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  • Mice  (1,033)
  • United States  (824)
  • Protein Structure, Secondary  (270)
  • Geochemistry, Geophysics
  • American Association for the Advancement of Science (AAAS)  (2,184)
  • 2015-2019  (461)
  • 1995-1999  (1,723)
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  • 1
    Publication Date: 1998-03-21
    Description: The T cell receptor (TCR) inherently has dual specificity. T cells must recognize self-antigens in the thymus during maturation and then discriminate between foreign pathogens in the periphery. A molecular basis for this cross-reactivity is elucidated by the crystal structure of the alloreactive 2C TCR bound to self peptide-major histocompatibility complex (pMHC) antigen H-2Kb-dEV8 refined against anisotropic 3.0 angstrom resolution x-ray data. The interface between peptide and TCR exhibits extremely poor shape complementarity, and the TCR beta chain complementarity-determining region 3 (CDR3) has minimal interaction with the dEV8 peptide. Large conformational changes in three of the TCR CDR loops are induced upon binding, providing a mechanism of structural plasticity to accommodate a variety of different peptide antigens. Extensive TCR interaction with the pMHC alpha helices suggests a generalized orientation that is mediated by the Valpha domain of the TCR and rationalizes how TCRs can effectively "scan" different peptides bound within a large, low-affinity MHC structural framework for those that provide the slight additional kinetic stabilization required for signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, K C -- Degano, M -- Pease, L R -- Huang, M -- Peterson, P A -- Teyton, L -- Wilson, I A -- AI42266/AI/NIAID NIH HHS/ -- AI42267/AI/NIAID NIH HHS/ -- R01 CA58896/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Feb 20;279(5354):1166-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and the Skaggs Institute of 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/9469799" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallization ; Crystallography, X-Ray ; H-2 Antigens/*chemistry/*immunology/metabolism ; Ligands ; Mice ; Mice, Transgenic ; Models, Molecular ; Mutation ; Oligopeptides/*chemistry/immunology/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/*immunology/metabolism ; Recombinant Proteins
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 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
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 1998-08-07
    Description: The small guanosine triphosphatases (GTPases) Cdc42 and Rac1 regulate E-cadherin-mediated cell-cell adhesion. IQGAP1, a target of Cdc42 and Rac1, was localized with E-cadherin and beta-catenin at sites of cell-cell contact in mouse L fibroblasts expressing E-cadherin (EL cells), and interacted with E-cadherin and beta-catenin both in vivo and in vitro. IQGAP1 induced the dissociation of alpha-catenin from a cadherin-catenin complex in vitro and in vivo. Overexpression of IQGAP1 in EL cells, but not in L cells expressing an E-cadherin-alpha-catenin chimeric protein, resulted in a decrease in E-cadherin-mediated cell-cell adhesive activity. Thus, IQGAP1, acting downstream of Cdc42 and Rac1, appears to regulate cell-cell adhesion through the cadherin-catenin pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuroda, S -- Fukata, M -- Nakagawa, M -- Fujii, K -- Nakamura, T -- Ookubo, T -- Izawa, I -- Nagase, T -- Nomura, N -- Tani, H -- Shoji, I -- Matsuura, Y -- Yonehara, S -- Kaibuchi, K -- New York, N.Y. -- Science. 1998 Aug 7;281(5378):832-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Signal Transduction, Nara Institute of Science and Technology, Ikoma 630-0101, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9694656" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cadherins/*metabolism ; *Cell Adhesion ; Cell Cycle Proteins/*metabolism ; Cell Membrane/metabolism ; Cytoskeletal Proteins/metabolism ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/*metabolism ; GTPase-Activating Proteins ; L Cells (Cell Line) ; Mice ; Mutation ; Proteins/*metabolism ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; *Trans-Activators ; alpha Catenin ; beta Catenin ; cdc42 GTP-Binding Protein ; rac GTP-Binding Proteins
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-18
    Description: During T cell activation, the engagement of costimulatory molecules is often crucial to the development of an effective immune response, but the mechanism by which this is achieved is not known. Here, it is shown that beads attached to the surface of a T cell translocate toward the interface shortly after the start of T cell activation. This movement appears to depend on myosin motor proteins and requires the engagement of the major costimulatory receptor pairs, B7-CD28 and ICAM-1-LFA-1. This suggests that the engagement of costimulatory receptors triggers an active accumulation of molecules at the interface of the T cell and the antigen-presenting cell, which then increases the overall amplitude and duration of T cell signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wulfing, C -- Davis, M M -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2266-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856952" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigens, CD/*metabolism ; Antigens, CD28/metabolism ; Antigens, CD86 ; Biotinylation ; CHO Cells ; Calcium/metabolism ; Cricetinae ; Cytoskeleton/*physiology ; Intercellular Adhesion Molecule-1/metabolism ; *Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; Microspheres ; Molecular Motor Proteins/physiology ; Myosins/physiology ; Phosphatidylinositol 3-Kinases/metabolism ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism/ultrastructure ; Tumor Cells, Cultured
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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: 1998-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sikorski, R -- Peters, R -- New York, N.Y. -- Science. 1998 May 15;280(5366):1101.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9616082" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Library ; Gene Targeting ; *Genetic Techniques ; Genetic Vectors ; Mice ; Mice, Knockout/*genetics ; Mutagenesis, Insertional ; Sequence Analysis, DNA ; *Stem Cells
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  • 6
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    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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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gearhart, J -- New York, N.Y. -- Science. 1998 Nov 6;282(5391):1061-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Gynecology and Obstetrics, Johns Hopkins Medicine, Baltimore, MD 21287, USA. gearhart@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9841453" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*cytology ; *Cell Culture Techniques ; Cell Differentiation ; *Cell Line ; Cell Lineage ; *Embryo Research ; Embryo, Mammalian/*cytology ; Federal Government ; Germ Cells/*cytology ; Government Regulation ; Guidelines as Topic ; Humans ; Major Histocompatibility Complex ; Mice ; Research Support as Topic ; Risk Assessment ; Stem Cell Transplantation ; Stem Cells/*cytology ; Transplantation Immunology ; United States
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chess, A -- New York, N.Y. -- Science. 1998 Mar 27;279(5359):2067-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. chess@wi.mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9537917" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; DNA Replication ; *Gene Expression Regulation ; Genes, Immunoglobulin ; Interleukin-2/*genetics ; Lymphocyte Activation ; Mice ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction ; Transcription, Genetic
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  • 9
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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〉Goldman, L R -- New York, N.Y. -- Science. 1998 Dec 4;282(5395):1825-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874633" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Environmental Exposure ; Environmental Pollutants/adverse effects ; Government Agencies ; Humans ; Lead/adverse effects ; Lead Poisoning/*prevention & control ; United States ; United States Environmental Protection Agency
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  • 10
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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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  • 11
    Publication Date: 1998-02-28
    Description: In the adult mouse, single and compound null mutations in the genes for retinoic acid receptor beta and retinoid X receptors beta and gamma resulted in locomotor defects related to dysfunction of the mesolimbic dopamine signaling pathway. Expression of the D1 and D2 receptors for dopamine was reduced in the ventral striatum of mutant mice, and the response of double null mutant mice to cocaine, which affects dopamine signaling in the mesolimbic system, was blunted. Thus, retinoid receptors are involved in the regulation of brain functions, and retinoic acid signaling defects may contribute to pathologies such as Parkinson's disease and schizophrenia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krezel, W -- Ghyselinck, N -- Samad, T A -- Dupe, V -- Kastner, P -- Borrelli, E -- Chambon, P -- New York, N.Y. -- Science. 1998 Feb 6;279(5352):863-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, Universite Louis Pasteur, College de France, Boite Postale 163, 67404 Illkirch Cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9452386" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cocaine/pharmacology ; Corpus Striatum/*metabolism ; Dimerization ; Dopamine/*metabolism ; Locomotion ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Motor Activity/drug effects ; Muscle, Skeletal/physiology ; Parkinson Disease/etiology ; Peripheral Nervous System/physiology ; Receptors, Dopamine D1/genetics/metabolism ; Receptors, Dopamine D2/genetics/metabolism ; Receptors, Retinoic Acid/genetics/*physiology ; Retinoid X Receptors ; Schizophrenia/etiology ; *Signal Transduction ; Transcription Factors/genetics/*physiology
