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  • Base Sequence
  • Female
  • Models, Molecular
  • 1990-1994  (294)
  • 1993  (294)
  • 1
    Publication Date: 1993-03-05
    Description: Fertilization depends on cell surface recognition proteins that interact and thereby mediate binding and subsequent fusion of the sperm and egg. Overlapping complementary DNA's encoding the egg plasma membrane receptor for sperm from the sea urchin Strongylocentrotus purpuratus were cloned and sequenced. Analysis of the deduced primary structure suggests that the receptor is a transmembrane protein with a short cytoplasmic domain. This domain showed no sequence similarity to known protein sequences. In contrast, the extracellular, sperm binding domain of the receptor did show sequence similarity to the heat shock protein 70 (hsp70) family of proteins. Recombinant protein representing this portion of the receptor bound to the sperm protein, binding, and also inhibited fertilization in a species-specific manner; beads coated with the protein became specifically bound to acrosome-reacted sperm. These data provide a basis for detailed investigations of molecular interactions that occur in gamete recognition and egg activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Foltz, K R -- Partin, J S -- Lennarz, W J -- HD18590/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1993 Mar 5;259(5100):1421-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, University of California, Santa Barbara 93106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8383878" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cloning, Molecular ; Female ; Fertilization ; Heat-Shock Proteins/*genetics ; Humans ; Male ; Molecular Sequence Data ; Ovum/physiology ; Receptors, Cell Surface/*genetics/metabolism ; Recombinant Proteins/metabolism ; Restriction Mapping ; Sea Urchins ; Sequence Homology, Amino Acid ; Sperm-Ovum Interactions ; Spermatozoa/cytology/physiology
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, J -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1712-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8390093" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/therapeutic use ; *Acquired Immunodeficiency Syndrome/drug therapy/immunology/prevention & control ; Drug Therapy, Combination ; Female ; Humans ; Immunity, Cellular ; Male ; Sexually Transmitted Diseases/prevention & control ; Zalcitabine/therapeutic use ; Zidovudine/therapeutic use
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barash, D P -- New York, N.Y. -- Science. 1993 Oct 22;262(5133):491.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211168" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Child ; Child Abuse ; Female ; Humans ; Male ; *Sexual Behavior ; Sexual Behavior, Animal ; Sociology ; *Violence
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-08
    Description: Oncogenes discovered in retroviruses such as Rous sarcoma virus were generated by transduction of cellular proto-oncogenes into the viral genome. Several different kinds of junctions between the viral and proto-oncogene sequences have been found in different viruses. A system of retrovirus vectors and a protocol that mimicked this transduction during a single cycle of retrovirus replication was developed. The transduction involved the formation of a chimeric viral-cellular RNA, strand switching of the reverse transcription growing point from an infectious retrovirus to the chimeric RNA, and often a subsequent deletion during the rest of viral DNA synthesis. A short region of sequence identity was frequently used for the strand switching. The rate of this process was about 0.1 to 1 percent of the rate of homologous retroviral recombination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, J -- Temin, H M -- CA-07175/CA/NCI NIH HHS/ -- CA-22443/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 8;259(5092):234-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8421784" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Cinnamates ; *DNA Replication ; DNA, Viral/chemistry/genetics ; Drug Resistance/genetics ; Genes, Viral ; Genetic Vectors ; Hygromycin B/analogs & derivatives ; Kinetics ; Mice ; Molecular Sequence Data ; Moloney murine leukemia virus/genetics ; Neomycin ; Plasmids ; *Proto-Oncogenes ; RNA, Viral/analysis/genetics ; *Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Retroviridae/*genetics/physiology ; Transfection ; *Virus Replication
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  • 5
    Publication Date: 1993-10-22
    Description: Glycogen storage disease (GSD) type 1a is caused by the deficiency of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lei, K J -- Shelly, L L -- Pan, C J -- Sidbury, J B -- Chou, J Y -- New York, N.Y. -- Science. 1993 Oct 22;262(5133):580-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211187" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; DNA, Complementary/genetics ; Exons ; Glucose-6-Phosphatase/*genetics/metabolism ; Glycogen Storage Disease Type I/enzymology/*genetics ; Glycosylation ; Humans ; Liver/enzymology ; Mice ; Molecular Sequence Data ; *Mutation ; Protein Conformation ; Transfection
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  • 6
    Publication Date: 1993-08-27
    Description: The gene encoding alpha 6(IV) collagen, COL4A6, was identified on the human X chromosome in a head-to-head arrangement and within 452 base pairs of the alpha 5(IV) collagen gene, COL4A5. In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes. In some families, AS cosegregates with diffuse leiomyomatosis (DL), a benign smooth muscle tumor diathesis. Here it is shown that patients with AS-DL harbor deletions that disrupt both COL4A5 and COL4A6. Thus, type IV collagen may regulate smooth muscle differentiation and morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, J -- Mochizuki, T -- Smeets, H -- Antignac, C -- Laurila, P -- de Paepe, A -- Tryggvason, K -- Reeders, S T -- New York, N.Y. -- Science. 1993 Aug 27;261(5125):1167-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536-0812.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8356449" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Differentiation ; Collagen/chemistry/*genetics ; Exons ; Female ; Fetus/metabolism ; *Gene Deletion ; Genetic Linkage ; Humans ; Leiomyoma/*genetics ; Male ; Molecular Sequence Data ; Morphogenesis ; Muscle, Smooth/cytology ; Mutation ; Nephritis, Hereditary/*genetics ; RNA, Messenger/genetics/metabolism
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  • 7
    Publication Date: 1993-11-05
    Description: Hydrogen exchange pulse labeling and stopped-flow circular dichroism were used to establish that the structure of the earliest detectable intermediate formed during refolding of apomyoglobin corresponds closely to that of a previously characterized equilibrium molten globule. This compact, cooperatively folded intermediate was formed in less than 5 milliseconds and contained stable, hydrogen-bonded secondary structure localized in the A, G, and H helices and part of the B helix. The remainder of the B helix folded on a much slower time scale, followed by the C and E helices and the CD loop. The data indicate that a molten globule intermediate was formed on the kinetic folding pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jennings, P A -- Wright, P E -- DK-34909/DK/NIDDK NIH HHS/ -- GM14541/GM/NIGMS NIH HHS/ -- RR04953/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 5;262(5135):892-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235610" target="_blank"〉PubMed〈/a〉
    Keywords: Apoproteins/*chemistry ; Circular Dichroism ; Hydrogen/chemistry ; Hydrogen Bonding ; Kinetics ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Myoglobin/*chemistry ; *Protein Conformation ; *Protein Folding ; Protein Structure, Secondary
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lippman, M E -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):631-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430312" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Factors/*therapeutic use ; Breast Neoplasms/*therapy ; Female ; Growth Substances/*therapeutic use ; Humans ; Prognosis
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  • 9
    Publication Date: 1993-08-06
    Description: The structure of the bifunctional, pyridoxal phosphate-dependent enzyme dialkylglycine decarboxylase was determined to 2.1-angstrom resolution. Model building suggests that a single cleavage site catalyzes both decarboxylation and transamination by maximizing stereoelectronic advantages and providing electrostatic and general base catalysis. The enzyme contains two binding sites for alkali metal ions. One is located near the active site and accounts for the dependence of activity on potassium ions. The other is located at the carboxyl terminus of an alpha helix. These sites help show how proteins can specifically bind alkali metals and how these ions can exert functional effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toney, M D -- Hohenester, E -- Cowan, S W -- Jansonius, J N -- GM13854/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):756-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, University of Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8342040" target="_blank"〉PubMed〈/a〉
    Keywords: Amination ; Amino Acid Sequence ; Binding Sites ; Carboxy-Lyases/*chemistry/metabolism ; Catalysis ; Computer Graphics ; Decarboxylation ; Metals, Alkali/*metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Structure, Secondary ; X-Ray Diffraction
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  • 10
    Publication Date: 1993-02-26
    Description: Interferon inhibits expression of human immunodeficiency virus type-1 (HIV-1) through unknown mechanisms. A gene inducible by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma) was isolated by screening of a human complementary DNA library for proteins binding to the Rev-responsive element (RRE) of HIV-1. The product of this gene, RBP9-27, was shown to bind RNA in vitro and to inhibit HIV-1 expression after transfection into human cells. RBP9-27 primarily inhibited Rev-dependent posttranscriptional steps of viral gene expression. Thus, RBP9-27 is a cellular factor that antagonizes Rev function. These results suggest an interferon-induced antiviral mechanism operating through the induction of RNA binding proteins such as RBP9-27. Elucidation of RBP9-27 function may lead to a better understanding of the mechanism of interferon action during HIV-1 infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Constantoulakis, P -- Campbell, M -- Felber, B K -- Nasioulas, G -- Afonina, E -- Pavlakis, G N -- N0-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 26;259(5099):1314-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Retrovirus Section, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7680491" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; *Gene Expression Regulation, Viral ; Genes, env ; *Genes, rev ; HIV-1/*genetics ; Humans ; Interferons/pharmacology ; *Membrane Proteins ; Molecular Sequence Data ; Oligodeoxyribonucleotides/chemistry ; RNA-Binding Proteins/*genetics ; Regulatory Sequences, Nucleic Acid
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  • 11
    Publication Date: 1993-09-17
    Description: The bcl-2 proto-oncogene can prevent the death of many cell types. Mice were generated that were chimeric for the homozygous inactivation of bcl-2. Lymphocytes without Bcl-2 differentiated into phenotypically mature cells. However, in vitro, the mature T cells that lacked Bcl-2 had shorter life-spans and increased sensitivity to glucocorticoids and gamma-irradiation. In contrast, stimulation of CD3 inhibited the death of these cells. T and B cells with no Bcl-2 disappeared from the bone marrow, thymus, and periphery by 4 weeks of age. Thus, Bcl-2 was dispensable for lymphocyte maturation, but was required for a stable immune system after birth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakayama, K -- Negishi, I -- Kuida, K -- Shinkai, Y -- Louie, M C -- Fields, L E -- Lucas, P J -- Stewart, V -- Alt, F W -- AI 15322/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 17;261(5128):1584-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8372353" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD3/immunology ; Apoptosis ; B-Lymphocytes/cytology/*immunology ; Base Sequence ; Bone Marrow/immunology ; Bone Marrow Cells ; Cell Line ; Chimera ; Homozygote ; Humans ; Lymphoid Tissue/cytology/immunology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Proto-Oncogene Proteins/genetics/*physiology ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogenes ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/cytology/*immunology
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  • 12
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-07
    Description: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q. Differences between tumor and normal DNA were detected in 25 of the 90 (28 percent) tumors examined. This instability appeared as either a substantial change in repeat length (often heterogeneous in nature) or a minor change (typically two base pairs). Microsatellite instability was significantly correlated with the tumor's location in the proximal colon (P = 0.003), with increased patient survival (P = 0.02), and, inversely, with loss of heterozygosity for chromosomes 5q, 17p, and 18q. These data suggest that some colorectal cancers may arise through a mechanism that does not necessarily involve loss of heterozygosity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thibodeau, S N -- Bren, G -- Schaid, D -- CA-15083-18E8.1/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 May 7;260(5109):816-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics Laboratory, Mayo Clinic, Rochester, MN 55905.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8484122" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 5 ; Colonic Neoplasms/*genetics ; Colorectal Neoplasms/*genetics ; DNA, Neoplasm/*genetics ; DNA, Satellite/*genetics ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; *Mutation ; Polymerase Chain Reaction ; Repetitive Sequences, Nucleic Acid
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-14
