metabolism ; Receptors, Transforming Growth Factor beta/chemistry/genetics/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Signal Transduction ; Smad2 Protein ; Trans-Activators/*chemistry/genetics/*metabolism ; Zinc Fingers
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  • 86
    Publication Date: 2000-05-29
    Description: Pathogenic mycobacteria, including the agent of tuberculosis, Mycobacterium tuberculosis, must replicate in macrophages for long-term persistence within their niche during chronic infection: organized collections of macrophages and lymphocytes called granulomas. We identified several genes preferentially expressed when Mycobacterium marinum, the cause of fish and amphibian tuberculosis, resides in host granulomas and/or macrophages. Two were homologs of M. tuberculosis PE/PE-PGRS genes, a family encoding numerous repetitive glycine-rich proteins of unknown function. Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophages and with decreased persistence in granulomas. Our results establish a direct role in virulence for some PE-PGRS proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramakrishnan, L -- Federspiel, N A -- Falkow, S -- AI 32396/AI/NIAID NIH HHS/ -- K08 AI 01400/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 May 26;288(5470):1436-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. lalitar@cmgm.stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10827956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/chemistry/*genetics ; Cells, Cultured ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Glycine/analysis ; Granuloma/*microbiology/pathology ; Humans ; Macrophages/*microbiology ; Mutation ; Mycobacterium Infections, Nontuberculous/*microbiology/pathology ; Mycobacterium marinum/*genetics/growth & development/*pathogenicity ; Mycobacterium tuberculosis/genetics/pathogenicity ; Promoter Regions, Genetic ; Rana pipiens ; Tuberculosis/microbiology ; Virulence
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  • 87
    Publication Date: 2000-10-20
    Description: Ectodysplasin, a member of the tumor necrosis factor family, is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Mutations in EDA give rise to a clinical syndrome characterized by loss of hair, sweat glands, and teeth. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by an insertion of two amino acids. This insertion functions to determine receptor binding specificity, such that EDA-A1 binds only the receptor EDAR, whereas EDA-A2 binds only the related, but distinct, X-linked ectodysplasin-A2 receptor (XEDAR). In situ binding and organ culture studies indicate that EDA-A1 and EDA-A2 are differentially expressed and play a role in epidermal morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, M -- Wang, L C -- Hymowitz, S G -- Schilbach, S -- Lee, J -- Goddard, A -- de Vos, A M -- Gao, W Q -- Dixit, V M -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):523-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Oncology, Genentech, 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/11039935" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Binding Sites ; Cell Line ; DNA-Binding Proteins/metabolism ; Ectodermal Dysplasia/genetics ; Ectodysplasins ; Epidermis/embryology/*metabolism ; Humans ; *I-kappa B Proteins ; In Situ Hybridization ; Ligands ; Membrane Proteins/*chemistry/*metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Morphogenesis ; NF-kappa B/metabolism ; Phosphorylation ; Point Mutation ; Protein Conformation ; Proteins/metabolism ; Receptors, Cell Surface/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; TNF Receptor-Associated Factor 6 ; Transfection
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  • 88
    Publication Date: 2000-07-15
    Description: Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Coviella, I -- Berse, B -- Krauss, R -- Thies, R S -- Blusztajn, J K -- P01 AG09525/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):313-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894782" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/biosynthesis ; Animals ; Bone Morphogenetic Proteins/*physiology ; Carrier Proteins/genetics ; Cells, Cultured ; Central Nervous System ; Choline O-Acetyltransferase/genetics ; Embryo, Mammalian/metabolism ; Fibroblast Growth Factor 2/physiology ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Growth Differentiation Factor 2 ; *Membrane Transport Proteins ; Mice ; Neurons/metabolism ; Phenotype ; RNA, Messenger/metabolism ; Septum of Brain/embryology/metabolism ; Spinal Cord/embryology/metabolism ; Up-Regulation ; Vesicular Acetylcholine Transport Proteins ; *Vesicular Transport Proteins
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  • 89
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-10
    Description: A Drosophila model for Huntington's and other polyglutamine diseases was used to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye. Among 7000 P-element insertions, several suppressor strains were isolated, two of which led to the discovery of the suppressor genes described here. The predicted product of one, dHDJ1, is homologous to human heat shock protein 40/HDJ1. That of the second, dTPR2, is homologous to the human tetratricopeptide repeat protein 2. Each of these molecules contains a chaperone-related J domain. Their suppression of polyglutamine toxicity was verified in transgenic flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazemi-Esfarjani, P -- Benzer, S -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1837-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. parsa@its.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Cloning, Molecular ; Crosses, Genetic ; DNA Transposable Elements ; Disease Models, Animal ; *Drosophila Proteins ; Drosophila melanogaster/anatomy & histology/embryology/*genetics/metabolism ; Expressed Sequence Tags ; Eye/metabolism ; Eye Abnormalities ; Female ; Genes, Insect ; *Genes, Suppressor ; HSP40 Heat-Shock Proteins ; Heat-Shock Proteins/chemistry/*genetics/physiology ; Male ; Molecular Sequence Data ; *Nerve Degeneration ; Neurodegenerative Diseases ; Peptides/genetics/*metabolism ; Phenotype ; Proteins/chemistry ; Repetitive Sequences, Nucleic Acid ; Retina/metabolism ; Suppression, Genetic