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  • 12
    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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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goldman, L R -- Farland, W H -- New York, N.Y. -- Science. 1998 Jan 30;279(5351):640-1; author reply 641.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9471723" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Fishes ; *Food Contamination ; Humans ; Maximum Allowable Concentration ; Methylmercury Compounds/*adverse effects ; *Nutrition Policy ; Risk Assessment ; United States ; United States Environmental Protection Agency
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  • 14
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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〉Gough, M -- New York, N.Y. -- Science. 1998 Dec 4;282(5395):1823.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9874631" target="_blank"〉PubMed〈/a〉
    Keywords: 2,4,5-Trichlorophenoxyacetic Acid/adverse effects ; 2,4-Dichlorophenoxyacetic Acid/adverse effects ; Confidentiality/*legislation & jurisprudence ; Defoliants, Chemical ; Financing, Government ; Humans ; *Public Policy ; Research/*legislation & jurisprudence ; *Research Support as Topic ; Tetrachlorodibenzodioxin/adverse effects ; United States
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  • 15
    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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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clancy, C M -- Eisenberg, J M -- New York, N.Y. -- Science. 1998 Oct 9;282(5387):245-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Outcomes and Effectiveness Research, U.S. Department of Health and Human Services, Rockville, MD 20852, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9841388" target="_blank"〉PubMed〈/a〉
    Keywords: Activities of Daily Living ; Health Status ; Humans ; *Outcome Assessment (Health Care)/trends ; Patient Satisfaction ; Quality of Life ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steel, K P -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1870-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Institute of Hearing Research, Nottingham NG7 2RD, UK. karen@ihr.mrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9537904" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Carrier Proteins/genetics/physiology ; Cell Differentiation ; Chromosome Mapping ; Chromosomes, Human, Pair 5/genetics ; Deafness/*genetics ; Dyneins ; Female ; Gene Targeting ; Genes, Dominant ; Hair Cells, Auditory/physiology ; Hearing Loss, Sensorineural/*genetics ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Male ; Mice ; Myosins/genetics/physiology ; Pedigree ; Sequence Deletion ; Transcription Factor Brn-3C ; Transcription Factors/*genetics/metabolism/physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graves, B J -- New York, N.Y. -- Science. 1998 Feb 13;279(5353):1000-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84132, USA. graves@bioscience.utah.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9490475" target="_blank"〉PubMed〈/a〉
    Keywords: Ankyrins/chemistry ; Base Sequence ; Binding Sites ; DNA/chemistry/*metabolism ; DNA-Binding Proteins/*chemistry/*metabolism ; Dimerization ; GA-Binding Protein Transcription Factor ; Hydrogen Bonding ; Leucine Zippers ; Models, Molecular ; Protein Conformation ; Protein Structure, Secondary ; Transcription Factors/*chemistry/*metabolism ; Transcriptional Activation
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 1998 May 22;280(5367):1181.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9634393" target="_blank"〉PubMed〈/a〉
    Keywords: *Acquired Immunodeficiency Syndrome/history ; History, 20th Century ; National Institutes of Health (U.S.)/history/*organization & administration ; Research/history/*organization & administration ; United States
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-11-30
    Description: Fas ligand (CD95L) inhibits T cell function in immune-privileged organs such as the eye and testis, yet in most tissues CD95L expression induces potent inflammatory responses. With a stably transfected colon carcinoma cell line, CT26-CD95L, the molecular basis for these divergent responses was defined. When injected subcutaneously, rejection of CT26-CD95L was caused by neutrophils activated by CD95L. CT26-CD95L survived in the intraocular space because of the presence of transforming growth factor-beta (TGF-beta), which inhibited neutrophil activation. Providing TGF-beta to subcutaneous sites protected against tumor rejection. Thus, these cytokines together generate a microenvironment that promotes immunologic tolerance, which may aid in the amelioration of allograft rejection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, J J -- Sun, Y -- Nabel, G J -- New York, N.Y. -- Science. 1998 Nov 27;282(5394):1714-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, 1150 West Medical Center Drive, 4520 Medical Science Research Building I, Ann Arbor, MI 48109-0650, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9831564" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anterior Chamber ; Apoptosis ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Cytotoxicity, Immunologic ; Fas Ligand Protein ; Female ; Graft Rejection ; Humans ; Immune Tolerance ; Inflammation/*immunology ; Jurkat Cells ; Membrane Glycoproteins/*physiology ; Mice ; Mice, Inbred BALB C ; *Mitogen-Activated Protein Kinases ; Neoplasm Transplantation ; Neoplasms, Experimental/*immunology/pathology ; *Neutrophil Activation ; Neutrophils/immunology ; Transfection ; Transforming Growth Factor beta/pharmacology ; Tumor Cells, Cultured ; p38 Mitogen-Activated Protein Kinases
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, A -- New York, N.Y. -- Science. 1998 Mar 20;279(5358):1840-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9537898" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; *Exobiology/economics/organization & administration ; *Origin of Life ; Research Support as Topic ; United States ; *United States National Aeronautics and Space ; Administration/economics/organization & administration
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-01-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chesebro, B -- New York, N.Y. -- Science. 1998 Jan 2;279(5347):42-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Persistent Virus Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA. bchesebro@nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9441410" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid/chemistry ; Amyloidosis/metabolism ; Animals ; Cattle ; Creutzfeldt-Jakob Syndrome/epidemiology/*etiology/transmission ; Disease Susceptibility ; Encephalopathy, Bovine Spongiform/epidemiology/*etiology/transmission ; Gene Expression ; Great Britain/epidemiology ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Prion Diseases/*etiology/transmission ; Prions/chemistry/genetics/metabolism/*pathogenicity ; Virus Physiological Phenomena ; Viruses/pathogenicity
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, A -- New York, N.Y. -- Science. 1998 Feb 6;279(5352):794-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9480546" target="_blank"〉PubMed〈/a〉
    Keywords: *Budgets ; Financing, Government ; Government Agencies/*economics ; National Institutes of Health (U.S.)/*economics ; *Research Support as Topic ; Tobacco Industry ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gori, G B -- New York, N.Y. -- Science. 1998 Sep 18;281(5384):1805-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9776683" target="_blank"〉PubMed〈/a〉
    Keywords: *Conflict of Interest ; Humans ; Lung Neoplasms/etiology ; *Tobacco Industry ; Tobacco Smoke Pollution/*adverse effects ; United States ; *United States Environmental Protection Agency
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  • 25
    Publication Date: 1998-08-14
    Description: The breast and ovarian cancer susceptibility gene BRCA1 encodes a zinc finger protein of unknown function. Association of the BRCA1 protein with the DNA repair protein Rad51 and changes in the phosphorylation and cellular localization of the protein after exposure to DNA-damaging agents are consistent with a role for BRCA1 in DNA repair. Here, it is shown that mouse embryonic stem cells deficient in BRCA1 are defective in the ability to carry out transcription-coupled repair of oxidative DNA damage, and are hypersensitive to ionizing radiation and hydrogen peroxide. These results suggest that BRCA1 participates, directly or indirectly, in transcription-coupled repair of oxidative DNA damage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gowen, L C -- Avrutskaya, A V -- Latour, A M -- Koller, B H -- Leadon, S A -- CA40453/CA/NCI NIH HHS/ -- CA70490/CA/NCI NIH HHS/ -- IP50CA58223/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Aug 14;281(5379):1009-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Curriculum in Genetics and Molecular Biology and Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9703501" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; BRCA1 Protein/genetics/*physiology ; Cell Line ; DNA Damage ; *DNA Repair ; Hydrogen Peroxide ; Mice ; Oxidation-Reduction ; Stem Cells ; Thymine/analogs & derivatives/immunology/metabolism ; Transcription, Genetic ; Ultraviolet Rays
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  • 26
    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agnew, B -- New York, N.Y. -- Science. 1998 May 22;280(5367):1190.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9634398" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/*economics ; *Commerce ; International Cooperation ; *Investments ; Taiwan ; United States