    Description: Guanosine triphosphate-binding regulatory proteins (G proteins) are key elements in transmembrane signaling and have been implicated as regulators of more complex biological processes such as differentiation and development. The G protein G alpha i2 is capable of mediating the inhibitory control of adenylylcyclase and regulates stem cell differentiation to primitive endoderm. Here an antisense RNA to G alpha i2 was expressed in a hybrid RNA construct whose expression was both tissue-specific and induced at birth. Transgenic mice in which the antisense construct was expressed displayed a lack of normal development in targeted organs that correlated with the absence of G alpha i2. The loss of G alpha i2 expression in adipose tissue of the transgenic mice was correlated with a rise in basal levels of adenosine 3',5'-monophosphate (cAMP) and the loss of receptor-mediated inhibition of adenylylcyclase. These data expand our understanding of G protein function in vivo and demonstrate the necessity for G alpha i2 in the development of liver and fat.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moxham, C M -- Hod, Y -- Malbon, C C -- New York, N.Y. -- Science. 1993 May 14;260(5110):991-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pharmacology, State University of New York (SUNY)/Stony Brook 11794-8651.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493537" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*growth & development/metabolism ; Animals ; Animals, Newborn/growth & development ; Base Sequence ; Body Weight ; GTP-Binding Proteins/biosynthesis/genetics/*physiology ; Growth/drug effects/*physiology ; Kidney/growth & development/metabolism ; Liver/*growth & development/metabolism ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Phosphoenolpyruvate Carboxykinase (GTP)/genetics ; RNA, Antisense/*genetics ; Transfection
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  • 14
    Publication Date: 1993-10-01
    Description: Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copeland, N G -- Jenkins, N A -- Gilbert, D J -- Eppig, J T -- Maltais, L J -- Miller, J C -- Dietrich, W F -- Weaver, A -- Lincoln, S E -- Steen, R G -- HG00198/HG/NHGRI NIH HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 1;262(5130):57-66.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211130" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Chromosome Mapping ; Cloning, Molecular ; Crosses, Genetic ; Female ; Genetic Markers ; *Genome ; Human Genome Project ; Humans ; Male ; Mice/*genetics ; Multigene Family ; Muridae/*genetics ; Mutation ; Neoplasms/genetics
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-12
    Description: Upon activation, B lymphocytes can change the class of the antibody they express by immunoglobulin class switch recombination. Cytokines can direct this recombination to distinct classes by the specific activation of repetitive recombinogenic DNA sequences, the switch regions. Recombination to a particular switch region (s gamma 1) was abolished in mice that were altered to lack sequences that are 5' to the s gamma 1 region. This result directly implicates the functional importance of 5' switch region flanking sequences in the control of class switch recombination. Mutant mice exhibit a selective agammaglobulinemia and may be useful in the assessment of the biological importance of immunoglobulin G1.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jung, S -- Rajewsky, K -- Radbruch, A -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):984-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genetics, University of Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8438159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*immunology ; Base Sequence ; Cell Line ; Chimera ; Drug Resistance/genetics ; Embryo, Mammalian ; *Gene Deletion ; Immunoglobulin G/genetics ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Switch Region/*genetics ; Interleukin-4/pharmacology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutagenesis ; Neomycin ; *Recombination, Genetic ; Stem Cells
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  • 16
    Publication Date: 1993-11-05
    Description: B7 delivers a costimulatory signal through CD28, resulting in interleukin-2 secretion and T cell proliferation. Blockade of this pathway results in T cell anergy. The in vivo role of B7 was evaluated with B7-deficient mice. These mice had a 70 percent decrease in costimulation of the response to alloantigen. Despite lacking B7 expression, activated B cells from these mice bound CTLA-4 and GL1 monoclonal antibody, demonstrating that alternative CTLA-4 ligand or ligands exist. These receptors are functionally important because the residual allogenic mixed lymphocyte responses were blocked by CTLA4Ig. Characterization of these CTLA-4 ligands should lead to strategies for manipulating the immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freeman, G J -- Borriello, F -- Hodes, R J -- Reiser, H -- Hathcock, K S -- Laszlo, G -- McKnight, A J -- Kim, J -- Du, L -- Lombard, D B -- CA 40216/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 5;262(5135):907-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7694362" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antigens, CD ; Antigens, CD80/genetics/*immunology/metabolism ; Antigens, Differentiation/immunology/*metabolism ; B-Lymphocytes/*immunology ; Base Sequence ; CTLA-4 Antigen ; Cell Line ; *Immunoconjugates ; Interleukin-2/secretion ; Isoantigens/immunology ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; T-Lymphocytes/*immunology ; Transfection
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  • 17
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-09-10
    Description: An iterative in vitro selection procedure was used to isolate a new class of catalytic RNAs (ribozymes) from a large pool of random-sequence RNA molecules. These ribozymes ligate two RNA molecules that are aligned on a template by catalyzing the attack of a 3'-hydroxyl on an adjacent 5'-triphosphate--a reaction similar to that employed by the familiar protein enzymes that synthesize RNA. The corresponding uncatalyzed reaction also yields a 3',5'-phosphodiester bond. In vitro evolution of the population of new ribozymes led to improvement of the average ligation activity and the emergence of ribozymes with reaction rates 7 million times faster than the uncatalyzed reaction rate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bartel, D P -- Szostak, J W -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1411-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7690155" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Biological Evolution ; Catalysis ; Kinetics ; Magnesium/metabolism ; Molecular Sequence Data ; Mutation ; Oligoribonucleotides/metabolism ; RNA/*metabolism ; RNA Ligase (ATP)/chemistry/isolation & purification/metabolism ; RNA, Catalytic/chemistry/*isolation & purification/metabolism ; Temperature ; Templates, Genetic
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  • 18
    Publication Date: 1993-06-25
    Description: CD4+ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaudi infection. TH1 cells protect by a nitric oxide-dependent mechanism, whereas TH2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor-Robinson, A W -- Phillips, R S -- Severn, A -- Moncada, S -- Liew, F Y -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1993 Jun 25;260(5116):1931-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Laboratories for Experimental Parasitology, University of Glasgow, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8100366" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Protozoan/biosynthesis ; Arginine/analogs & derivatives/pharmacology ; CD4-Positive T-Lymphocytes/*immunology ; Cell Line ; Female ; Immunoglobulin G/*biosynthesis ; Lymphocyte Depletion ; Malaria/*immunology ; Mice ; Mice, Inbred Strains ; Nitrates/blood ; Nitric Oxide/*metabolism ; Plasmodium chabaudi/*immunology ; T-Lymphocyte Subsets/*immunology ; omega-N-Methylarginine
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freedman, D -- New York, N.Y. -- Science. 1993 Aug 13;261(5123):844-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8346437" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Artificial Intelligence ; Base Sequence ; Collagen/chemistry/genetics/physiology ; DNA/chemistry/genetics ; Humans ; Molecular Sequence Data ; Mutation ; *Protein Structure, Secondary ; *Protein Structure, Tertiary ; *Sequence Analysis, DNA ; Software
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-03
    Description: Studies in vivo and in vitro have shown that the packaging of DNA into chromatin can affect gene expression. Here, binding of the yeast transcriptional activator GAL4 to DNA in chromatin has been investigated in vivo with a yeast episome. A positioned nucleosome that is present in cells grown in glucose and contains a single GAL4 binding site is disrupted by GAL4 binding in galactose. GAL4 can also bind to DNA in chromatin when the carboxyl-terminal activation domain of GAL4 is either masked by GAL80 or is absent. These results show that a transcription factor can bind to its site in vivo in what would appear to be a repressive chromatin structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morse, R H -- New York, N.Y. -- Science. 1993 Dec 3;262(5139):1563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8248805" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; DNA-Binding Proteins/*metabolism ; Fungal Proteins/*metabolism ; Galactose/metabolism ; Glucose/metabolism ; Molecular Sequence Data ; Nucleosomes/*metabolism ; Plasmids ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/*metabolism ; *Saccharomyces cerevisiae Proteins ; Transcription Factors/*metabolism
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  • 21
    Publication Date: 1993-11-12
    Description: Rapid photoinduced electron transfer is demonstrated over a distance of greater than 40 angstroms between metallointercalators that are tethered to the 5' termini of a 15-base pair DNA duplex. An oligomeric assembly was synthesized in which the donor is Ru(phen)2dppz2+ (phen, phenanthroline, and dppz, dipyridophenazine) and the acceptor is Rh(phi)2phen3+ (phi, phenanthrenequinone diimine). These metal complexes are intercalated either one or two base steps in from the helix termini. Although the ruthenium-modified oligonucleotide hybridized to an unmodified complement luminesces intensely, the ruthenium-modified oligomer hybridized to the rhodium-modified oligomer shows no detectable luminescence. Time-resolved studies point to a lower limit of 10(9) per second for the quenching rate. No quenching was observed upon metallation of two complementary octamers by Ru(phen)3(2+) and Rh(phen)3(3+) under conditions where the phen complexes do not intercalate. The stacked aromatic heterocycles of the DNA duplex therefore serve as an efficient medium for coupling electron donors and acceptors over very long distances.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murphy, C J -- Arkin, M R -- Jenkins, Y -- Ghatlia, N D -- Bossmann, S H -- Turro, N J -- Barton, J K -- GM49216/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 12;262(5136):1025-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Beckman Institute, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7802858" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA/*chemistry ; *Electrons ; Intercalating Agents/*chemistry ; Lasers ; Luminescence ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/*chemistry ; Organometallic Compounds/chemistry ; Phenanthrenes/chemistry ; Phenanthrolines/chemistry ; Photochemistry
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  • 22
    Publication Date: 1993-07-30
    Description: Anopheles gambiae, the primary vector of human malaria in Africa, is responsible for approximately a million deaths per year, mostly of children. Despite its significance in disease transmission, this mosquito has not been studied extensively by genetic or molecular techniques. To facilitate studies on this vector, a genetic map has been developed that covers the X chromosome at an average resolution of 2 centimorgans. This map has been integrated with the chromosome banding pattern and used to localize a recessive, sex-linked mutation (white eye) to within 1 centimorgan of flanking markers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, L -- Collins, F H -- Kumar, V -- Kafatos, F C -- New York, N.Y. -- Science. 1993 Jul 30;261(5121):605-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8342025" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Anopheles/*genetics ; Base Sequence ; Chromosome Banding ; *Chromosome Mapping ; Crosses, Genetic ; DNA, Satellite/genetics ; Female ; *Genes, Insect ; Genes, Recessive ; Genetic Markers ; Insect Vectors/*genetics ; Malaria/transmission ; Male ; Molecular Sequence Data ; Mutation ; Recombination, Genetic ; *X Chromosome
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  • 23
    Publication Date: 1993-05-21
    Description: The cytotoxicity of human natural killer (NK) cells is modulated by the major histocompatibility complex human leukocyte antigen (HLA)-C molecules on the surface of the target cell. Alloreactive NK cells specific for the NK-1 alloantigen could be reproducibly generated from individuals that were homozygous for HLA-C with asparagine at residue 77 and lysine at residue 80 [HLA-C(Asn77,Lys80)] by stimulation with target cells that were homozygous for HLA-C(Ser77,Asn80); the reciprocal stimulation yielded NK cells specific for the NK-2 alloantigen. However, neither homozygous target cell stimulated the generation of alloreactive NK cells from heterozygous individuals. Thus, these data reveal an unanticipated difference between human NK alloreactivity defined by this system and murine "hybrid resistance."〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Colonna, M -- Brooks, E G -- Falco, M -- Ferrara, G B -- Strominger, J L -- CA 47554/CA/NCI NIH HHS/ -- KO8 AI01064/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 May 21;260(5111):1121-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunogenetics, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493555" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Cell Line ; *Cytotoxicity, Immunologic ; Genotype ; HLA-C Antigens/genetics/*immunology ; Heterozygote ; Homozygote ; Humans ; Isoantigens/*immunology ; Killer Cells, Natural/*immunology ; Mice ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Polymorphism, Genetic
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-09