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  • 90
    Publication Date: 2000-02-11
    Description: The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell-mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of HLA-E depends on binding of conserved peptides derived from MHC class I molecules. The same peptide is present in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associated with antigen processing, gpUL40 can up-regulate expression of HLA-E, which protects targets from NK cell lysis. While classical MHC class I molecules are down-regulated, HLA-E is up-regulated by HCMV. Induction of HLA-E surface expression by gpUL40 may represent an escape route for HCMV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomasec, P -- Braud, V M -- Rickards, C -- Powell, M B -- McSharry, B P -- Gadola, S -- Cerundolo, V -- Borysiewicz, L K -- McMichael, A J -- Wilkinson, G W -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1031.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Wales College of Medicine, Cardiff CF14 4XN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669413" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; *Antigens, CD ; Cell Line ; Cell Membrane/immunology ; Cells, Cultured ; Conserved Sequence ; Cytomegalovirus/genetics/immunology/*metabolism ; Cytotoxicity, Immunologic ; Down-Regulation ; HLA Antigens/immunology/*metabolism ; Histocompatibility Antigens Class I/immunology/*metabolism ; Humans ; Killer Cells, Natural/*immunology ; Molecular Sequence Data ; Open Reading Frames ; Protein Sorting Signals/chemistry/*metabolism ; Receptors, Immunologic/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Transfection ; Up-Regulation ; Viral Proteins/chemistry/genetics/*metabolism
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  • 91
    Publication Date: 2000-05-08
    Description: The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tournier, C -- Hess, P -- Yang, D D -- Xu, J -- Turner, T K -- Nimnual, A -- Bar-Sagi, D -- Jones, S N -- Flavell, R A -- Davis, R J -- New York, N.Y. -- Science. 2000 May 5;288(5467):870-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry & Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10797012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptotic Protease-Activating Factor 1 ; Caspase 3 ; Caspase 9 ; Caspases/metabolism ; Cell Count ; Cell Division ; Cells, Cultured ; Cytochrome c Group/*metabolism ; DNA Fragmentation ; Enzyme Activation ; Fibroblasts ; Gene Targeting ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System ; Methyl Methanesulfonate/pharmacology ; Mice ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinases/genetics/*metabolism ; NF-kappa B/metabolism ; *Protein-Serine-Threonine Kinases ; Proteins/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Ultraviolet Rays
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  • 92
    Publication Date: 2000-04-25
    Description: Susceptibility to murine and human insulin-dependent diabetes mellitus correlates strongly with major histocompatibility complex (MHC) class II I-A or HLA-DQ alleles that lack an aspartic acid at position beta57. I-Ag7 lacks this aspartate and is the only class II allele expressed by the nonobese diabetic mouse. The crystal structure of I-Ag7 was determined at 2.6 angstrom resolution as a complex with a high-affinity peptide from the autoantigen glutamic acid decarboxylase (GAD) 65. I-Ag7 has a substantially wider peptide-binding groove around beta57, which accounts for distinct peptide preferences compared with other MHC class II alleles. Loss of Asp(beta57) leads to an oxyanion hole in I-Ag7 that can be filled by peptide carboxyl residues or, perhaps, through interaction with the T cell receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corper, A L -- Stratmann, T -- Apostolopoulos, V -- Scott, C A -- Garcia, K C -- Kang, A S -- Wilson, I A -- Teyton, L -- CA58896/CA/NCI NIH HHS/ -- DK55037/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):505-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Skaggs Institute for Chemical Biology, The 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/10775108" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Aspartic Acid/chemistry ; Crystallography, X-Ray ; Diabetes Mellitus, Type 1/*immunology ; Drosophila melanogaster ; *Genes, MHC Class II ; Glutamate Decarboxylase/metabolism ; Histocompatibility Antigens Class II/*chemistry/genetics/metabolism ; Humans ; Hydrogen Bonding ; Mice ; Mice, Inbred NOD ; Models, Molecular ; Molecular Sequence Data ; Peptide Library ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell/metabolism ; Recombinant Proteins/chemistry/metabolism
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  • 93
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-31