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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〉Agnew, B -- New York, N.Y. -- Science. 1998 Feb 13;279(5353):976-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9490483" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Products ; Biotechnology ; Drug Approval ; Drug Industry ; *Research ; *Research Personnel ; Research Support as Topic ; United States ; United States Food and Drug Administration/*organization & administration
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  • 29
    Publication Date: 1998-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agosto, M -- Allan, J -- Benson, C -- Berger, E A -- Blumenthal, R -- Burton, D -- Clements, J -- Coffin, J -- Connor, R -- Cullen, B -- Desrosiers, R -- Dimitrov, D -- Doms, R -- Emerman, M -- Feinberg, M -- Fultz, P -- Gerard, C -- Gonsalves, G -- Haase, A -- Haigwood, N -- Hirsch, V -- Ho, D -- Hoxie, J A -- Hu, S L -- Zingale, D -- New York, N.Y. -- Science. 1998 May 8;280(5365):803, 804-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9599148" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines/immunology ; Acquired Immunodeficiency Syndrome/prevention & control ; *Clinical Trials as Topic ; HIV Envelope Protein gp120/immunology ; HIV-1/immunology ; Humans ; National Institutes of Health (U.S.) ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-06-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Steel, K P -- Brown, S D -- New York, N.Y. -- Science. 1998 May 29;280(5368):1403.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Institute of Hearing Research, University Park, Nottingham NG7 2RD, UK. karen@ihr.mrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9634418" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/physiology ; Animals ; Cilia/physiology ; Deafness/*genetics ; Dyneins ; Extracellular Matrix Proteins/*genetics/physiology ; GPI-Linked Proteins ; Hair Cells, Auditory/physiology/ultrastructure ; Hearing ; Humans ; Membrane Glycoproteins/*genetics/physiology ; Mice ; Mice, Mutant Strains ; Mutation ; Myosin Heavy Chains/genetics/physiology ; Myosins/*genetics/physiology ; Tectorial Membrane/physiology
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-12-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Oct 23;282(5389):652-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9841420" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/genetics ; Budgets ; Crops, Agricultural/*genetics ; DNA Transposable Elements ; Financing, Government ; Gene Expression Regulation, Plant ; *Genome, Plant ; International Cooperation ; Mutagenesis, Insertional ; Oryza/genetics ; *Physical Chromosome Mapping/economics ; *Research Support as Topic ; *Sequence Analysis, DNA/economics ; United States ; Zea mays/*genetics
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  • 32
    Publication Date: 1998-05-09
    Description: Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to Gq class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to Gq.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Akhter, S A -- Luttrell, L M -- Rockman, H A -- Iaccarino, G -- Lefkowitz, R J -- Koch, W J -- HL-03041/HL/NHLBI NIH HHS/ -- HL-09436/HL/NHLBI NIH HHS/ -- HL-16037/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 Apr 24;280(5363):574-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9554846" target="_blank"〉PubMed〈/a〉
    Keywords: Angiotensin II/pharmacology ; Animals ; Atrial Natriuretic Factor/genetics ; COS Cells ; Diglycerides/metabolism ; Enzyme Activation ; GTP-Binding Proteins/antagonists & inhibitors/genetics/*metabolism ; Gene Expression Regulation ; Gene Targeting ; Hypertrophy, Left Ventricular/*metabolism/prevention & control ; Inositol Phosphates/metabolism ; Mice ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 1/metabolism ; Myocardium/*metabolism ; Peptide Fragments/genetics/metabolism ; Phenylephrine/pharmacology ; Receptors, Adrenergic, alpha/*metabolism ; Signal Transduction ; Transfection ; Transgenes ; Ventricular Pressure
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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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clarkson, T -- Cox, C -- Davidson, P W -- Myers, G J -- New York, N.Y. -- Science. 1998 Jan 23;279(5350):459, 461.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9454336" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Child ; *Fishes ; *Food Contamination ; Humans ; Iraq ; Maximum Allowable Concentration ; Methylmercury Compounds/administration & dosage/*adverse effects/analysis ; *Nutrition Policy ; Seychelles ; United States ; United States Environmental Protection Agency ; World Health Organization
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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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  • 36
    Publication Date: 1998-11-13
    Description: Self tolerance is acquired by the developing immune system. As reported here, particular properties of the neonatal tissue contribute to this process. Neonatal skin, but not adult skin, was accessible for naive CD8 T cells. In mouse bone marrow chimeras generated at different ages, recent thymic emigrants were tolerized to a skin-expressed major histocompatibility complex class I antigen only during a neonatal period but not during adulthood. Blockade of T cell migration neonatally prevented tolerance induction. Thus, T cell trafficking through nonlymphoid tissues in the neonate is crucial for the establishment of self tolerance to sessile, skin-expressed antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alferink, J -- Tafuri, A -- Vestweber, D -- Hallmann, R -- Hammerling, G J -- Arnold, B -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1338-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tumor Immunology Program, German Cancer Research Center, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Antigen Presentation ; Bone Marrow Transplantation ; CD8-Positive T-Lymphocytes/*immunology ; Cell Movement ; Graft Rejection ; H-2 Antigens/*immunology ; Keratinocytes/immunology ; Mice ; Mice, Transgenic ; Neoplasm Transplantation ; Neoplasms, Experimental/immunology ; Self Tolerance/*immunology ; Skin/*immunology ; Skin Transplantation ; T-Lymphocytes/*immunology ; Thymus Gland/immunology ; Transplantation Chimera
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-05-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, R -- New York, N.Y. -- Science. 1998 Apr 17;280(5362):372.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9575079" target="_blank"〉PubMed〈/a〉
    Keywords: *Academies and Institutes/economics/organization & administration ; *Drug Industry/economics ; Hungary ; *Pharmaceutical Preparations ; United States
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-11-13
    Description: Human reovirus requires an activated Ras signaling pathway for infection of cultured cells. To investigate whether this property can be exploited for cancer therapy, severe combined immune deficient mice bearing tumors established from v-erbB-transformed murine NIH 3T3 cells or human U87 glioblastoma cells were treated with the virus. A single intratumoral injection of virus resulted in regression of tumors in 65 to 80 percent of the mice. Treatment of immune-competent C3H mice bearing tumors established from ras-transformed C3H-10T1/2 cells also resulted in tumor regression, although a series of injections were required. These results suggest that, with further work, reovirus may have applicability in the treatment of cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coffey, M C -- Strong, J E -- Forsyth, P A -- Lee, P W -- New York, N.Y. -- Science. 1998 Nov 13;282(5392):1332-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology Research Group and Department of Microbiology and Infectious Diseases, University of Calgary Health Science Centre, Calgary, Alberta, T2N 4N1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9812900" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Antibodies, Viral/immunology ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Cell Line, Transformed ; Genes, erbB ; *Genes, ras ; Humans ; Male ; Mammalian orthoreovirus 3/immunology/*physiology ; Mice ; Mice, Inbred C3H ; Mice, SCID ; Neoplasm Transplantation ; Neoplasms, Experimental/metabolism/pathology/*therapy/virology ; Signal Transduction ; Tumor Cells, Cultured ; Virus Replication ; ras Proteins/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1624.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9518372" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/*legislation & jurisprudence ; Conservation of Natural Resources/*legislation & jurisprudence ; Northwestern United States ; Public Policy ; Technology Transfer ; United States ; United States Environmental Protection Agency
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-03-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Mar 6;279(5356):1456.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9508720" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Cells/cytology/*physiology ; Bone Marrow Transplantation ; Cell Differentiation ; Humans ; Mice ; Mice, Transgenic ; Muscle, Skeletal/cytology/pathology/*physiology ; Muscular Dystrophies/pathology/*therapy ; Muscular Dystrophy, Animal/pathology/therapy ; *Regeneration ; Stem Cells/*physiology ; Stromal Cells/physiology
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-02-07