    Description: Direct gene transfer into adult animals resulting in generalized or tissue-specific expression would facilitate rapid analysis of transgene effects and allow precise in vivo manipulation of biologic processes at the molecular level. A single intravenous injection of expression plasmid:cationic liposome complexes into adult mice efficiently transfected virtually all tissues. In addition to vascular endothelial cells, most of the extravascular parenchymal cells present in many tissues including the lung, spleen, lymph nodes, and bone marrow expressed the transgene without any apparent treatment-related toxicity. The transgene was still expressed in large numbers of cells in multiple tissues for at least 9 weeks after a single injection. Expression could be targeted to specific tissues and cell types, depending on the promoter element used.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, N -- Liggitt, D -- Liu, Y -- Debs, R -- New York, N.Y. -- Science. 1993 Jul 9;261(5118):209-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Institute, University of California, San Francisco 94143-0128.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7687073" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Bone Marrow/metabolism ; Chloramphenicol O-Acetyltransferase/genetics ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; Cytomegalovirus/genetics ; Female ; *Gene Expression ; Injections, Intravenous ; Liposomes ; Liver/metabolism ; Lung/metabolism ; Lung Neoplasms/genetics ; Lymphoid Tissue/metabolism ; Membrane Proteins/genetics ; Mice ; Mice, Inbred ICR ; Mice, Transgenic ; Molecular Sequence Data ; Myocardium/metabolism ; Oligodeoxyribonucleotides ; Phosphatidylethanolamines/chemistry ; Plasmids ; Quaternary Ammonium Compounds ; *Transfection
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  • 25
    Publication Date: 1993-10-15
    Description: In cystic fibrosis (CF), absence or dysfunction of a phosphorylation-regulated chloride channel [CF transmembrane conductance regulator (CFTR)] leads to the loss or reduction of chloride secretion into the airways. Active sodium absorption is also increased in CF, and both of these ion transport changes could alter fluid transport across the airways. Under baseline conditions, cultured human airway epithelia from normal individuals absorbed fluid, and this absorption was increased in epithelia from patients with CF. In normal and CF epithelial cultures fluid absorption was inhibited by amiloride. Adenosine 3',5'-monophosphate stimulated fluid secretion in normal epithelial cultures but not in cultures from individuals with CF. In contrast, fluid secretion induced by nucleotide triphosphates (uridine triphosphate or adenosine triphosphate) was unaltered in cultures of epithelia from patients with CF, suggesting an approach to the treatment of CF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, C -- Finkbeiner, W E -- Widdicombe, J H -- McCray, P B Jr -- Miller, S S -- HL 42368/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):424-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211164" target="_blank"〉PubMed〈/a〉
    Keywords: Absorption ; Adenosine Triphosphate/pharmacology ; Adolescent ; Adult ; Amiloride/pharmacology ; Body Fluids/*metabolism ; Cells, Cultured ; Cyclic AMP/pharmacology ; Cystic Fibrosis/*metabolism ; Epithelial Cells ; Epithelium/metabolism ; Female ; Humans ; Male ; Middle Aged ; Nasal Mucosa/cytology/*metabolism ; Sodium/metabolism ; Sodium Channels/metabolism ; Trachea/cytology/*metabolism ; Uridine Triphosphate/pharmacology
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Funder, J W -- New York, N.Y. -- Science. 1993 Feb 19;259(5098):1132-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baker Medical Research Institute, Prahran, Victoria, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8382375" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; DNA/*metabolism ; DNA-Binding Proteins/*metabolism ; Gene Expression Regulation ; Glucocorticoids/*physiology ; Mineralocorticoids/*physiology ; Models, Biological ; Molecular Sequence Data ; Receptors, Glucocorticoid/*metabolism ; Receptors, Mineralocorticoid ; Receptors, Steroid/*metabolism ; *Transcription, Genetic
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  • 27
    Publication Date: 1993-12-17
    Description: Intracellular recordings from simple cells of the cat visual cortex were used to test linear models for the generation of selectivity for the direction of visual motion. Direction selectivity has been thought to arise in part from nonlinear processes, as suggested by previous experiments that were based on extracellular recordings of action potentials. In intracellular recordings, however, the fluctuations in membrane potential evoked by moving stimuli were accurately predicted by the linear summation of responses to stationary stimuli. Nonlinear mechanisms were not required.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jagadeesh, B -- Wheat, H S -- Ferster, D -- R01 EY04726/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 17;262(5141):1901-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266083" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cats ; Female ; Mathematics ; Membrane Potentials ; *Motion Perception ; Neurons/physiology ; *Synaptic Transmission ; Visual Cortex/*physiology
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-08
    Description: The amino acid at position 160 of the ligand-binding subunit, alpha 1, is an important determinant of agonist and antagonist binding to the glycine receptor. Exchange of the neighboring residues, phenylalanine at position 159 and tyrosine at position 161, increased the efficacy of amino acid agonists. Whereas wild-type alpha 1 channels expressed in Xenopus oocytes required 0.7 millimolar beta-alanine for a half-maximal response, the doubly mutated (F159Y,Y161F) alpha 1 subunit had an affinity for beta-alanine (which was more potent than glycine) that was 110-fold that of the wild type. Also, gamma-aminobutyric acid and D-serine, amino acids that do not activate wild-type alpha 1 receptors, efficiently gated the mutant channel. Thus, aromatic hydroxyl groups are crucial for ligand discrimination at inhibitory amino acid receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmieden, V -- Kuhse, J -- Betz, H -- New York, N.Y. -- Science. 1993 Oct 8;262(5131):256-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurochemistry, Max Planck Institute for Brain Research, Frankfurt, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211147" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Female ; Glycine/metabolism ; Ion Channel Gating/drug effects ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oocytes ; Receptors, GABA/chemistry/metabolism ; Receptors, Glycine/chemistry/genetics/*metabolism ; Serine/pharmacology ; Taurine/pharmacology ; Xenopus ; beta-Alanine/*metabolism/pharmacology ; gamma-Aminobutyric Acid/*metabolism/pharmacology
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  • 29
    Publication Date: 1993-02-12
    Description: Biomolecular membranes display rich statistical mechanical behavior. They are classified as liquid in the absence of shear elasticity in the plane of the membrane and tethered (solid) when the neighboring molecules or subunits are connected and the membranes exhibit solid-like elastic behavior in the plane of the membrane. The spectrin skeleton of red blood cells was studied as a model tethered membrane. The static structure factor of the skeletons, measured by small-angle x-ray and light scattering, was fitted with a structure factor predicted with a model calculation. The model describes tethered membrane sheets with free edges in a flat phase, which is a locally rough but globally flat membrane configuration. The fit was good for large scattering vectors. The membrane roughness exponent, zeta, defined through h alpha L zeta, where h is the average amplitude of out-of-plane fluctuations and L is the linear membrane dimension, was determined to be 0.65 +/- 0.10. Computer simulations of model red blood cell skeletons also showed this flat phase. The value for the roughness exponent, which was determined from the scaling properties of membranes of different sizes, was consistent with that from the experiments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, C F -- Svoboda, K -- Lei, N -- Petsche, I B -- Berman, L E -- Safinya, C R -- Grest, G S -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):952-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8438153" target="_blank"〉PubMed〈/a〉
    Keywords: Chemistry, Physical ; Computer Simulation ; Electrochemistry ; Erythrocyte Membrane/chemistry/*ultrastructure ; Light ; Mathematics ; Models, Molecular ; Physicochemical Phenomena ; Scattering, Radiation ; Spectrin/chemistry/*ultrastructure ; X-Rays
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-04-16
    Description: Klenow fragment of Escherichia coli DNA polymerase I, which was cocrystallized with duplex DNA, positioned 11 base pairs of DNA in a groove that lies at right angles to the cleft that contains the polymerase active site and is adjacent to the 3' to 5' exonuclease domain. When the fragment bound DNA, a region previously referred to as the "disordered domain" became more ordered and moved along with two helices toward the 3' to 5' exonuclease domain to form the binding groove. A single-stranded, 3' extension of three nucleotides bound to the 3' to 5' exonuclease active site. Although this cocrystal structure appears to be an editing complex, it suggests that the primer strand approaches the catalytic site of the polymerase from the direction of the 3' to 5' exonuclease domain and that the duplex DNA product may bend to enter the cleft that contains the polymerase catalytic site.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beese, L S -- Derbyshire, V -- Steitz, T A -- GM28550/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 16;260(5106):352-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8469987" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Crystallization ; DNA/chemistry/*metabolism ; DNA Polymerase I/*chemistry/metabolism ; DNA Replication ; DNA, Single-Stranded/chemistry/metabolism ; Escherichia coli/*enzymology ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Templates, Genetic
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-12
    Description: The analysis of the differences between two complex genomes holds promise for the discovery of infectious agents and probes useful for genetic studies. A system was developed in which subtractive and kinetic enrichment was used to purify restriction endonuclease fragments present in one population of DNA fragments but not in another. Application of this method to DNA populations of reduced complexity ("representations") resulted in the isolation of probes to viral genomes present as single copies in human DNA, and probes that detect polymorphisms between two individuals. In principle, this system, called representational difference analysis (RDA), may also be used for isolating probes linked to sites of genomic rearrangements, whether occurring spontaneously and resulting in genetic disorders or cancer, or programmed during differentiation and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lisitsyn, N -- Wigler, M -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):946-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, NY 11724.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8438152" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae/genetics ; Bacteriophage lambda/genetics ; Base Sequence ; *Cloning, Molecular ; DNA/*chemistry ; DNA Probes ; DNA, Viral ; Female ; Gene Deletion ; Genetic Diseases, Inborn/genetics ; Humans ; Male ; Molecular Sequence Data ; Neoplasms/genetics ; Nucleic Acid Hybridization/methods ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Homology, Nucleic Acid
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  • 32
    Publication Date: 1993-08-20
    Description: The pericentric inversion of chromosome 16 [inv(16)(p13q22)] is a characteristic karyotypic abnormality associated with acute myeloid leukemia, most commonly of the M4Eo subtype. The 16p and 16q breakpoints were pinpointed by yeast artificial chromosome and cosmid cloning, and the two genes involved in this inversion were identified. On 16q the inversion occurred near the end of the coding region for CBF beta, also known as PEBP2 beta, a subunit of a heterodimeric transcription factor regulating genes expressed in T cells; on 16p a smooth muscle myosin heavy chain (SMMHC) gene (MYH11) was interrupted. In six of six inv(16) patient samples tested, an in-frame fusion messenger RNA was demonstrated that connected the first 165 amino acids of CBF beta with the tail region of SMMHC. The repeated coiled coil of SMMHC may result in dimerization of the CBF beta fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, P -- Tarle, S A -- Hajra, A -- Claxton, D F -- Marlton, P -- Freedman, M -- Siciliano, M J -- Collins, F S -- CA55164/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Aug 20;261(5124):1041-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8351518" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; *Chromosome Inversion ; *Chromosomes, Human, Pair 16 ; Cloning, Molecular ; Core Binding Factor Alpha 1 Subunit ; Core Binding Factor beta Subunit ; Core Binding Factors ; Cosmids ; DNA-Binding Proteins/*genetics ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myelomonocytic, Acute/*genetics ; Molecular Sequence Data ; Muscle, Smooth/chemistry ; Myosins/*genetics ; *Neoplasm Proteins ; Polymerase Chain Reaction ; Protein Multimerization ; Restriction Mapping ; Transcription Factor AP-2 ; Transcription Factors/*genetics
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-17
    Description: Here a method is described to identify genes encoding proteins that recognize a specific DNA sequence. A bank of random protein segments tagged with a transcriptional activation domain is screened for proteins that can activate a reporter gene containing the sequence in its promoter. This strategy was used to identify an essential protein that interacts in vivo with the yeast origin of DNA replication. Matches between its predicted amino acid sequence and peptide sequence obtained from the 50-kilodalton subunit of the yeast origin recognition complex (ORC) established that the gene isolated here, ORC6, encodes this subunit. These observations provide evidence that ORC recognizes yeast replication origins in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, J J -- Herskowitz, I -- AI18738/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 17;262(5141):1870-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266075" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Cycle ; *DNA Replication ; DNA, Fungal/metabolism ; DNA-Binding Proteins/chemistry/*genetics/metabolism ; Fungal Proteins/chemistry/*genetics/metabolism ; *Genes, Fungal ; Genes, Reporter ; Molecular Sequence Data ; Open Reading Frames ; Origin Recognition Complex ; Promoter Regions, Genetic ; *Replicon ; Repressor Proteins/chemistry/*genetics/metabolism ; Saccharomyces cerevisiae/cytology/*genetics/metabolism ; Saccharomyces cerevisiae Proteins
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  • 34
    Publication Date: 1993-11-05