    Description: All cellular organisms use specialized RNA polymerases called "primases" to synthesize RNA primers for the initiation of DNA replication. The high-resolution crystal structure of a primase, comprising the catalytic core of the Escherichia coli DnaG protein, was determined. The core structure contains an active-site architecture that is unrelated to other DNA or RNA polymerase palm folds, but is instead related to the "toprim" fold. On the basis of the structure, it is likely that DnaG binds nucleic acid in a groove clustered with invariant residues and that DnaG is positioned within the replisome to accept single-stranded DNA directly from the replicative helicase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keck, J L -- Roche, D D -- Lynch, A S -- Berger, J M -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2482-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, 229 Stanley Hall, no. 3206, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10741967" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; DNA Helicases/chemistry/metabolism ; DNA Primase/*chemistry/*metabolism ; DNA Replication ; DNA, Bacterial/metabolism ; DNA, Single-Stranded/*metabolism ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Escherichia coli/*enzymology/metabolism ; Metals/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/biosynthesis ; Recombinant Proteins/chemistry/metabolism ; Templates, Genetic
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  • 94
    Publication Date: 2000-08-05
    Description: The circadian oscillator of the cyanobacterium Synechococcus elongatus, like those in eukaryotes, is entrained by environmental cues. Inactivation of the gene cikA (circadian input kinase) shortens the circadian period of gene expression rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The CikA protein sequence reveals that it is a divergent bacteriophytochrome with characteristic histidine protein kinase motifs and a cryptic response regulator motif. CikA is likely a key component of a pathway that provides environmental input to the circadian oscillator in S. elongatus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmitz, O -- Katayama, M -- Williams, S B -- Kondo, T -- Golden, S S -- GM37040/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):765-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10926536" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; *Bacterial Proteins ; *Biological Clocks/genetics/physiology ; *Circadian Rhythm/genetics/physiology ; Cyanobacteria/genetics/*physiology ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Reporter ; Luminescent Measurements ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Kinases/chemistry/*genetics/physiology ; Sequence Alignment
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  • 95
    Publication Date: 2000-04-25
    Description: Major histocompatibility complex class II (MHC II) molecules capture peptides within the endocytic pathway to generate T cell receptor (TCR) ligands. Immature dendritic cells (DCs) sequester intact antigens in lysosomes, processing and converting antigens into peptide-MHC II complexes upon induction of DC maturation. The complexes then accumulate in distinctive, nonlysosomal MHC II+ vesicles that appear to migrate to the cell surface. Although the vesicles exclude soluble lysosomal contents and antigen-processing machinery, many contain MHC I and B7 costimulatory molecules. After arrival at the cell surface, the MHC and costimulatory molecules remain clustered. Thus, transport of peptide-MHC II complexes by DCs not only accomplishes transfer from late endocytic compartments to the plasma membrane, but does so in a manner that selectively concentrates TCR ligands and costimulatory molecules for T cell contact.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turley, S J -- Inaba, K -- Garrett, W S -- Ebersold, M -- Unternaehrer, J -- Steinman, R M -- Mellman, I -- AI-13013/AI/NIAID NIH HHS/ -- AI-34098/AI/NIAID NIH HHS/ -- AI-39672/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):522-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520-8002, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10775112" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; *Antigen Presentation ; Antigens, CD/immunology/metabolism ; Antigens, CD86 ; B-Lymphocytes/immunology/metabolism ; Bicyclo Compounds, Heterocyclic/pharmacology ; Biological Transport ; Cell Membrane/immunology/metabolism ; Cells, Cultured ; Dendritic Cells/*immunology/*metabolism ; Endocytosis ; Endosomes/immunology/metabolism ; Histocompatibility Antigens Class I/immunology/metabolism ; Histocompatibility Antigens Class II/immunology/*metabolism ; Kinetics ; Ligands ; Lipopolysaccharides/immunology ; Lysosomes/immunology/metabolism ; Membrane Glycoproteins/immunology/metabolism ; Mice ; Mice, Inbred C3H ; Muramidase/immunology/*metabolism ; Peptide Fragments/immunology/*metabolism ; Receptors, Antigen, T-Cell/metabolism ; Thiazoles/pharmacology ; Thiazolidines
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2133-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10744529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Chemoreceptor Cells/*physiology ; Humans ; Mice ; Multigene Family ; Receptors, Cell Surface/genetics/*physiology ; *Taste ; Taste Buds/*physiology ; Transducin/biosynthesis
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  • 97
    Publication Date: 2001-02-07