    Description: In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides-one containing an alphav integrin-binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif-enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arap, W -- Pasqualini, R -- Ruoslahti, E -- CA30199/CA/NCI NIH HHS/ -- CA62042/CA/NCI NIH HHS/ -- CA74238-01/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):377-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430587" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Antineoplastic Agents/*administration & dosage/therapeutic use/toxicity ; Bacteriophages ; Coronary Vessels/drug effects ; Doxorubicin/*administration & dosage/*analogs & ; derivatives/metabolism/therapeutic use/toxicity ; *Drug Carriers ; Heart/drug effects ; Humans ; Integrin alphaV ; Integrins/metabolism ; Liver/blood supply/drug effects ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental/*blood supply/*drug therapy/pathology ; Oligopeptides/*administration & dosage/metabolism/therapeutic use/toxicity ; Peptide Library ; Random Allocation ; Transplantation, Heterologous ; Tumor Cells, Cultured
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Aug 20;285(5431):1200-1, 1203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10484727" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Acetyltransferases/chemistry/metabolism ; Animals ; Cell Cycle Proteins/chemistry/metabolism ; Chromatin/chemistry/*metabolism/*ultrastructure ; *Gene Expression Regulation ; Histone Acetyltransferases ; Histones/*metabolism ; Methylation ; *Mitosis ; Phosphorylation ; Protein Structure, Secondary ; Protein-Arginine N-Methyltransferases/metabolism ; Transcription Factors ; p300-CBP Transcription Factors
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-08
    Description: Postdoctoral appointments can have different functions and meanings, depending on the field and whether the postdoc is a man or a woman. The Ph.D.'s-Ten Years Later study confirmed that in biochemistry, the postdoc, not the Ph.D., has become the general proving ground for excellence both in academia and industry. Because they spent a longer time in these "mandatory" postdocs, biochemists had the largest proportion of untenured faculty 10 to 13 years after the Ph. D. In mathematics, where substantially fewer postdoctoral positions are available, Ph.D.'s taking postdocs are more likely to obtain faculty positions, but this is true only for men. University administrators should be accountable for monitoring the total time spent in these positions and should provide administrative assistance for skills training, career growth, and the job search. In addition, creative solutions concerning the dual-career couple phenomenon are necessary.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nerad, M -- Cerny, J -- New York, N.Y. -- Science. 1999 Sep 3;285(5433):1533-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate Division, University of California, Berkeley, 424 Sproul Hall, Berkeley, CA 94720-5900, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10477510" target="_blank"〉PubMed〈/a〉
    Keywords: *Biochemistry/education ; *Career Mobility ; *Education, Graduate ; Employment ; Faculty ; *Fellowships and Scholarships ; Female ; Humans ; Male ; *Mathematics ; Salaries and Fringe Benefits ; Societies, Scientific ; Time Factors ; United States ; Universities
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-10-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Madia, W J -- New York, N.Y. -- Science. 1998 Oct 2;282(5386):45.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9786793" target="_blank"〉PubMed〈/a〉
    Keywords: Chlorine ; *Environmental Pollutants ; Government Agencies ; National Institutes of Health (U.S.) ; *Research ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence ; Water Supply
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, J -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2175-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9890822" target="_blank"〉PubMed〈/a〉
    Keywords: Budgets ; Cartilage ; *Complementary Therapies/economics/organization & administration ; Controlled Clinical Trials as Topic ; Humans ; Lung Neoplasms/therapy ; National Institutes of Health (U.S.)/economics/*organization & administration ; Research Support as Topic ; Tissue Extracts/therapeutic use ; United States
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  • 46
    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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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, I -- New York, N.Y. -- Science. 1999 Aug 13;285(5430):999.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10475850" target="_blank"〉PubMed〈/a〉
    Keywords: Biotechnology/history ; Genetics, Medical/history ; Genome, Human ; History, 20th Century ; Humans ; United States
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  • 48
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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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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-01-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1998 Jan 9;279(5348):176-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9446222" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*chemistry ; Binding Sites ; Cell Division ; Crystallization ; Crystallography/*methods ; Crystallography, X-Ray ; *Cytoskeletal Proteins ; GTP-Binding Proteins/chemistry ; Guanosine Triphosphate/metabolism ; Microtubules/chemistry ; Models, Molecular ; *Protein Conformation ; Protein Structure, Secondary ; Tubulin/*chemistry
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  • 50
    Publication Date: 1998-10-17
    Description: The angiopoietins and members of the vascular endothelial growth factor (VEGF) family are the only growth factors thought to be largely specific for vascular endothelial cells. Targeted gene inactivation studies in mice have shown that VEGF is necessary for the early stages of vascular development and that angiopoietin-1 is required for the later stages of vascular remodeling. Here it is shown that transgenic overexpression of angiopoietin-1 in the skin of mice produces larger, more numerous, and more highly branched vessels. These results raise the possibility that angiopoietins can be used, alone or in combination with VEGF, to promote therapeutic angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suri, C -- McClain, J -- Thurston, G -- McDonald, D M -- Zhou, H -- Oldmixon, E H -- Sato, T N -- Yancopoulos, G D -- HL-24136/HL/NHLBI NIH HHS/ -- HL-59157/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1998 Oct 16;282(5388):468-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9774272" target="_blank"〉PubMed〈/a〉
    Keywords: Angiopoietin-1 ; Animals ; Capillaries/anatomy & histology/ultrastructure ; Endothelial Growth Factors/genetics/physiology ; Endothelium, Vascular/ultrastructure ; Gene Expression ; Keratinocytes/metabolism ; Lymphokines/genetics/physiology ; Membrane Glycoproteins/genetics/*physiology ; Mice ; Mice, Transgenic ; *Neovascularization, Physiologic ; Skin/*blood supply/metabolism ; Transgenes ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Venules/anatomy & histology/ultrastructure
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  • 51
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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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Langan, P -- Schoenborn, B P -- New York, N.Y. -- Science. 1999 Nov 5;286(5442):1089.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610521" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography/*instrumentation ; *Neutrons ; Proteins/*chemistry ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1998-10-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, J -- New York, N.Y. -- Science. 1998 Sep 18;281(5384):1779.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9776674" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*economics ; Biology/*education ; *Training Support ; United States ; Universities/*economics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Laver, W G -- New York, N.Y. -- Science. 1999 Jun 25;284(5423):2089.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10409063" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallization ; Neuraminidase/*chemistry ; *Space Flight ; *Spacecraft ; United States ; United States National Aeronautics and Space Administration ; *Weightlessness
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  • 55
    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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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawler, C -- Erbisch, F -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):33-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9917260" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biotechnology ; Mice ; Mice, Transgenic ; *Patents as Topic ; Plants, Genetically Modified/*genetics ; United States
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  • 57
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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〉Shapiro, H T -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2065.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523197" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; *Bioethical Issues ; Embryo Research ; Embryo, Mammalian/*cytology ; Ethics Committees ; Financing, Government ; Government Regulation ; Humans ; Private Sector ; *Public Policy ; Research/*standards ; Research Support as Topic ; *Stem Cells ; United States
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colvin, M -- New York, N.Y. -- Science. 1999 May 28;284(5419):1480.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Duke Comprehensive Cancer Center, Durham, NC 27710, USA. colvi003@mc.duke.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10383327" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry, Pharmaceutical/history ; Drug Design ; History, 20th Century ; Nobel Prize ; United States
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Apr 30;284(5415):723, 725.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10336390" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Breast Neoplasms/*genetics/pathology ; *Disease Models, Animal ; Female ; *Genes, BRCA1 ; Genes, p53 ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Animal/*genetics/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Mutation