    Description: A mysterious respiratory illness with high mortality was recently reported in the southwestern United States. Serologic studies implicated the hantaviruses, rodent-borne RNA viruses usually associated elsewhere in the world with hemorrhagic fever with renal syndrome. A genetic detection assay amplified hantavirus-specific DNA fragments from RNA extracted from the tissues of patients and deer mice (Peromyscus maniculatus) caught at or near patient residences. Nucleotide sequence analysis revealed the associated virus to be a new hantavirus and provided a direct genetic link between infection in patients and rodents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nichol, S T -- Spiropoulou, C F -- Morzunov, S -- Rollin, P E -- Ksiazek, T G -- Feldmann, H -- Sanchez, A -- Childs, J -- Zaki, S -- Peters, C J -- New York, N.Y. -- Science. 1993 Nov 5;262(5135):914-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235615" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Bunyaviridae Infections/epidemiology/*microbiology/veterinary ; DNA Primers ; *Disease Outbreaks ; *Disease Reservoirs ; *Genome, Viral ; Hantavirus/classification/*genetics/isolation & purification ; Humans ; Lung Diseases/epidemiology/*microbiology ; Molecular Sequence Data ; Peromyscus/*microbiology ; Phylogeny ; Polymerase Chain Reaction ; Rodent Diseases/epidemiology/microbiology ; Sequence Homology, Nucleic Acid ; Southwestern United States/epidemiology
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  • 35
    Publication Date: 1993-11-26
    Description: A DNA sequence rich in (A+T), located upstream of the -10, -35 region of the Escherichia coli ribosomal RNA promoter rrnB P1 and called the UP element, stimulates transcription by a factor of 30 in vivo, as well as in vitro in the absence of protein factors other than RNA polymerase (RNAP). When fused to other promoters, such as lacUV5, the UP element also stimulates transcription, indicating that it is a separate promoter module. Mutations in the carboxyl-terminal region of the alpha subunit of RNAP prevent stimulation of these promoters by the UP element although the mutant enzymes are effective in transcribing the "core" promoters (those lacking the UP element). Protection of UP element DNA by the mutant RNAPs is severely reduced in footprinting experiments, suggesting that the selective decrease in transcription might result from defective interactions between alpha and the UP element. Purified alpha binds specifically to the UP element, confirming that alpha acts directly in promoter recognition. Transcription of three other promoters was also reduced by the COOH-terminal alpha mutations. These results suggest that UP elements comprise a third promoter recognition region (in addition to the -10, -35 recognition hexamers, which interact with the sigma subunit) and may account for the presence of (A+T)-rich DNA upstream of many prokaryotic promoters. Since the same alpha mutations also block activation by some transcription factors, mechanisms of promoter stimulation by upstream DNA elements and positive control by certain transcription factors may be related.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ross, W -- Gosink, K K -- Salomon, J -- Igarashi, K -- Zou, C -- Ishihama, A -- Severinov, K -- Gourse, R L -- AI90035/AI/NIAID NIH HHS/ -- GM49242/GM/NIGMS NIH HHS/ -- R01 GM37048/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 26;262(5138):1407-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bacteriology, University of Wisconsin-Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8248780" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Carrier Proteins/metabolism ; DNA, Bacterial/*metabolism ; DNA-Binding Proteins/metabolism ; DNA-Directed RNA Polymerases/*metabolism ; Escherichia coli/enzymology/*genetics ; *Escherichia coli Proteins ; Integration Host Factors ; Molecular Sequence Data ; *Promoter Regions, Genetic ; Transcription Factors/metabolism ; Transcription, Genetic ; *rRNA Operon
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  • 36
    Publication Date: 1993-05-28
    Description: A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of Trypanosoma brucei.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Latif, F -- Tory, K -- Gnarra, J -- Yao, M -- Duh, F M -- Orcutt, M L -- Stackhouse, T -- Kuzmin, I -- Modi, W -- Geil, L -- New York, N.Y. -- Science. 1993 May 28;260(5112):1317-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, MD 21702-1201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493574" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Carcinoma, Renal Cell/genetics ; Chromosomes, Human, Pair 3 ; Cloning, Molecular ; Gene Deletion ; *Genes, Tumor Suppressor ; Humans ; Kidney Neoplasms/genetics ; Membrane Glycoproteins/chemistry/*genetics ; Molecular Sequence Data ; Mutation ; Open Reading Frames ; Pedigree ; Polymorphism, Genetic ; Tumor Cells, Cultured ; von Hippel-Lindau Disease/*genetics
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  • 37
    Publication Date: 1993-06-25
    Description: Female spotted hyenas exhibit male-like genitalia and dominance over males. Hyena ovarian tissues incubated in vitro produced large quantities of the steroid hormone precursor androstenedione. The activity of aromatase, which converts androstenedione to estrogen, was one-twentieth as great in hyena versus human placental homogenates. In comparison, the activity of 17 beta-hydroxysteroid dehydrogenase, which converts androstenedione to testosterone, was equal in the two homogenates. The limited aromatase activity may allow the hyena placenta to convert high circulating concentrations of androstenedione to testosterone, which results in virilization of the fetal external genitalia and possibly destruction of fetal ovarian follicles. Androstenedione production by residual ovarian stromal cells during reproductive life accounts for the epigenetic transmission of virilization in female spotted hyenas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yalcinkaya, T M -- Siiteri, P K -- Vigne, J L -- Licht, P -- Pavgi, S -- Frank, L G -- Glickman, S E -- CA-39825/CA/NCI NIH HHS/ -- MH-39917/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 25;260(5116):1929-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics, Gynecology, University of California School of Medicine, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8391165" target="_blank"〉PubMed〈/a〉
    Keywords: 17-Hydroxysteroid Dehydrogenases/metabolism ; Animals ; Aromatase/*metabolism ; Carnivora/embryology/*metabolism ; Corpus Luteum/metabolism ; Estradiol/biosynthesis ; Female ; Humans ; In Vitro Techniques ; Luteinizing Hormone/pharmacology ; Male ; Ovary/*metabolism ; Placenta/enzymology/*metabolism ; Pregnancy ; Progesterone/biosynthesis ; *Sex Differentiation ; Testosterone/*biosynthesis
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  • 38
    Publication Date: 1993-01-29
    Description: The phosphocarrier protein IIIGlc is an integral component of the bacterial phosphotransferase (PTS) system. Unphosphorylated IIIGlc inhibits non-PTS carbohydrate transport systems by binding to diverse target proteins. The crystal structure at 2.6 A resolution of one of the targets, glycerol kinase (GK), in complex with unphosphorylated IIIGlc, glycerol, and adenosine diphosphate was determined. GK contains a region that is topologically identical to the adenosine triphosphate binding domains of hexokinase, the 70-kD heat shock cognate, and actin. IIIGlc binds far from the catalytic site of GK, indicating that long-range conformational changes mediate the inhibition of GK by IIIGlc. GK and IIIGlc are bound by hydrophobic and electrostatic interactions, with only one hydrogen bond involving an uncharged group. The phosphorylation site of IIIGlc, His90, is buried in a hydrophobic environment formed by the active site region of IIIGlc and a 3(10) helix of GK, suggesting that phosphorylation prevents IIIGlc binding to GK by directly disrupting protein-protein interactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hurley, J H -- Faber, H R -- Worthylake, D -- Meadow, N D -- Roseman, S -- Pettigrew, D W -- Remington, S J -- 5-R37 GM38759/GM/NIGMS NIH HHS/ -- GM 42618-01A1/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):673-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology, University of Oregon, Eugene 97403.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430315" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Amino Acid Sequence ; Binding Sites ; Escherichia coli/*enzymology ; Escherichia coli Proteins ; Glycerol Kinase/*chemistry/*metabolism ; Hydrogen Bonding ; Models, Molecular ; Models, Structural ; Phosphoenolpyruvate Sugar Phosphotransferase System/*chemistry/*metabolism ; *Protein Structure, Secondary
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  • 39
    Publication Date: 1993-12-24
    Description: The elongated proteins of the spectrin family (dystrophin, alpha-actinin, and spectrin) contain tandemly repeated segments and form resilient cellular meshworks by cross-linking actin filaments. The structure of one of the repetitive segments of alpha-spectrin was determined at a 1.8 angstrom resolution. A segment consists of a three-helix bundle. A model of the interface between two tandem segments suggests that hydrophobic interactions between segments may constrain intersegment flexibility. The helix side chain interactions explain how mutations that are known to produce hemolytic anemias disrupt spectrin associations that sustain the integrity of the erythrocyte membrane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, Y -- Winograd, E -- Viel, A -- Cronin, T -- Harrison, S C -- Branton, D -- CA 13202/CA/NCI NIH HHS/ -- HL 17411/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 24;262(5142):2027-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266097" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Crystallization ; Drosophila ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Spectrin/*chemistry
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  • 40
    Publication Date: 1993-09-24
    Description: Intraperitoneal injection of epidermal growth factor (EGF) into mice resulted in the appearance in liver nuclei of three tyrosine phosphorylated proteins (84, 91, and 92 kilodaltons) within minutes after administration of EGF. Administration of interferon-gamma (IFN-gamma) resulted in the appearance in liver nuclei of two tyrosine phosphorylated proteins (84 and 91 kilodaltons). The 84- and 91-kilodalton proteins detected after either EGF or IFN-gamma administration were identified as the IFN-gamma activation factors (GAF). Furthermore, gel shift analysis revealed that these GAF proteins, detected after either EGF or IFN-gamma administration, specifically bound to the sis-inducible element of the c-fos promoter. Thus, GAF proteins participate in nuclear signaling in both IFN-gamma and EGF pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruff-Jamison, S -- Chen, K -- Cohen, S -- HD-00700/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 24;261(5129):1733-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8378774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Nucleus/drug effects/*metabolism ; DNA-Binding Proteins/*metabolism ; Epidermal Growth Factor/*pharmacology ; Genes, fos ; Interferon-Stimulated Gene Factor 3 ; Interferon-gamma/*pharmacology ; Liver/drug effects/metabolism ; Mice ; Molecular Sequence Data ; Phosphorylation ; Promoter Regions, Genetic ; STAT1 Transcription Factor ; *Trans-Activators ; Transcription Factors/*metabolism ; Tyrosine/*metabolism
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-16
    Description: Fertilization is accompanied by a transient increase in the concentration of intracellular Ca2+, which serves as a signal for initiating development. Some of the Ca2+ appears to be released from intracellular stores by the binding of inositol trisphosphate (IP3) to its receptor. However, in sea urchin eggs, other mechanisms appear to participate. Cyclic adenosine diphosphate--ribose (cADPR), a naturally occurring metabolite of nicotinamide adenine dinucleotide, is as potent as IP3 in mobilizing Ca2+ in sea urchin eggs. Experiments with antagonists of the cADPR and IP3 receptors revealed that both Ca2+ mobilizing systems were activated during fertilization. Blockage of either of the systems alone was not sufficient to prevent the sperm-induced Ca2+ transient. This study provides direct evidence for a physiological role of cADPR in the Ca2+ signaling process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, H C -- Aarhus, R -- Walseth, T F -- HD17484/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1993 Jul 16;261(5119):352-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Minnesota, Minneapolis 55455.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8392749" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate Ribose/analogs & derivatives/pharmacology ; Animals ; Calcium/*metabolism ; *Calcium Channels ; Cyclic ADP-Ribose ; Cyclic AMP/analogs & derivatives/pharmacology ; Female ; *Fertilization ; Heparin/pharmacology ; Inositol 1,4,5-Trisphosphate/pharmacology ; Inositol 1,4,5-Trisphosphate Receptors ; Ovum/*metabolism ; Receptors, Cell Surface/*physiology ; *Receptors, Cytoplasmic and Nuclear ; Sea Urchins ; Signal Transduction
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  • 42
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morell, V -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):683-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8342036" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Australia ; Contraception, Immunologic/*veterinary ; Ecology ; Female ; *Foxes/microbiology ; *Genetic Engineering ; Male ; Myxoma virus/genetics ; Pest Control, Biological/*methods ; *Rabbits/microbiology ; Viruses/*genetics
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  • 43
    Publication Date: 1993-05-21
    Description: The three-dimensional solution structure of the DNA binding domain (DBD) of the retinoid X receptor alpha (RXR alpha) was determined by nuclear magnetic resonance spectroscopy. The two zinc fingers of the RXR DBD fold to form a single structural domain that consists of two perpendicularly oriented helices and that resembles the corresponding regions of the glucocorticoid and estrogen receptors (GR and ER, respectively). However, in contrast to the DBDs of the GR and ER, the RXR DBD contains an additional helix immediately after the second zinc finger. This third helix mediates both protein-protein and protein-DNA interactions required for cooperative, dimeric binding of the RXR DBD to DNA. Identification of the third helix in the RXR DBD thus defines a structural feature required for selective dimerization of the RXR on hormone response elements composed of half-sites (5'-AGGTCA-3') arranged as tandem repeats.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, M S -- Kliewer, S A -- Provencal, J -- Wright, P E -- Evans, R M -- New York, N.Y. -- Science. 1993 May 21;260(5111):1117-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8388124" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; DNA/*metabolism ; DNA-Binding Proteins/*chemistry/metabolism ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/*chemistry/metabolism ; Oligodeoxyribonucleotides ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Cell Surface/*chemistry/metabolism ; *Receptors, Retinoic Acid ; Repetitive Sequences, Nucleic Acid ; Retinoid X Receptors ; *Transcription Factors ; Zinc Fingers