    Description: Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum. Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces between 100 and 200 piconewtons for the different helices were found. Upon extraction, the helices were found to unfold. The force spectra revealed the individuality of the unfolding pathways. Helices G and F as well as helices E and D always unfolded pairwise, whereas helices B and C occasionally unfolded one after the other. Experiments with cleaved loops revealed the origin of the individuality: stabilization of helix B by neighboring helices.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oesterhelt, F -- Oesterhelt, D -- Pfeiffer, M -- Engel, A -- Gaub, H E -- Muller, D J -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):143-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CeNS and Lehrstuhl fur angewandte Physik, Ludwig Maximilians-Universitat Munchen, Amalienstrasse 54, 80799 Munchen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753119" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriorhodopsins/*chemistry/genetics ; Cysteine/chemistry ; Halobacterium salinarum/*chemistry ; Membrane Proteins/*chemistry/genetics ; *Microscopy, Atomic Force ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Protein Denaturation ; *Protein Folding ; Protein Structure, Secondary ; Purple Membrane/*chemistry ; Serine Endopeptidases/metabolism ; Spectrum Analysis
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  • 98
    Publication Date: 2000-08-19
    Description: Pig cloning will have a marked impact on the optimization of meat production and xenotransplantation. To clone pigs from differentiated cells, we microinjected the nuclei of porcine (Sus scrofa) fetal fibroblasts into enucleated oocytes, and development was induced by electroactivation. The transfer of 110 cloned embryos to four surrogate mothers produced an apparently normal female piglet. The clonal provenance of the piglet was indicated by her coat color and confirmed by DNA microsatellite analysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onishi, A -- Iwamoto, M -- Akita, T -- Mikawa, S -- Takeda, K -- Awata, T -- Hanada, H -- Perry, A C -- New York, N.Y. -- Science. 2000 Aug 18;289(5482):1188-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Animal Breeding and Genetics, National Institute of Animal Industry, Tsukuba Norin Danchi, Ibaraki-ken 305-0901, Japan. onishi@niai.affrc.go.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10947985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cloning, Organism/*methods ; Electric Stimulation ; Embryo Transfer ; Embryonic and Fetal Development ; Female ; Fetus/cytology ; Fibroblasts/ultrastructure ; Microinjections ; Microsatellite Repeats ; *Nuclear Transfer Techniques ; Oocytes ; Pregnancy ; *Swine/embryology/genetics
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  • 99
    Publication Date: 2000-02-26
    Description: The signal recognition particle (SRP), a protein-RNA complex conserved in all three kingdoms of life, recognizes and transports specific proteins to cellular membranes for insertion or secretion. We describe here the 1.8 angstrom crystal structure of the universal core of the SRP, revealing protein recognition of a distorted RNA minor groove. Nucleotide analog interference mapping demonstrates the biological importance of observed interactions, and genetic results show that this core is functional in vivo. The structure explains why the conserved residues in the protein and RNA are required for SRP assembly and defines a signal sequence recognition surface composed of both protein and RNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Batey, R T -- Rambo, R P -- Lucast, L -- Rha, B -- Doudna, J A -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1232-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, New Haven, CT 06511, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678824" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/*chemistry/metabolism ; Base Pairing ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Escherichia coli/chemistry/genetics/metabolism ; *Escherichia coli Proteins ; Guanosine Triphosphate/metabolism ; Hydrogen Bonding ; Magnesium/metabolism ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Potassium/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/*chemistry/genetics/metabolism ; Signal Recognition Particle/*chemistry/metabolism ; Transformation, Bacterial ; Water/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-29
    Description: Evidence of simian immunodeficiency virus (SIV) infection has been reported for 26 different species of African nonhuman primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of acquired immunodeficiency syndrome (AIDS) in humans. Together, they have been transmitted to humans on at least seven occasions. The implications of human infection by a diverse set of SIVs and of exposure to a plethora of additional human immunodeficiency virus-related viruses are discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hahn, B H -- Shaw, G M -- De Cock, K M -- Sharp, P M -- N01 AI 35338/AI/NIAID NIH HHS/ -- R01 AI 40951/AI/NIAID NIH HHS/ -- R01 AI 44596/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):607-14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA. bhahn@uab.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10649986" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/epidemiology/*transmission/virology ; Africa, Western/epidemiology ; Amino Acid Sequence ; Animals ; Disease Outbreaks ; Disease Reservoirs ; *HIV-1/genetics ; *HIV-2/genetics ; Haplorhini/*virology ; Humans ; Molecular Sequence Data ; Phylogeny ; Public Health ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/classification/genetics/*physiology ; Species Specificity ; Zoonoses/*transmission
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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