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wickelgren, I -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1826-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610569" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/cytology ; Cell Differentiation ; Cell Survival ; Embryo, Mammalian ; Mice ; Neurons/cytology ; Oligodendroglia/cytology ; Rats ; Spinal Cord/cytology/*physiology ; Spinal Cord Injuries/*therapy ; *Stem Cell Transplantation ; Stem Cells/cytology
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  • 61
    Publication Date: 1999-11-27
    Description: X-ray crystal structures of three species related to the oxidative half of the reaction of the copper-containing quinoprotein amine oxidase from Escherichia coli have been determined. Crystals were freeze-trapped either anaerobically or aerobically after exposure to substrate, and structures were determined to resolutions between 2.1 and 2.4 angstroms. The oxidation state of the quinone cofactor was investigated by single-crystal spectrophotometry. The structures reveal the site of bound dioxygen and the proton transfer pathways involved in oxygen reduction. The quinone cofactor is regenerated from the iminoquinone intermediate by hydrolysis involving Asp383, the catalytic base in the reductive half-reaction. Product aldehyde inhibits the hydrolysis, making release of product the rate-determining step of the reaction in the crystal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilmot, C M -- Hajdu, J -- McPherson, M J -- Knowles, P F -- Phillips, S E -- New York, N.Y. -- Science. 1999 Nov 26;286(5445):1724-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Astbury Centre for Structural Molecular Biology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10576737" target="_blank"〉PubMed〈/a〉
    Keywords: Aerobiosis ; Amine Oxidase (Copper-Containing)/*chemistry/*metabolism ; Anaerobiosis ; Aspartic Acid/chemistry/metabolism ; Binding Sites ; Catalysis ; Copper/*metabolism ; Crystallography, X-Ray ; Dihydroxyphenylalanine/*analogs & derivatives/chemistry/metabolism ; Dimerization ; Electrons ; Escherichia coli/enzymology ; Hydrogen Bonding ; Nitric Oxide/metabolism ; Oxidation-Reduction ; Oxygen/*metabolism ; Phenethylamines/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protons ; Spectrum Analysis
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  • 62
    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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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Av-Gay, Y -- New York, N.Y. -- Science. 1999 Jun 4;284(5420):1621.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10383337" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteria/*genetics/pathogenicity ; *Biotechnology ; *Containment of Biohazards ; Ecosystem ; *Genetic Engineering ; Guidelines as Topic ; Humans ; United States ; Viruses/*genetics/pathogenicity
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, I A -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1867-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. wilson@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610577" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/*chemistry/immunology/metabolism ; Binding Sites ; CD4-Positive T-Lymphocytes/immunology/metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism ; Crystallography, X-Ray ; Histocompatibility Antigens Class I/chemistry/immunology/metabolism ; Histocompatibility Antigens Class II/*chemistry/immunology/metabolism ; Mice ; Models, Molecular ; Peptides/chemistry/immunology/metabolism ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/immunology/metabolism
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  • 65
    Publication Date: 1999-12-11
    Description: Natural antibodies are often dismissed from immunological analysis as "background," but they may play an important role in conferring immunity against infections. In antibody-free mice infected with various viruses or with Listeria monocytogenes, viral or bacterial titers in peripheral organs, including the kidney and brain, were 10 to 100 times greater than in antibody-competent mice (and enhanced their susceptibility to some infections), and titers in secondary lymphoid organs were 10 to 100 times lower than in antibody-competent mice. Thus, natural antibodies play a crucial role by preventing pathogen dissemination to vital organs and by improving immunogenicity through enhanced antigen-trapping in secondary lymphoid organs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ochsenbein, A F -- Fehr, T -- Lutz, C -- Suter, M -- Brombacher, F -- Hengartner, H -- Zinkernagel, R M -- New York, N.Y. -- Science. 1999 Dec 10;286(5447):2156-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10591647" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Bacterial/blood/immunology ; Antibodies, Viral/blood/immunology ; Bacterial Infections/*immunology/microbiology ; Germ-Free Life ; *Immunity, Innate ; Immunoglobulin M/blood/*immunology ; Kidney/microbiology/virology ; Listeria monocytogenes/immunology/physiology ; Listeriosis/immunology ; Lymphocytic choriomeningitis virus/immunology/physiology ; Lymphoid Tissue/immunology/microbiology/virology ; Mice ; Mice, Inbred C57BL ; Neutralization Tests ; Rhabdoviridae Infections/immunology/virology ; Specific Pathogen-Free Organisms ; Spleen/microbiology/virology ; Vaccinia virus/immunology/physiology ; Vesicular stomatitis Indiana virus/immunology/physiology ; Virus Diseases/*immunology/virology ; Virus Replication
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Curry, M -- Hazard-Daniel, A -- Daniel, H J -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1854-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610573" target="_blank"〉PubMed〈/a〉
    Keywords: *Dietary Supplements/adverse effects ; Drug Prescriptions ; Drug-Related Side Effects and Adverse Reactions ; *Legislation, Drug ; *Legislation, Food ; United States ; United States Food and Drug Administration
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  • 67
    Publication Date: 1999-10-09
    Description: CD2-associated protein (CD2AP) is an 80-kilodalton protein that is critical for stabilizing contacts between T cells and antigen-presenting cells. In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells. Knockout mice exhibited defects in epithelial cell foot processes, accompanied by mesangial cell hyperplasia and extracellular matrix deposition. Supporting a role for CD2AP in the specialized cell junction known as the slit diaphragm, CD2AP associated with nephrin, the primary component of the slit diaphragm.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shih, N Y -- Li, J -- Karpitskii, V -- Nguyen, A -- Dustin, M L -- Kanagawa, O -- Miner, J H -- Shaw, A S -- New York, N.Y. -- Science. 1999 Oct 8;286(5438):312-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology and Department of Pathology, Washington University, Saint Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10514378" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Basement Membrane/ultrastructure ; Cytoskeletal Proteins ; Epithelial Cells/metabolism/ultrastructure ; Extracellular Matrix Proteins/metabolism ; Glomerular Mesangium/metabolism/ultrastructure ; Intercellular Junctions/metabolism/ultrastructure ; Kidney Glomerulus/blood supply/*metabolism/*ultrastructure ; Lymphocyte Activation ; Membrane Proteins ; Mice ; Mice, Knockout ; Microscopy, Electron ; Nephrotic Syndrome/*congenital/genetics/metabolism/pathology ; Proteins/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes/immunology
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  • 68
    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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  • 69
    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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  • 70
    Publication Date: 1999-05-29
    Description: Endoglin is a transforming growth factor-beta (TGF-beta) binding protein expressed on the surface of endothelial cells. Loss-of-function mutations in the human endoglin gene ENG cause hereditary hemorrhagic telangiectasia (HHT1), a disease characterized by vascular malformations. Here it is shown that by gestational day 11.5, mice lacking endoglin die from defective vascular development. However, in contrast to mice lacking TGF-beta, vasculogenesis was unaffected. Loss of endoglin caused poor vascular smooth muscle development and arrested endothelial remodeling. These results demonstrate that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, D Y -- Sorensen, L K -- Brooke, B S -- Urness, L D -- Davis, E C -- Taylor, D G -- Boak, B B -- Wendel, D P -- K08 HL03490-03/HL/NHLBI NIH HHS/ -- T35 HL07744-06/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1999 May 28;284(5419):1534-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Human Molecular Biology and Genetics, Department of Human Genetics, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-5330, USA. dean.li@hci.utah.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10348742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD ; Antigens, CD31/analysis ; Blood Vessels/cytology/*embryology/metabolism ; Cell Differentiation ; Crosses, Genetic ; Endothelium, Vascular/cytology/*embryology/metabolism ; Female ; Gene Targeting ; In Situ Hybridization ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron ; Muscle, Smooth, Vascular/cytology/*embryology ; *Neovascularization, Physiologic ; Receptors, Cell Surface ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Vascular Cell Adhesion Molecule-1/genetics/*physiology ; Yolk Sac/ultrastructure
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  • 71
    Publication Date: 1999-07-20