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  • 44
    Publication Date: 1993-04-30
    Description: A recessive mutation was identified in a family of transgenic mice that resulted in a reversal of left-right polarity (situs inversus) in 100 percent of the homozygous transgenic mice tested. Sequences that flanked the transgenic integration site were cloned and mapped to mouse chromosome 4, between the Tsha and Hxb loci. During early embryonic development, the direction of postimplantation turning, one of the earliest manifestations of left-right asymmetry, was reversed in homozygous transgenic embryos. This insertional mutation identifies a gene that controls embryonic turning and visceral left-right polarity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yokoyama, T -- Copeland, N G -- Jenkins, N A -- Montgomery, C A -- Elder, F F -- Overbeek, P A -- HD25340/HD/NICHD NIH HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 30;260(5108):679-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8480178" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Chromosome Mapping ; Cloning, Molecular ; Embryonic and Fetal Development/*genetics ; Female ; *Genes, Recessive ; Homozygote ; Male ; Mice ; Mice, Transgenic ; Mutagenesis, Insertional ; Situs Inversus/*genetics
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-04
    Description: Pectate lyases are secreted by pathogens and initiate soft-rot diseases in plants by cleaving polygalacturonate, a major component of the plant cell wall. The three-dimensional structure of pectate lyase C from Erwinia chrysanthemi has been solved and refined to a resolution of 2.2 angstroms. The enzyme folds into a unique motif of parallel beta strands coiled into a large helix. Within the core, the amino acids form linear stacks and include a novel asparagine ladder. The sequence similarities that pectate lyases share with pectin lyases, pollen and style proteins, and tubulins suggest that the parallel beta helix motif may occur in a broad spectrum of proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoder, M D -- Keen, N T -- Jurnak, F -- New York, N.Y. -- Science. 1993 Jun 4;260(5113):1503-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of California, Riverside 92521.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8502994" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Calcium ; Crystallography ; Isoenzymes/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Pectobacterium chrysanthemi/enzymology ; Polysaccharide-Lyases/*chemistry ; Protein Structure, Secondary ; *Protein Structure, Tertiary
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1993 Dec 3;262(5139):1512-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8248799" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Genetic Therapy/*methods ; HIV/genetics ; HIV Infections/*therapy ; Humans ; Molecular Sequence Data ; RNA, Catalytic/*genetics/metabolism/therapeutic use ; RNA, Viral/metabolism
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morell, V -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1722-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8511575" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Female ; *Genes, Recessive ; Genetic Diseases, Inborn ; Humans ; Male ; Monoamine Oxidase/deficiency/*genetics ; Mutation ; Pedigree ; *X Chromosome
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  • 48
    Publication Date: 1993-09-10
    Description: Activated autoreactive T cells are potentially pathogenic and regulated by clonotypic networks. Experimental autoimmune diseases can be treated by inoculation with autoreactive T cells (T cell vaccination). In the present study, patients with multiple sclerosis were inoculated with irradiated myelin basic protein (MBP)-reactive T cells. T cell responses to the inoculates were induced to deplete circulating MBP-reactive T cells in the recipients. Regulatory T cell lines isolated from the recipients inhibited T cells used for vaccination. The cytotoxicity of the CD8+ T cell lines was restricted by major histocompatibility antigens. Thus, clonotypic interactions regulating autoreactive T cells in humans can be induced by T cell vaccination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, J -- Medaer, R -- Stinissen, P -- Hafler, D -- Raus, J -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1451-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Multiple Sclerosis Research Unit, Dr. L. Willems Instituut, Diepenbeek, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7690157" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antigens, CD4/analysis ; Antigens, CD8/analysis ; Cell Line ; Epitopes/immunology ; Female ; Humans ; *Immunotherapy, Adoptive ; Lymphocyte Activation ; Male ; Middle Aged ; Multiple Sclerosis/immunology/*therapy ; Myelin Basic Protein/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocytes/*immunology ; Vaccination
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, E W -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):35-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8316856" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/chemistry/metabolism ; Actomyosin/chemistry ; Adenosine Triphosphate/metabolism ; Models, Biological ; Models, Molecular ; *Muscle Contraction ; Myosin Subfragments/*chemistry/metabolism ; *Protein Conformation ; Protein Structure, Secondary ; X-Ray Diffraction
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):452.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8424165" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; *Bioethics ; Brain Neoplasms/*therapy ; DNA, Recombinant ; Death ; *Ethical Review ; Federal Government ; Female ; *Genetic Therapy ; *Government Regulation ; Humans ; Middle Aged ; National Institutes of Health (U.S.) ; *Therapeutic Human Experimentation ; United States
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  • 51
    Publication Date: 1993-05-21
    Description: A potent neurotrophic factor that enhances survival of midbrain dopaminergic neurons was purified and cloned. Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer that is a distantly related member of the transforming growth factor-beta superfamily. In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake. These effects were relatively specific; GDNF did not increase total neuron or astrocyte numbers nor did it increase transmitter uptake by gamma-aminobutyric-containing and serotonergic neurons. GDNF may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, L F -- Doherty, D H -- Lile, J D -- Bektesh, S -- Collins, F -- New York, N.Y. -- Science. 1993 May 21;260(5111):1130-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Synergen, Inc., Boulder, CO 80301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493557" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Astrocytes/cytology/drug effects ; Base Sequence ; Cell Differentiation/drug effects ; Cell Line ; Cell Survival/drug effects ; Cells, Cultured ; Cloning, Molecular ; Dopamine/*biosynthesis ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Mesencephalon/cytology/*drug effects/metabolism ; Molecular Sequence Data ; Molecular Weight ; *Nerve Growth Factors ; Nerve Tissue Proteins/chemistry/genetics/isolation & purification/*pharmacology ; Neuroglia/*metabolism ; Neurons/cytology/*drug effects/metabolism ; Parkinson Disease/drug therapy ; Rats
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morimoto, R I -- New York, N.Y. -- Science. 1993 Mar 5;259(5100):1409-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Molecular and Cell Biology, Northwestern University, Evanston, IL 60201.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8451637" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; DNA/genetics/metabolism ; DNA-Binding Proteins/metabolism ; *Gene Expression Regulation ; Heat-Shock Proteins/*genetics ; Hot Temperature ; Humans ; Models, Genetic ; Molecular Sequence Data ; Transcription Factors/*metabolism ; *Transcription, Genetic
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thompson, L -- New York, N.Y. -- Science. 1993 Jan 8;259(5092):172.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8421780" target="_blank"〉PubMed〈/a〉
    Keywords: Advisory Committees ; Ethical Review ; Federal Government ; Female ; Genetic Therapy/*legislation & jurisprudence ; *Government Regulation ; Humans ; Interleukin-2/*genetics ; Middle Aged ; National Institutes of Health (U.S.) ; Neoplasms/*therapy ; Patient Selection ; Research Subjects ; United States
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friend, S H -- New York, N.Y. -- Science. 1993 Feb 5;259(5096):774-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Charlestown 02129.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430329" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crosses, Genetic ; Cyprinodontiformes/*genetics ; Female ; Fish Diseases/*genetics ; Genes, Tumor Suppressor ; *Genetic Predisposition to Disease ; Male ; Melanoma/genetics/*veterinary ; Models, Genetic ; Neoplasms/*genetics ; Proto-Oncogenes
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frisch, R E -- New York, N.Y. -- Science. 1993 Aug 27;261(5125):1103-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8356441" target="_blank"〉PubMed〈/a〉
    Keywords: *Adipose Tissue ; Body Composition ; Body Weight ; Female ; Humans ; *Menarche ; *Menstrual Cycle
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  • 56
    Publication Date: 1993-08-27
    Description: Better characterization of human immunodeficiency virus-type 1 (HIV-1) in patients with primary infection has important implications for the development of an acquired immunodeficiency syndrome (AIDS) vaccine because vaccine strategies should target viral isolates with the properties of transmitted viruses. In five HIV-1 seroconverters, the viral phenotype was found to be uniformly macrophage-tropic and non-syncytium-inducing. Furthermore, the viruses were genotypically homogeneous within each patient, but a common signature sequence was not discernible among transmitted viruses. In the two cases where the sexual partners were also studied, the sequences of the transmitted viruses matched best with minor variants in the blood of the transmitters. There was also a stronger pressure to conserve sequences in gp120 than in gp41, nef, and p17, suggesting that a selective mechanism is involved in transmission.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, T -- Mo, H -- Wang, N -- Nam, D S -- Cao, Y -- Koup, R A -- Ho, D D -- AI24030/AI/NIAID NIH HHS/ -- AI25541/AI/NIAID NIH HHS/ -- AI27742/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Aug 27;261(5125):1179-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Aaron Diamond AIDS Research Center, New York University School of Medicine, NY 10016.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8356453" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Line ; Female ; Gene Products, gag/chemistry/genetics ; Genes, Viral ; Genotype ; Giant Cells/physiology ; HIV Antigens/chemistry/genetics ; HIV Envelope Protein gp120/chemistry/*genetics ; HIV Envelope Protein gp41/chemistry/genetics ; HIV Infections/*microbiology/transmission ; HIV Seropositivity/microbiology ; HIV-1/chemistry/*genetics/*physiology ; Humans ; Macrophages ; Male ; Molecular Sequence Data ; Phenotype ; Sequence Alignment ; Sexual Partners ; *Viral Proteins ; Virus Replication ; gag Gene Products, Human Immunodeficiency Virus
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  • 57
    Publication Date: 1993-05-07
    Description: A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of "familial" cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aaltonen, L A -- Peltomaki, P -- Leach, F S -- Sistonen, P -- Pylkkanen, L -- Mecklin, J P -- Jarvinen, H -- Powell, S M -- Jen, J -- Hamilton, S R -- CA 35494/CA/NCI NIH HHS/ -- CA 47527/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 May 7;260(5109):812-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Genetics, University of Helsinki, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8484121" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosome Mapping ; *Chromosomes, Human, Pair 2 ; Colonic Neoplasms/*genetics ; Colorectal Neoplasms/*genetics ; DNA, Satellite/genetics ; Female ; Genetic Markers ; Humans ; Lod Score ; Male ; Mutation ; Pedigree ; Polymorphism, Genetic ; Rectal Neoplasms/genetics ; Repetitive Sequences, Nucleic Acid
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  • 58
    Publication Date: 1993-10-29
    Description: A 24-amino acid peptide designed to solubilize integral membrane proteins has been synthesized. The design was for an amphipathic alpha helix with a "flat" hydrophobic surface that would interact with a transmembrane protein as a detergent. When mixed with peptide, 85 percent of bacteriorhodopsin and 60 percent of rhodopsin remained in solution over a period of 2 days in their native forms. The crystal structure of peptide alone showed it to form an antiparallel four-helix bundle in which monomers interact, flat surface to flat surface, as predicted.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schafmeister, C E -- Miercke, L J -- Stroud, R M -- GM24485/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 29;262(5134):734-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235592" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriorhodopsins/chemistry ; Crystallography, X-Ray ; Detergents/chemical synthesis/*chemistry ; Drug Design ; Membrane Proteins/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemical synthesis/*chemistry ; Protein Conformation ; Protein Structure, Secondary ; Rhodopsin/chemistry
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-18