    Description: Graft versus host disease, an alloimmune attack on host tissues mounted by donor T cells, is the most important toxicity of allogeneic bone marrow transplantation. The mechanism by which allogeneic T cells are initially stimulated is unknown. In a murine allogeneic bone marrow transplantation model it was found that, despite the presence of numerous donor antigen-presenting cells, only host-derived antigen-presenting cells initiated graft versus host disease. Thus, strategies for preventing graft versus host disease could be developed that are based on inactivating host antigen-presenting cells. Such strategies could expand the safety and application of allogeneic bone marrow transplantation in treatment of common genetic and neoplastic diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shlomchik, W D -- Couzens, M S -- Tang, C B -- McNiff, J -- Robert, M E -- Liu, J -- Shlomchik, M J -- Emerson, S G -- P50HL-54516/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1999 Jul 16;285(5426):412-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10411505" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/*immunology ; Bone Marrow Transplantation/adverse effects/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Dendritic Cells/immunology ; Graft vs Host Disease/immunology/*prevention & control ; H-2 Antigens/immunology ; Lymph Nodes/immunology ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Mice, Knockout ; Minor Histocompatibility Antigens/immunology ; Spleen/immunology ; Transplantation Chimera
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  • 72
    Publication Date: 1999-04-09
    Description: Imprinted genes display parent-of-origin-dependent monoallelic expression that apparently regulates complex mammalian traits, including growth and behavior. The Peg3 gene is expressed in embryos and the adult brain from the paternal allele only. A mutation in the Peg3 gene resulted in growth retardation, as well as a striking impairment of maternal behavior that frequently resulted in death of the offspring. This result may be partly due to defective neuronal connectivity, as well as reduced oxytocin neurons in the hypothalamus, because mutant mothers were deficient in milk ejection. This study provides further insights on the evolution of epigenetic regulation of imprinted gene dosage in modulating mammalian growth and behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Keverne, E B -- Aparicio, S A -- Ishino, F -- Barton, S C -- Surani, M A -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):330-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome CRC Institute of Cancer and Developmental Biology, and Physiological Laboratory, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195900" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; Brain/metabolism ; Crosses, Genetic ; Female ; Gene Expression ; Gene Targeting ; *Genomic Imprinting ; *Growth ; Hypothalamus/cytology/metabolism ; Kruppel-Like Transcription Factors ; Lactation ; Male ; *Maternal Behavior ; Mice ; Mutation ; Neural Pathways ; Neurons/metabolism ; Oxytocin/metabolism ; Phenotype ; *Protein Kinases ; Proteins/genetics/*physiology ; *Transcription Factors ; *Weight Gain
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-04-30
    Description: The ability of the GroEL chaperonin to unfold a protein trapped in a misfolded condition was detected and studied by hydrogen exchange. The GroEL-induced unfolding of its substrate protein is only partial, requires the complete chaperonin system, and is accomplished within the 13 seconds required for a single system turnover. The binding of nucleoside triphosphate provides the energy for a single unfolding event; multiple turnovers require adenosine triphosphate hydrolysis. The substrate protein is released on each turnover even if it has not yet refolded to the native state. These results suggest that GroEL helps partly folded but blocked proteins to fold by causing them first to partially unfold. The structure of GroEL seems well suited to generate the nonspecific mechanical stretching force required for forceful protein unfolding.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427652/" 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/PMC3427652/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shtilerman, M -- Lorimer, G H -- Englander, S W -- GM31847/GM/NIGMS NIH HHS/ -- R01 GM031847/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Apr 30;284(5415):822-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10221918" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Adenylyl Imidodiphosphate/metabolism ; Binding Sites ; Chaperonin 10/chemistry/metabolism/physiology ; Chaperonin 60/chemistry/metabolism/*physiology ; Hydrogen/chemistry/metabolism ; Models, Molecular ; Protein Binding ; Protein Conformation ; *Protein Folding ; Protein Structure, Secondary ; Ribulose-Bisphosphate Carboxylase/*chemistry/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 74
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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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  • 75
    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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  • 76
    Publication Date: 1999-07-03
    Description: Lymphocyte development is critically influenced by self-antigens. T cells are subject to both positive and negative selection, depending on their degree of self-reactivity. Although B cells are subject to negative selection, it has been difficult to test whether self-antigen plays any positive role in B cell development. A murine model system of naturally generated autoreactive B cells with a germ line gene-encoded specificity for the Thy-1 (CD90) glycoprotein was developed, in which the presence of self-antigen promotes B cell accumulation and serum autoantibody secretion. Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayakawa, K -- Asano, M -- Shinton, S A -- Gui, M -- Allman, D -- Stewart, C L -- Silver, J -- Hardy, R R -- New York, N.Y. -- Science. 1999 Jul 2;285(5424):113-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA. K_Hayakawa@fccc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10390361" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/immunology ; Animals ; Antigens, CD5/analysis ; Antigens, Thy-1/*immunology ; Autoantibodies/*biosynthesis/blood/immunology ; Autoantigens/*immunology ; B-Lymphocyte Subsets/*immunology ; Genes, Immunoglobulin ; Hybridomas ; Immunity, Innate ; Immunologic Surveillance ; Mice ; Mice, SCID ; Mice, Transgenic ; Receptors, Antigen, B-Cell/immunology ; Signal Transduction ; T-Lymphocytes/immunology
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  • 77
    Publication Date: 1999-04-09
    Description: Phosphorylation of inhibitor of kappa B (IkappaB) proteins is an important step in the activation of the transcription nuclear factor kappa B (NF-kappaB) and requires two IkappaB kinases, IKK1 (IKKalpha) and IKK2 (IKKbeta). Mice that are devoid of the IKK2 gene had extensive liver damage from apoptosis and died as embryos, but these mice could be rescued by the inactivation of the gene encoding tumor necrosis factor receptor 1. Mouse embryonic fibroblast cells that were isolated from IKK2-/- embryos showed a marked reduction in tumor necrosis factor-alpha (TNF-alpha)- and interleukin-1alpha-induced NF-kappaB activity and an enhanced apoptosis in response to TNF-alpha. IKK1 associated with NF-kappaB essential modulator (IKKgamma/IKKAP1), another component of the IKK complex. These results show that IKK2 is essential for mouse development and cannot be substituted with IKK1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Q -- Van Antwerp, D -- Mercurio, F -- Lee, K F -- Verma, I M -- New York, N.Y. -- Science. 1999 Apr 9;284(5412):321-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute, La Jolla, CA 92037, USA. Signal Pharmaceuticals, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10195897" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Line ; DNA-Binding Proteins/metabolism ; Embryonic and Fetal Development ; Gene Targeting ; I-kappa B Kinase ; I-kappa B Proteins ; Interleukin-1/pharmacology ; Liver/cytology/*embryology ; Mice ; NF-kappa B/metabolism ; Phosphorylation ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Receptors, Tumor Necrosis Factor/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Sequence Deletion ; Signal Transduction ; Transcription Factor RelA ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 78
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    Unknown
    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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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-12-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sikorski, R -- Peters, R -- New York, N.Y. -- Science. 1999 Nov 19;286(5444):1498.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10610553" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Cells/*cytology ; Cell Differentiation ; Cell Separation ; Dystrophin/biosynthesis ; Female ; *Hematopoietic Stem Cell Transplantation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Muscle, Skeletal/*cytology/metabolism ; *Stem Cell Transplantation ; Stem Cells/*cytology
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  • 80
    Publication Date: 1999-09-18
    Description: Antithrombin, a member of the serpin family, functions as an inhibitor of thrombin and other enzymes. Cleavage of the carboxyl-terminal loop of antithrombin induces a conformational change in the molecule. Here it is shown that the cleaved conformation of antithrombin has potent antiangiogenic and antitumor activity in mouse models. The latent form of intact antithrombin, which is similar in conformation to the cleaved molecule, also inhibited angiogenesis and tumor growth. These data provide further evidence that the clotting and fibrinolytic pathways are directly involved in the regulation of angiogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Reilly, M S -- Pirie-Shepherd, S -- Lane, W S -- Folkman, J -- P01-CA45548/CA/NCI NIH HHS/ -- R01-CA64481/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 17;285(5435):1926-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Children's Hospital, Departments of Surgery and Cellular Biology, Harvard Microchemistry Facility, 16 Divinity Avenue, Cambridge, MA 02138, USA. oreilly@hub.tch.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10489375" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/chemistry/isolation & purification/metabolism/*pharmacology ; Antithrombins/chemistry/isolation & purification/metabolism/*pharmacology ; Carcinoma, Small Cell/blood supply/drug therapy ; Cell Line ; Culture Media, Conditioned ; Drug Screening Assays, Antitumor ; Humans ; Lung Neoplasms/blood supply/drug therapy ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Neovascularization, Pathologic/*drug therapy ; Peptide Fragments/chemistry/metabolism/pharmacology ; Protein Conformation ; Tumor Cells, Cultured
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  • 81
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, M -- New York, N.Y. -- Science. 1999 Apr 16;284(5413):410.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10232978" target="_blank"〉PubMed〈/a〉
    Keywords: Academies and Institutes/*organization & administration ; Developing Countries ; History, 20th Century ; *Immunization Programs ; Korea ; United Nations ; United States ; *Vaccines ; World Health Organization
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  • 82
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hederstedt, L -- New York, N.Y. -- Science. 1999 Jun 18;284(5422):1941-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Lund University, Lund, Sweden. Lars.Hederstedt@mikrbiol.lu.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10400536" target="_blank"〉PubMed〈/a〉
    Keywords: Anaerobiosis ; Bacillus subtilis/enzymology ; Binding Sites ; Cell Membrane/enzymology ; Crystallography, X-Ray ; Dimerization ; Electron Transport ; *Energy Metabolism ; Escherichia coli/*enzymology ; Evolution, Molecular ; Fumarates/metabolism ; Mitochondria/enzymology ; Oxidation-Reduction ; Oxygen Consumption ; Protein Conformation ; Protein Structure, Secondary ; Succinate Dehydrogenase/*chemistry/*metabolism ; Succinic Acid/metabolism
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  • 83
    Publication Date: 1999-09-11
    Description: To characterize the mechanism by which receptors propagate conformational changes across membranes, nitroxide spin labels were attached at strategic positions in the bacterial aspartate receptor. By collecting the electron paramagnetic resonance spectra of these labeled receptors in the presence and absence of the ligand aspartate, ligand binding was shown to generate an approximately 1 angstrom intrasubunit piston-type movement of one transmembrane helix downward relative to the other transmembrane helix. The receptor-associated phosphorylation cascade proteins CheA and CheW did not alter the ligand-induced movement. Because the piston movement is very small, the ability of receptors to produce large outcomes in response to stimuli is caused by the ability of the receptor-coupled enzymes to detect small changes in the conformation of the receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ottemann, K M -- Xiao, W -- Shin, Y K -- Koshland, D E Jr -- DK09765/DK/NIDDK NIH HHS/ -- GM51290/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1751-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology and Department of Chemistry, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10481014" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/*metabolism ; Bacterial Proteins/metabolism ; Cell Membrane/*metabolism ; Chemotaxis ; Dimerization ; Electron Spin Resonance Spectroscopy ; Escherichia coli/metabolism ; *Escherichia coli Proteins ; Fourier Analysis ; Ligands ; Lipid Bilayers ; Membrane Proteins/metabolism ; Methylation ; *Models, Biological ; Mutagenesis ; Phosphorylation ; Protein Conformation ; Protein Kinases/metabolism ; Protein Structure, Secondary ; Receptors, Amino Acid/*chemistry/genetics/*metabolism ; *Signal Transduction ; Spin Labels
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  • 84
    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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  • 85
    Publication Date: 1999-05-13
    Description: Salmonella typhimurium lacking DNA adenine methylase (Dam) were fully proficient in colonization of mucosal sites but showed severe defects in colonization of deeper tissue sites. These Dam- mutants were totally avirulent and were effective as live vaccines against murine typhoid fever. Dam regulated the expression of at least 20 genes known to be induced during infection; a subset of these genes are among those activated by the PhoP global virulence regulator. PhoP, in turn, affected Dam methylation at specific genomic sites, as evidenced by alterations in DNA methylation patterns. Dam inhibitors are likely to have broad antimicrobial action, and Dam- derivatives of these pathogens may serve as live attenuated vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heithoff, D M -- Sinsheimer, R L -- Low, D A -- Mahan, M J -- AI23348/AI/NIAID NIH HHS/ -- AI36373/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1999 May 7;284(5416):967-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320378" target="_blank"〉PubMed〈/a〉
    Keywords: Adenine/metabolism ; Animals ; Bacterial Proteins/metabolism ; *Bacterial Vaccines ; *DNA Methylation ; DNA, Bacterial/metabolism ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Lethal Dose 50 ; Methylation ; Mice ; Mice, Inbred BALB C ; Mutation ; Peyer's Patches/microbiology ; Salmonella Infections, Animal/immunology/*microbiology/prevention & control ; Salmonella typhimurium/*enzymology/genetics/immunology/*pathogenicity ; Site-Specific DNA-Methyltransferase (Adenine-Specific)/antagonists & ; inhibitors/genetics/*metabolism ; Vaccines, Attenuated ; Virulence/genetics
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  • 86
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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〉Dawson, G R -- Flint, J -- Wilkinson, L S -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2068; author reply 2069-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523201" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Laboratory/genetics ; *Behavior, Animal ; Confounding Factors (Epidemiology) ; Genetics, Behavioral/*methods ; Handling (Psychology) ; Mice ; Reproducibility of Results
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  • 87
    Publication Date: 1999-08-14
    Description: Isoleucyl-transfer RNA (tRNA) synthetase (IleRS) joins Ile to tRNA(Ile) at its synthetic active site and hydrolyzes incorrectly acylated amino acids at its editing active site. The 2.2 angstrom resolution crystal structure of Staphylococcus aureus IleRS complexed with tRNA(Ile) and Mupirocin shows the acceptor strand of the tRNA(Ile) in the continuously stacked, A-form conformation with the 3' terminal nucleotide in the editing active site. To position the 3' terminus in the synthetic active site, the acceptor strand must adopt the hairpinned conformation seen in tRNA(Gln) complexed with its synthetase. The amino acid editing activity of the IleRS may result from the incorrect products shuttling between the synthetic and editing active sites, which is reminiscent of the editing mechanism of DNA polymerases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Silvian, L F -- Wang, J -- Steitz, T A -- GM22778/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1999 Aug 13;285(5430):1074-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics, Yale University, and Howard Hughes Medical Institute, New Haven, CT 06520-8114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10446055" target="_blank"〉PubMed〈/a〉
    Keywords: Acylation ; Adenosine Monophosphate/analogs & derivatives/metabolism ; Amino Acids/metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA-Directed DNA Polymerase/metabolism ; Glutamate-tRNA Ligase/chemistry/metabolism ; Isoleucine/metabolism ; Isoleucine-tRNA Ligase/*chemistry/*metabolism ; Models, Molecular ; Mupirocin/chemistry/*metabolism ; Nucleic Acid Conformation ; Oligopeptides/metabolism ; Protein Conformation ; Protein Structure, Secondary ; RNA, Transfer, Gln/chemistry/metabolism ; RNA, Transfer, Ile/*chemistry/*metabolism ; Staphylococcus aureus/enzymology ; Substrate Specificity
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  • 88
    Publication Date: 1999-02-19
    Description: Microdeletions of chromosome 22q11 are the most common genetic defects associated with cardiac and craniofacial anomalies in humans. A screen for mouse genes dependent on dHAND, a transcription factor implicated in neural crest development, identified Ufd1, which maps to human 22q11 and encodes a protein involved in degradation of ubiquitinated proteins. Mouse Ufd1 was specifically expressed in most tissues affected in patients with 22q11 deletion syndrome. The human UFD1L gene was deleted in all 182 patients studied with 22q11 deletion, and a smaller deletion of approximately 20 kilobases that removed exons 1 to 3 of UFD1L was found in one individual with features typical of 22q11 deletion syndrome. These data suggest that UFD1L haploinsufficiency contributes to the congenital heart and craniofacial defects seen in 22q11 deletion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamagishi, H -- Garg, V -- Matsuoka, R -- Thomas, T -- Srivastava, D -- R01HL57181-01/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1999 Feb 19;283(5405):1158-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Division of Cardiology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Room NA8.124, Dallas, TX 75235-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10024240" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta, Thoracic/abnormalities/embryology/metabolism ; Basic Helix-Loop-Helix Transcription Factors ; Cell Cycle Proteins/genetics ; Chromosomes, Human, Pair 22/*genetics ; Craniofacial Abnormalities/*genetics ; DNA-Binding Proteins/genetics/physiology ; Embryo, Mammalian/metabolism ; *Gene Deletion ; Gene Expression Regulation, Developmental ; Heart/embryology ; Heart Defects, Congenital/*genetics ; Humans ; Mice ; Neural Crest/cytology/embryology ; Phenotype ; Proteins/*genetics/physiology ; Transcription Factors/genetics/physiology ; Ubiquitins/metabolism ; Zebrafish Proteins