    Description: Mammalian apolipoprotein B (apo B) exists in two forms, each the product of a single gene. The shorter form, apo B48, arises by posttranscriptional RNA editing whereby cytidine deamination produces a UAA termination codon. A full-length complementary DNA clone encoding an apo B messenger RNA editing protein (REPR) was isolated from rat small intestine. The 229-residue protein contains consensus phosphorylation sites and leucine zipper domains. HepG2 cell extracts acquire editing activity when mixed with REPR from oocyte extracts. REPR is essential for apo B messenger RNA editing, and the isolation and characterization of REPR may lead to the identification of other eukaryotic RNA editing proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teng, B -- Burant, C F -- Davidson, N O -- DK-42086/DK/NIDDK NIH HHS/ -- HL-38180/HL/NHLBI NIH HHS/ -- KO-4 HL-02166/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1816-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Chicago, IL 60637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8511591" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Apolipoproteins B/*genetics ; Base Sequence ; Cell Line ; *Cloning, Molecular ; Cytidine Deaminase/chemistry/*genetics ; Humans ; Intestine, Small/chemistry ; Leucine Zippers ; Molecular Sequence Data ; Molecular Weight ; Open Reading Frames ; Phosphorylation ; *RNA Editing ; Rats ; Tumor Cells, Cultured
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myers, R M -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):942-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of California, San Francisco 94143-0444.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8094900" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cloning, Molecular ; DNA/*chemistry ; DNA Probes ; Female ; Gene Deletion ; Humans ; Male ; Nucleic Acid Hybridization/*methods ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length
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  • 61
    Publication Date: 1993-02-19
    Description: The T cell receptor (TCR) requirements in the pathogenesis of insulin-dependent diabetes were examined with transgenic NOD mice bearing nondisease-related TCR alpha and beta chains. In both TCR beta and TCR alpha beta transgenic NOD mice the beta chain transgene was expressed by 〉 98% of peripheral T cells. The alpha chain transgene was also highly expressed. Insulitis developed in both sets of transgenic animals with most of the lymphocytes in the lesion expressing the transgenic beta chain and with depletion of the endogenous TCR V beta genes. Nonetheless, NOD animals transgenic for TCR beta and TCR alpha beta developed diabetes similar to controls. Thus, skewing the TCR repertoire did not diminish autoimmune susceptibility in NOD mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lipes, M A -- Rosenzweig, A -- Tan, K N -- Tanigawa, G -- Ladd, D -- Seidman, J G -- Eisenbarth, G S -- New York, N.Y. -- Science. 1993 Feb 19;259(5098):1165-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Joslin Diabetes Center, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8267690" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Base Sequence ; Crosses, Genetic ; Diabetes Mellitus, Type 2/genetics/immunology/*physiopathology ; Female ; Gene Rearrangement, T-Lymphocyte ; Islets of Langerhans/immunology/pathology ; Male ; Mice ; Mice, Inbred NOD/*physiology ; Mice, Transgenic ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Pancreatic Diseases/genetics/immunology/pathology ; Polymerase Chain Reaction/methods ; Receptors, Antigen, T-Cell, alpha-beta/genetics/*physiology ; T-Lymphocytes/*immunology/pathology
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-24
    Description: What determines the precise sites of cleavage in the two transesterification reactions of messenger RNA (mRNA) splicing is a major unsolved question. Mutation of the invariant G (guanosine) at position 5 of 5' splice sites in Saccharomyces cerevisiae introns activates cleavage at nearby aberrant sites. A genetic approach was used to test the hypothesis that a base-pairing interaction between the 5' splice site and the invariant ACAGAG sequence of U6 is a determinant of 5' splice site choice. Mutations in U6 or the intron (or both) that were predicted to stabilize the interaction suppressed aberrant cleavage and increased normal cleavage. In addition, a mutation in the ACAGAG sequence suppressed mutations of the 3' splice site dinucleotide. These data can fit a model for the spliceosomal active site comprised of a set of RNA-RNA interactions between the intron, U2 and U6.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lesser, C F -- Guthrie, C -- GM21119/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 24;262(5142):1982-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Scientist Training Program, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266093" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites/genetics ; Genes, Reporter ; Introns/genetics ; Models, Genetic ; Molecular Sequence Data ; *Mutation ; Nucleic Acid Conformation ; RNA Splicing/*genetics ; RNA, Small Nuclear/*genetics ; Saccharomyces cerevisiae/genetics ; Suppression, Genetic
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  • 63
    Publication Date: 1993-08-13
    Description: The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Corder, E H -- Saunders, A M -- Strittmatter, W J -- Schmechel, D E -- Gaskell, P C -- Small, G W -- Roses, A D -- Haines, J L -- Pericak-Vance, M A -- New York, N.Y. -- Science. 1993 Aug 13;261(5123):921-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8346443" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Aging ; *Alleles ; Alzheimer Disease/*genetics/metabolism/mortality ; Amyloid beta-Peptides/metabolism ; Apolipoprotein E4 ; Apolipoproteins E/*genetics/physiology ; Female ; *Gene Frequency ; Genotype ; Homozygote ; Humans ; Linkage Disequilibrium ; Male ; Risk Factors ; Survival Rate
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  • 64
    Publication Date: 1993-07-16
    Description: Propagating Ca2+ waves are a characteristic feature of Ca(2+)-linked signal transduction pathways. Intracellular Ca2+ waves are formed by regenerative stimulation of Ca2+ release from intracellular stores by Ca2+ itself. Mechanisms that rely on either inositol trisphosphate or ryanodine receptor channels have been proposed to account for Ca2+ waves in various cell types. Both channel types contributed to the Ca2+ wave during fertilization of sea urchin eggs. Alternative mechanisms of Ca2+ release imply redundancy but may also allow for modulation and diversity in the generation of Ca2+ waves.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galione, A -- McDougall, A -- Busa, W B -- Willmott, N -- Gillot, I -- Whitaker, M -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 1993 Jul 16;261(5119):348-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Oxford University, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8392748" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate Ribose/analogs & derivatives/pharmacology ; Adenosine Triphosphate/metabolism ; Animals ; Caffeine/pharmacology ; Calcium/*metabolism/pharmacology ; *Calcium Channels ; Cyclic ADP-Ribose ; Female ; *Fertilization ; Heparin/pharmacology ; Inositol 1,4,5-Trisphosphate/pharmacology ; Inositol 1,4,5-Trisphosphate Receptors ; Muscle Proteins/drug effects/*physiology ; Ovum/drug effects/*metabolism ; Receptors, Cell Surface/drug effects/*physiology ; *Receptors, Cytoplasmic and Nuclear ; Ryanodine/pharmacology ; Ryanodine Receptor Calcium Release Channel ; Sea Urchins ; Signal Transduction ; Thimerosal/pharmacology ; Xenopus
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  • 65
    Publication Date: 1993-01-15
    Description: A variety of tumors are potentially immunogenic but do not stimulate an effective anti-tumor immune response in vivo. Tumors may be capable of delivering antigen-specific signals to T cells, but may not deliver the costimulatory signals necessary for full activation of T cells. Expression of the costimulatory ligand B7 on melanoma cells was found to induce the rejection of a murine melanoma in vivo. This rejection was mediated by CD8+ T cells; CD4+ T cells were not required. These results suggest that B7 expression renders tumor cells capable of effective antigen presentation, leading to their eradication in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Townsend, S E -- Allison, J P -- CA57986/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 15;259(5093):368-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7678351" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD80 ; Antigens, Surface/genetics/*immunology ; CD4-Positive T-Lymphocytes/immunology ; Cross Reactions ; Female ; Gene Expression Regulation ; Genetic Vectors ; Ligands ; *Lymphocyte Activation ; Melanoma/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Nude ; T-Lymphocytes, Regulatory/*immunology ; Transfection ; Tumor Cells, Cultured
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newlon, C S -- New York, N.Y. -- Science. 1993 Dec 17;262(5141):1830-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry-New Jersey Medical School, Newark 07103.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266070" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA Replication ; DNA, Fungal/genetics/metabolism ; DNA-Binding Proteins/chemistry/*genetics ; Fungal Proteins/chemistry/*genetics/metabolism ; *Gene Expression Regulation, Fungal ; Genes, Fungal ; Molecular Sequence Data ; Mutation ; Origin Recognition Complex ; *Replicon ; Repressor Proteins/*genetics/metabolism ; Saccharomyces cerevisiae/*genetics ; Transcription, Genetic
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-06
    Description: Endonuclease G (Endo G) is widely distributed among animals and cleaves DNA at double-stranded (dG)n.(dC)n and at single-stranded (dC)n tracts. Endo G is synthesized as a propeptide with an amino-terminal presequence that targets the nuclease to mitochondria. Endo G can also be detected in extranucleolar chromatin. In addition to deoxyribonuclease activities, Endo G also has ribonuclease (RNase) and RNase H activities and specifically cleaves mouse mitochondrial RNA and DNA-RNA substrates containing the origin of heavy-strand DNA replication (OH). The cleavage sites match those found in vivo, indicating that Endo G is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cote, J -- Ruiz-Carrillo, A -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):765-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Center, Medical School of Laval University, L'Hotel-Dieu de Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7688144" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Cell Nucleus/enzymology ; DNA/genetics ; *DNA Replication ; DNA, Mitochondrial/*metabolism ; Endodeoxyribonucleases/chemistry/genetics/*metabolism ; Genetic Vectors ; Mitochondria/enzymology ; Molecular Sequence Data ; RNA/*metabolism ; Ribonuclease H/metabolism ; Ribonucleases/metabolism ; Transfection
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  • 68
    Publication Date: 1993-09-10
    Description: Expression of either the CD4 or CD8 glycoproteins discriminates two functionally distinct lineages of T lymphocytes. A null mutation in the gene encoding CD4 impairs the development of the helper cell lineage that is normally defined by CD4 expression. Infection of CD4-null mice with Leishmania has revealed a population of functional helper T cells that develops despite the absence of CD4. These CD8- alpha beta T cell receptor+ T cells are major histocompatibility complex class II-restricted and produce interferon-gamma when challenged with parasite antigens. These results indicate that T lymphocyte lineage commitment and peripheral function need not depend on the function of CD4.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locksley, R M -- Reiner, S L -- Hatam, F -- Littman, D R -- Killeen, N -- AI30663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1448-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, San Francisco 94143-0654.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8367726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/genetics/*immunology ; Antigens, CD8/immunology ; Antigens, Protozoan/immunology ; B-Lymphocytes/immunology ; Base Sequence ; CD4-CD8 Ratio ; Histocompatibility Antigens Class II/immunology ; Hypersensitivity, Delayed ; Interferon-gamma/biosynthesis/immunology ; Leishmania tropica/*immunology ; Leishmaniasis, Cutaneous/*immunology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Oligodeoxyribonucleotides ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes, Helper-Inducer/*immunology
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  • 69
    Publication Date: 1993-08-20
    Description: The self-splicing bl1 intron lariat from mitochondria of Saccharomyces cerevisiae catalyzed the insertion of nucleotidyl monomers derived from the 3' end of a donor RNA into an acceptor RNA in a 3' to 5' direction in vitro. In this catalyzed reaction, the site specificity provided by intermolecular base pair interactions, the formation of chimeric intermediates, the polarity of the nucleotidyl insertion, and its reversibility all resemble such properties in previously proposed models of RNA editing in kinetoplastid mitochondria. These results suggest that RNA editing occurs by way of a concerted, two-step transesterification mechanism and that RNA splicing and RNA editing might be prebiotically related mechanisms; possibly, both evolved from a primordial demand for self-replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mueller, M W -- Hetzer, M -- Schweyen, R J -- New York, N.Y. -- Science. 1993 Aug 20;261(5124):1035-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vienna Biocenter, Institute for Microbiology and Genetics, University of Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8351516" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*metabolism ; Base Sequence ; Esterification ; *Introns ; Mitochondria/metabolism ; Molecular Sequence Data ; *RNA Editing ; RNA Splicing ; RNA, Catalytic/*metabolism ; RNA, Fungal/*metabolism ; RNA, Guide/*metabolism ; Saccharomyces cerevisiae/genetics/metabolism
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barlow, D P -- New York, N.Y. -- Science. 1993 Apr 16;260(5106):309-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Institute of Molecular Pathology, Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8469984" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA/genetics/*metabolism ; *Dosage Compensation, Genetic ; Embryo, Mammalian/metabolism ; Fathers ; Female ; *Gene Expression Regulation ; Insulin-Like Growth Factor II/genetics ; Male ; Methylation ; Mice ; Models, Genetic ; Mothers ; Oocytes/metabolism ; Receptor, IGF Type 2/genetics ; Spermatozoa/metabolism
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-09-03
    Description: The POU-type homeodomain protein UNC-86 and the LIM-type homeodomain protein MEC-3, which specify neuronal cell fate in the nematode Caenorhabditis elegans, bind cooperatively as a heterodimer to the mec-3 promoter. Heterodimer formation increases DNA binding stability and, therefore, increases DNA binding specificity. The in vivo significance of this heterodimer formation in neuronal differentiation is suggested by (i) a loss-of-function mec-3 mutation whose product in vitro binds DNA well but forms heterodimers with UNC-86 poorly and (ii) a mec-3 mutation with wild-type function whose product binds DNA poorly but forms heterodimers well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xue, D -- Tu, Y -- Chalfie, M -- GM30997/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 3;261(5126):1324-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8103239" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Caenorhabditis elegans/genetics/*metabolism ; *Caenorhabditis elegans Proteins ; Cell Differentiation ; DNA/*metabolism ; Genes, Helminth ; *Genes, Homeobox ; Helminth Proteins/chemistry/genetics/*metabolism ; *Homeodomain Proteins ; LIM-Homeodomain Proteins ; Molecular Sequence Data ; Neurons/cytology ; Oligodeoxyribonucleotides/metabolism ; POU Domain Factors ; Promoter Regions, Genetic ; Transcription Factors/chemistry/genetics/*metabolism
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leccese, A P -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):665.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8204122" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*prevention & control ; Adolescent ; Adult ; Female ; Humans ; Male ; Risk-Taking ; *Sexual Behavior ; *Street Drugs ; *Substance-Related Disorders
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  • 73
    Publication Date: 1993-12-17
    Description: The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is an essential component of high- and intermediate-affinity IL-2 receptors. IL-2R gamma was demonstrated to be a component of the IL-4 receptor on the basis of chemical cross-linking data, the ability of IL-2R gamma to augment IL-4 binding affinity, and the requirement for IL-2R gamma in IL-4-mediated phosphorylation of insulin receptor substrate-1. The observation that IL-2R gamma is a functional component of the IL-4 receptor, together with the finding that IL-2R gamma associates with the IL-7 receptor, begins to elucidate why deficiency of this common gamma chain (gamma c) has a profound effect on lymphoid function and development, as seen in X-linked severe combined immunodeficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Russell, S M -- Keegan, A D -- Harada, N -- Nakamura, Y -- Noguchi, M -- Leland, P -- Friedmann, M C -- Miyajima, A -- Puri, R K -- Paul, W E -- New York, N.Y. -- Science. 1993 Dec 17;262(5141):1880-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266078" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Cell Line, Transformed ; Genetic Linkage ; Humans ; Insulin Receptor Substrate Proteins ; Interleukin-4/metabolism ; L Cells (Cell Line) ; Mice ; Molecular Sequence Data ; Phosphoproteins/metabolism ; Phosphorylation ; Receptors, Interleukin-2/chemistry/genetics/*metabolism ; Receptors, Interleukin-4 ; Receptors, Mitogen/chemistry/genetics/*metabolism ; Severe Combined Immunodeficiency/genetics/immunology ; Signal Transduction ; Transfection ; X Chromosome
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  • 74
    Publication Date: 1993-09-24
    Description: Growth factors and cytokines act through cell surface receptors with different biochemical properties. Yet each type of receptor can elicit similar as well as distinct biological responses in target cells, suggesting that distinct classes of receptors activate common gene sets. Epidermal growth factor, interferon-gamma, and interleukin-6 all activated, through direct tyrosine phosphorylation, latent cytoplasmic transcription factors that recognized similar DNA elements. However, different ligands activated different patterns of factors with distinct DNA-binding specificities in the same and different cells. Thus, unrelated receptors may activate a common nuclear signal transduction pathway that, through differential use of latent cytoplasmic proteins, permits these receptors to regulate both common and unique sets of genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sadowski, H B -- Shuai, K -- Darnell, J E Jr -- Gilman, M Z -- AI32489/AI/NIAID NIH HHS/ -- CA09311/CA/NCI NIH HHS/ -- CA45642/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 24;261(5129):1739-44.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, NY 11724.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8397445" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Nucleus/metabolism ; Cytokines/metabolism/*pharmacology ; DNA-Binding Proteins/*metabolism ; Epidermal Growth Factor/pharmacology ; Growth Substances/metabolism/pharmacology ; Humans ; Interferon-Stimulated Gene Factor 3 ; Interferon-gamma/pharmacology ; Interleukin-6/pharmacology ; Molecular Sequence Data ; Phosphorylation ; Receptors, Cell Surface/*metabolism ; *Signal Transduction ; Transcription Factors/*metabolism ; Tumor Cells, Cultured ; Tyrosine/metabolism
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  • 75
    Publication Date: 1993-04-09
    Description: The myotonic dystrophy mutation has recently been identified; however, the molecular mechanism of the disease is still unknown. The sequence of the myotonin-protein kinase gene was determined, and messenger RNA spliced forms were identified in various tissues. Antisera were developed for analytical studies. Quantitative reverse transcription-polymerase chain reaction and radioimmunoassay were used to demonstrate that decreased levels of the messenger RNA and protein expression are associated with the adult form of myotonic dystrophy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, Y H -- Friedman, D L -- Richards, S -- Pearlman, J A -- Gibbs, R A -- Pizzuti, A -- Ashizawa, T -- Perryman, M B -- Scarlato, G -- Fenwick, R G Jr -- P30-HG00210/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 9;260(5105):235-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8469976" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Alternative Splicing ; Amino Acid Sequence ; Base Sequence ; Gene Expression ; Humans ; Molecular Sequence Data ; Molecular Weight ; Muscles/chemistry/*metabolism ; Myotonic Dystrophy/*genetics/metabolism ; Myotonin-Protein Kinase ; Polymerase Chain Reaction ; Protein Kinases/biosynthesis/chemistry/*genetics ; *Protein-Serine-Threonine Kinases ; RNA, Messenger/*genetics
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-03-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savakis, C -- Doelz, R -- New York, N.Y. -- Science. 1993 Mar 19;259(5102):1677-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8456288" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA/*chemistry ; Databases, Factual/*standards ; Humans
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  • 77
    Publication Date: 1993-01-08
    Description: Synthetic peptides corresponding to microbial epitopes stimulate T cell immunity but their immunogenicity is poor and their half-lives are short. A viral epitope inserted into the complementarity-determining region 3 (CDR3) loop of the heavy chain of a self immunoglobulin (Ig) molecule was generated from the Ig context and was presented by I-Ed class II molecules to virus-specific, CD4+ T cells. Chimeric Ig-peptide was presented 100 to 1000 times more efficiently than free synthetic peptide and was able to prime virus-specific T cells in vivo. These features suggest that antigenized Ig can provide an improved and safe vaccine for the presentation of microbial and other peptides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zaghouani, H -- Steinman, R -- Nonacs, R -- Shah, H -- Gerhard, W -- Bona, C -- AI13013/AI/NIAID NIH HHS/ -- AI18316/AI/NIAID NIH HHS/ -- AI24460/AI/NIAID NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Jan 8;259(5092):224-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7678469" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigen-Presenting Cells/*immunology ; Antigens, Viral/*immunology ; Arsenic/immunology ; *Arsenicals ; Base Sequence ; CD4-Positive T-Lymphocytes/immunology ; DNA/genetics ; Epitopes/*immunology ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins, Viral/genetics/immunology ; Histocompatibility Antigens Class II/immunology ; Immunoglobulin Heavy Chains/genetics/immunology ; Immunoglobulin Variable Region/genetics/immunology ; Immunoglobulins/genetics/*immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Mutagenesis ; Receptors, Fc/immunology ; Recombinant Fusion Proteins/immunology ; Transfection
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  • 78
    Publication Date: 1993-11-19
    Description: Humanized antibodies are highly efficient as immunotherapeutic reagents and have many advantages over rodent antibodies. A mouse strain was generated by gene targeting to replace the mouse kappa light chain constant (C) region gene with the human C kappa gene. Mice homozygous for the replacement mutation (C kappa R) produced normal concentrations of serum antibodies, most of which carry chimeric kappa light chains, and mounted normal immune responses to hapten-protein conjugates. This technology provides a feasible option for the generation of high-affinity humanized antibodies by means of the powerful somatic hypermutation-selection mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zou, Y R -- Gu, H -- Rajewsky, K -- New York, N.Y. -- Science. 1993 Nov 19;262(5137):1271-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genetics, University of Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235658" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/*immunology ; Base Sequence ; Gene Rearrangement ; *Genes, Immunoglobulin ; Humans ; Immunoglobulin Constant Regions/*biosynthesis/genetics ; Immunoglobulin Isotypes/biosynthesis ; Immunoglobulin kappa-Chains/*biosynthesis/genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; Recombinant Fusion Proteins/biosynthesis ; Stem Cells ; Transfection
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-03-19
    Description: The unfertilized eggs of vertebrates are arrested in metaphase of meiosis II because of the activity of cytostatic factor (CSF). Xenopus CSF is thought to contain the product of the Mos proto-oncogene, but other proteins synthesized during meiosis II are also required for arrest induced by CSF. In Xenopus oocytes, ablation of synthesis of cyclin-dependent kinase 2 (Cdk2) during meiosis resulted in absence of the metaphase II block, even though the Mosxe protein kinase was fully active at metaphase. Introduction of purified Cdk2 restored metaphase II arrest, and increasing the amount of Cdk2 during meiosis I (when Mosxe is present) led to metaphase arrest at meiosis I. These data indicate that metaphase arrest is a result of cooperation between a proto-oncogene kinase and a cyclin-dependent kinase and illustrate the interaction of a cell growth regulator with a cell cycle control element.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gabrielli, B G -- Roy, L M -- Maller, J L -- F32 CA0981/CA/NCI NIH HHS/ -- GM26743/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Mar 19;259(5102):1766-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Colorado School of Medicine, Denver 80262.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8456304" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *CDC2-CDC28 Kinases ; Cyclin-Dependent Kinase 2 ; *Cyclin-Dependent Kinases ; Female ; Meiosis/*physiology ; Metaphase/*physiology ; Molecular Sequence Data ; Oligonucleotides, Antisense/pharmacology ; Oocytes/*cytology/drug effects/metabolism ; Phosphorylation ; Poly A/metabolism ; Progesterone/pharmacology ; Protein Kinases/genetics/*physiology ; *Protein-Serine-Threonine Kinases ; *Proto-Oncogene Proteins c-mos/metabolism/*physiology ; RNA, Messenger/metabolism ; Xenopus ; Xenopus Proteins
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  • 80
    Publication Date: 1993-07-02
    Description: The enhancer for the immunoglobulin mu heavy chain gene (IgH) activates a heterologous gene at the pre-B cell stage of B lymphocyte differentiation. A lymphoid-specific element, microB, is necessary for enhancer function in pre-B cells. A microB binding protein is encoded by the PU.1/Spi-1 proto-oncogene. Another sequence element, microA, was identified in the mu enhancer that binds the product of the ets-1 proto-oncogene. The microA motif was required for microB-dependent enhancer activity, which suggests that a minimal B cell-specific enhancer is composed of both the PU.1 and Ets-1 binding sites. Co-expression of both PU.1 and Ets-1 in nonlymphoid cells trans-activated reporter plasmids that contained the minimal mu enhancer. These results implicate two members of the Ets family in the activation of IgH gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nelsen, B -- Tian, G -- Erman, B -- Gregoire, J -- Maki, R -- Graves, B -- Sen, R -- 1K04GM00563/GM/NIGMS NIH HHS/ -- GM38663/GM/NIGMS NIH HHS/ -- GM38925/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):82-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rosenstiel Research Center, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8316859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/cytology/*metabolism ; Base Sequence ; Binding Sites ; Cell Differentiation ; Cell Line ; DNA-Binding Proteins/*genetics/metabolism ; *Enhancer Elements, Genetic ; Female ; Genes, Immunoglobulin ; Humans ; Immunoglobulin mu-Chains/*genetics ; Molecular Sequence Data ; Mutation ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-ets ; Retroviridae Proteins, Oncogenic ; Transcription Factors/*genetics/metabolism
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  • 81
    Publication Date: 1993-10-08
    Description: The TATA-binding protein (TBP) is required for transcription by all three nuclear RNA polymerases. TBP was subjected to regional codon randomization, a codon-based mutagenesis method that generates complex yet compact protein libraries. Analysis of 186 temperature-sensitive TBP mutants yielded 65 specifically defective in transcription by RNA polymerase III (Pol III). These mutants map to a limited TBP surface that may interact with Tds4, a component of the Pol III transcription factor TFIIIB. Strains that contain the Pol III-defective derivatives have increased amounts of messenger RNA, which suggests that competition among TBP-interacting factors for limiting quantities of TBP determines the ratio of Pol II and Pol III transcription in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cormack, B P -- Struhl, K -- GM 30186/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 8;262(5131):244-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211143" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Arabidopsis/genetics ; Base Sequence ; *Codon ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutagenesis ; RNA Polymerase III/*metabolism ; RNA, Messenger/genetics ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Random Allocation ; Saccharomyces cerevisiae/genetics ; *TATA Box ; TATA-Box Binding Protein ; Temperature ; Transcription Factor TFIIIB ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcription, Genetic