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-07-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hemminki, E -- Hailey, D -- Koivusalo, M -- New York, N.Y. -- Science. 1999 Jul 9;285(5425):203-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Research and Development Centre for Welfare and Health, Helsinki, Finland. elina.hemminki@stakes.fi〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10428717" target="_blank"〉PubMed〈/a〉
    Keywords: Anticholesteremic Agents/therapeutic use ; Canada ; Commerce ; Contraceptive Agents, Female ; Drug Approval ; Finland ; International Cooperation ; Jurisprudence ; Levonorgestrel ; Publishing ; Technology Assessment, Biomedical/*legislation & jurisprudence ; United States
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  • 90
    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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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-09-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmuth, L -- New York, N.Y. -- Science. 1999 Aug 20;285(5431):1190-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10484726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Estradiol/*pharmacology/toxicity ; *Genetic Variation ; Humans ; Litter Size ; Male ; Maximum Allowable Concentration ; Mice ; Mice, Inbred Strains ; Species Specificity ; Spermatogenesis/*drug effects ; Testis/*drug effects ; *Toxicity Tests
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  • 92
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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〉Hen, R -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2068-9; author reply 2069-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523202" target="_blank"〉PubMed〈/a〉
    Keywords: *Alcohol Drinking ; Animals ; Crosses, Genetic ; *Gene Frequency ; Mice ; Mice, Knockout/*genetics ; Receptor, Serotonin, 5-HT1B ; Receptors, Serotonin/genetics/*physiology ; Stem Cells
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-02-26
    Description: Biological weapons have recently attracted the attention and the resources of the nation. Discerning the nature of the threat of bioweapons as well as appropriate responses to them requires greater attention to the biological characteristics of these instruments of war and terror. The dominant paradigm of a weapon as a nuclear device that explodes or a chemical cloud that is set adrift leaves us ill-equipped conceptually and practically to assess and thus to prevent the potentially devastating effects of bioterrorism. Strengthening the public health and infectious disease infrastructure is an effective step toward averting the suffering that could be wrought by a terrorist's use of a biological agent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henderson, D A -- New York, N.Y. -- Science. 1999 Feb 26;283(5406):1279-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins Center for Civilian Biodefense Studies, Johns Hopkins School of Public Health, Suite 850, Candler Building, 111 Market Place, Baltimore, MD 21202, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10037590" target="_blank"〉PubMed〈/a〉
    Keywords: Anthrax/epidemiology/prevention & control/therapy/transmission ; *Biological Warfare/prevention & control ; Disaster Planning ; Disease Outbreaks ; Humans ; *Public Health ; Smallpox/epidemiology/prevention & control/therapy/transmission ; United States ; Vaccination ; *Violence/prevention & control
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, M -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):660-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10577216" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/chemistry/physiology ; Dendritic Cells, Follicular/chemistry/physiology ; Gene Targeting ; Genetic Predisposition to Disease ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Neurons/chemistry ; Prion Diseases/*etiology/genetics/therapy ; Prions/genetics/metabolism/*pathogenicity
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lipman, N S -- Nguyen, H -- Perkins, S -- New York, N.Y. -- Science. 1999 May 14;284(5417):1123.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10366341" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Laboratory/virology ; Blood/*virology ; China ; *Ectromelia virus ; Ectromelia, Infectious/epidemiology/*transmission ; Mice/*virology ; Rodent Diseases/epidemiology/*transmission ; United States
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  • 96
    Publication Date: 1999
    Description: Stable delivery of a therapeutic protein under pharmacologic control was achieved through in vivo somatic gene transfer. This system was based on the expression of two chimeric, human-derived proteins that were reconstituted by rapamycin into a transcription factor complex. A mixture of two adeno-associated virus vectors, one expressing the transcription factor chimeras and one containing erythropoietin (Epo) under the control of a promoter responsive to the transcription factor, was injected into skeletal muscle of immune-competent mice. Administration of rapamycin resulted in 200-fold induction of plasma Epo. Stable engraftment of this humanized system in immune-competent mice was achieved for 6 months with similar results for at least 3 months in a rhesus monkey.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ye, X -- Rivera, V M -- Zoltick, P -- Cerasoli, F Jr -- Schnell, M A -- Gao, G -- Hughes, J V -- Gilman, M -- Wilson, J M -- P01 AR/NS43648-03/AR/NIAMS NIH HHS/ -- P30 DK47757-05/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):88-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9872748" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytomegalovirus/genetics ; Dependovirus/genetics ; Erythropoietin/administration & dosage/blood/*genetics ; Female ; Gene Expression Regulation ; *Gene Transfer Techniques ; Genetic Therapy/*methods ; Genetic Vectors ; Hematocrit ; Injections, Intramuscular ; Macaca mulatta ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Muscle, Skeletal ; Promoter Regions, Genetic ; Recombinant Fusion Proteins ; Recombinant Proteins ; Sirolimus/*pharmacology ; Transcription Factors/*genetics
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  • 97
    Publication Date: 1999-12-03
    Description: Linker proteins function as molecular scaffolds to localize enzymes with substrates. In B cells, B cell linker protein (BLNK) links the B cell receptor (BCR)-activated Syk kinase to the phosphoinositide and mitogen-activated kinase pathways. To examine the in vivo role of BLNK, mice deficient in BLNK were generated. B cell development in BLNK-/- mice was blocked at the transition from B220+CD43+ progenitor B to B220+CD43- precursor B cells. Only a small percentage of immunoglobulin M++ (IgM++), but not mature IgMloIgDhi, B cells were detected in the periphery. Hence, BLNK is an essential component of BCR signaling pathways and is required to promote B cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pappu, R -- Cheng, A M -- Li, B -- Gong, Q -- Chiu, C -- Griffin, N -- White, M -- Sleckman, B P -- Chan, A C -- AI42787/AI/NIAID NIH HHS/ -- CA71516/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1999 Dec 3;286(5446):1949-54.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Division of Rheumatology, Department of Medicine, Howard Hughes Medical Institute, 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/10583957" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Aging ; Animals ; B-Lymphocyte Subsets/cytology/immunology ; B-Lymphocytes/*cytology/immunology/*metabolism ; Bone Marrow Cells/cytology/immunology ; Carrier Proteins/genetics/*physiology ; Cell Count ; Cell Differentiation ; Cell Separation ; Cell Size ; Flow Cytometry ; Gene Targeting ; Hematopoietic Stem Cells/*cytology/metabolism ; Immunoglobulin M/analysis ; Leukopoiesis ; Lymphoid Tissue/cytology/immunology ; Mice ; Mice, Inbred C57BL ; *Phosphoproteins ; Receptors, Antigen, B-Cell/*metabolism ; Second Messenger Systems ; Signal Transduction
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  • 98
    Publication Date: 1999-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pardes, H -- Manton, K G -- Lander, E S -- Tolley, H D -- Ullian, A D -- Palmer, H -- New York, N.Y. -- Science. 1999 Jan 1;283(5398):36-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. hp2@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9917262" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; *Biotechnology/economics ; *Delivery of Health Care ; Disabled Persons ; Drug Industry ; *Economics, Medical ; *Health Care Costs ; Health Status ; Humans ; Longevity ; *Research ; United States
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  • 99
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, M -- New York, N.Y. -- Science. 1999 May 28;284(5419):1453, 1455.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10383320" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry ; Animals ; Carcinogens/*analysis ; Cattle ; Drug Residues/adverse effects/*analysis ; Estradiol/adverse effects/*analysis ; European Union ; *Food Contamination ; Gonadal Steroid Hormones/adverse effects/*analysis ; Humans ; Meat/adverse effects/*analysis ; Mutagens/analysis ; Neoplasms/chemically induced ; United States ; United States Food and Drug Administration
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  • 100
    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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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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