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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-02
    Description: The diversity of the T cell receptor repertoire is generated by rearrangement of gene elements in immature thymocytes. To identify a thymic signal that induces this rearrangement, a variety of agents were tested for their ability to induce rearrangement of the T cell receptor beta gene in suspensions of thymocytes from mouse embryos at day 14 of gestation. Of 16 agents tested, only interleukin-7 (IL-7) induced V(D)J gene rearrangement and sustained expression of the RAG-1 and RAG-2 genes, which are known to control rearrangement. These data implicate IL-7, a cytokine that is abundantly expressed in embryonic thymus, in driving gene rearrangement during early T cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muegge, K -- Vila, M P -- Durum, S K -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):93-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Carcinogenesis and Development Program, Program Resources Inc./Dyncorp, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7686307" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Cell Survival/drug effects ; Cells, Cultured ; *DNA-Binding Proteins ; Gene Expression ; *Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Genes, RAG-1 ; Hematopoietic Cell Growth Factors/pharmacology ; Interleukin-7/*pharmacology ; Ionomycin/pharmacology ; Mice ; Molecular Sequence Data ; Organ Culture Techniques ; Proteins/genetics ; Stem Cell Factor ; T-Lymphocytes/cytology/*immunology ; Tetradecanoylphorbol Acetate/pharmacology ; Thymus Gland/embryology/immunology ; Tumor Cells, Cultured
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  • 83
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Newman, L S -- ES00173/ES/NIEHS NIH HHS/ -- ES06538/ES/NIEHS NIH HHS/ -- HL273353/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 8;262(5131):197-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Occupational and Environmental Medicine Division, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8105535" target="_blank"〉PubMed〈/a〉
    Keywords: Antigen-Presenting Cells/immunology ; Berylliosis/*etiology/genetics/immunology/prevention & control ; Beryllium/*adverse effects/immunology ; Female ; Genes, MHC Class II ; Genetic Markers ; Glutamates ; Glutamic Acid ; HLA-DP Antigens/chemistry/*genetics/immunology ; Humans ; Male ; *Occupational Exposure ; Risk Factors ; T-Lymphocytes, Helper-Inducer/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 84
    Publication Date: 1993-06-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benhorin, J -- Kalman, Y M -- Medina, A -- Towbin, J -- Rave-Harel, N -- Dyer, T D -- Blangero, J -- MacCluer, J W -- Kerem, B S -- 5R01-HL-33843/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 25;260(5116):1960-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8316839" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Alleles ; Child ; Female ; Genetic Linkage ; Humans ; Long QT Syndrome/*genetics ; Male ; Pedigree ; Phenotype
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  • 85
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crease, R -- New York, N.Y. -- Science. 1993 Mar 12;259(5101):1530-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8456280" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Canada ; Child ; Female ; Government Agencies ; Humans ; *Mothers ; *Periodicals as Topic ; Publishing ; *Social Problems ; *Women, Working
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  • 86
    Publication Date: 1993-12-10
    Description: A general strategy is described for the de novo design of proteins. In this strategy the sequence locations of hydrophobic and hydrophilic residues were specified explicitly, but the precise identities of the side chains were not constrained and varied extensively. This strategy was tested by constructing a large collection of synthetic genes whose protein products were designed to fold into four-helix bundle proteins. Each gene encoded a different amino acid sequence, but all sequences shared the same pattern of polar and nonpolar residues. Characterization of the expressed proteins indicated that most of the designed sequences folded into compact alpha-helical structures. Thus, a simple binary code of polar and nonpolar residues arranged in the appropriate order can drive polypeptide chains to collapse into globular alpha-helical folds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kamtekar, S -- Schiffer, J M -- Xiong, H -- Babik, J M -- Hecht, M H -- New York, N.Y. -- Science. 1993 Dec 10;262(5140):1680-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Princeton University, NJ 08544.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8259512" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Codon ; Gene Library ; Genes, Synthetic ; Molecular Sequence Data ; Molecular Weight ; Oligodeoxyribonucleotides ; *Protein Conformation ; *Protein Engineering ; Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry/genetics/isolation & purification
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-09
    Description: The regulation of transcription requires complex interactions between proteins bound to DNA sequences that are often separated by hundreds of base pairs. As demonstrated by a nuclear ligation assay, the distal enhancer and the proximal promoter regions of the rat prolactin gene were found to be juxtaposed. By acting through its receptor bound to the distal enhancer, estrogen stimulated the interaction between the distal and proximal regulatory regions two- to threefold compared to control values. Thus, the chromatin structure of the prolactin gene may facilitate the occurrence of protein-protein interactions between transcription factors bound to widely separated regulatory elements.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cullen, K E -- Kladde, M P -- Seyfred, M A -- DK42731/DK/NIDDK NIH HHS/ -- T32HD07048/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1993 Jul 9;261(5118):203-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Vanderbilt University, Nashville, TN 37235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8327891" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Cell Nucleus/metabolism ; Chromatin/*chemistry/metabolism ; DNA/chemistry/metabolism ; Deoxyribonucleases, Type II Site-Specific ; *Enhancer Elements, Genetic ; Estrogens/metabolism ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction ; Prolactin/*genetics ; *Promoter Regions, Genetic ; Protein Conformation ; Protein Folding ; Rats ; Receptors, Estrogen/metabolism ; Regulatory Sequences, Nucleic Acid ; *Transcription, Genetic
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  • 88
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-04-02
    Description: Lesions in the transcribed strand block transcription and are repaired more rapidly than lesions in the nontranscribed (coding) strand which do not block RNA polymerase (RNAP). It has been shown previously that in Escherichia coli the mfd (mutation frequency decline) gene is necessary for strand-specific repair. The mfd gene was cloned and sequenced and the Mfd protein was purified and used to reconstitute strand-specific repair in a completely defined system. The mfd gene encodes a protein of 130 kilodaltons and contains the so-called "helicase motifs," a leucine zipper motif, and regions of sequence similarity to UvrB and RecG proteins. The Mfd protein was shown to (i) displace RNAP stalled at a lesion in an adenosine triphosphate-dependent reaction, (ii) bind to the damage recognition subunit (UvrA) of the excision nuclease, and (iii) stimulate the repair of the transcribed strand only when transcription is taking place. Thus, Mfd appears to target the transcribed strand for repair by recognizing a stalled RNAP and actively recruiting the repair enzyme to the transcription blocking lesion as it dissociates the stalled RNAP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Selby, C P -- Sancar, A -- New York, N.Y. -- Science. 1993 Apr 2;260(5104):53-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8465200" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Proteins/chemistry/*genetics/metabolism ; Base Sequence ; Binding Sites ; Cloning, Molecular ; *DNA Helicases ; DNA Repair/*genetics ; DNA, Bacterial/metabolism ; DNA-Directed RNA Polymerases/metabolism ; Endodeoxyribonucleases/metabolism ; Escherichia coli/*genetics ; *Escherichia coli Proteins ; Leucine Zippers ; Molecular Sequence Data ; Multienzyme Complexes/chemistry/genetics ; Mutation/genetics ; Transcription Factors/chemistry/*genetics/metabolism ; *Transcription, Genetic
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nowak, R -- New York, N.Y. -- Science. 1993 Dec 17;262(5141):1818.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266068" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Genetic Linkage ; Humans ; Mice ; Mutation ; Receptors, Interleukin/chemistry/genetics/metabolism ; Receptors, Interleukin-2/*chemistry/genetics/metabolism ; Receptors, Interleukin-4 ; Receptors, Interleukin-7 ; Receptors, Mitogen/*chemistry/genetics/metabolism ; Severe Combined Immunodeficiency/genetics/*immunology ; X Chromosome
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  • 90
    Publication Date: 1993-12-10
    Description: Cytosine methylation has been implicated in epigenetic control of gene expression in animals, plants, and fungi. It has been assumed that all methylation in eukaryotes is at symmetrical sequences such as CpG/GpC, because this can explain perpetuation of methylation states. Here the bisulfite genomic sequencing method was used to examine methylation in DNA from a Neurospora gene exposed to repeat-induced point mutation. 5-Methylcytosine was not limited to symmetrical sites and individual molecules showed different patterns and amounts of modification. The methylation extended beyond the mutated region and even beyond the edge of the duplicated segment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Selker, E U -- Fritz, D Y -- Singer, M J -- GM 35690/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 10;262(5140):1724-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biology, University of Oregon, Eugene 97403.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8259516" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine ; Base Sequence ; Blotting, Southern ; Cytosine/*analogs & derivatives/analysis ; DNA Restriction Enzymes ; DNA, Fungal/chemistry/*metabolism ; DNA-Binding Proteins/genetics ; Fungal Proteins/genetics ; Genes, Fungal ; Glutamate Dehydrogenase/*genetics ; Methylation ; Molecular Sequence Data ; Neurospora crassa/enzymology/*genetics ; Point Mutation
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-09-03
    Description: Neocarzinostatin chromophore (NCS chrom) was found to induce site-specific cleavage at the 3' side of a bulge in single-stranded DNA in the absence of thiol. This reaction involved the oxidative formation of a DNA fragment with a nucleoside 5'-aldehyde at its 5' terminus and generated an ultraviolet light-absorbing and fluorescent species of post-activated drug containing tritium abstracted from the carbon at the 5' position of the target nucleotide. The DNAs containing point mutations that disrupt the bulge were not cleavage substrates and did not generate this drug product. Thus, DNA is an active participant in its own destruction, and NCS chrom may be useful as a probe for bulged structures in nucleic acids.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kappen, L S -- Goldberg, I H -- CA44257/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 3;261(5126):1319-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8362243" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Biotransformation ; *DNA Damage ; DNA, Single-Stranded/chemistry/*drug effects/genetics/metabolism ; Enediynes ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oxidation-Reduction ; Piperidines/pharmacology ; Point Mutation ; Sulfhydryl Compounds/pharmacology ; Zinostatin/*analogs & derivatives/chemistry/metabolism/pharmacology
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-07-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Culotta, E -- New York, N.Y. -- Science. 1993 Jul 2;261(5117):30-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8316854" target="_blank"〉PubMed〈/a〉
    Keywords: *Animal Communication ; Animals ; *Behavior, Animal ; Female ; Homing Behavior ; Male ; *Strepsirhini ; Vocalization, Animal
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, A -- New York, N.Y. -- Science. 1993 Aug 20;261(5124):987-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8351524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal ; *Biological Evolution ; Child ; *Child Abuse ; Female ; *Homicide ; Humans ; Male ; *Parents ; *Warfare
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  • 94
    Publication Date: 1993-03-05
    Description: The actions of many hormones and neurotransmitters are mediated by the members of a superfamily of receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins). These receptors are characterized by a highly conserved topographical arrangement in which seven transmembrane domains are connected by intracellular and extracellular loops. The interaction between these receptors and G proteins is mediated in large part by the third intracellular loop of the receptor. Coexpression of the third intracellular loop of the alpha 1B-adrenergic receptor with its parent receptor inhibited receptor-mediated activation of phospholipase C. The inhibition extended to the closely related alpha 1C-adrenergic receptor subtype, but not the phospholipase C-coupled M1 muscarinic acetylcholine receptor nor the adenylate cyclase-coupled D1A dopamine receptor. These results suggest that the receptor-G protein interface may represent a target for receptor antagonist drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Luttrell, L M -- Ostrowski, J -- Cotecchia, S -- Kendall, H -- Lefkowitz, R J -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Mar 5;259(5100):1453-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8383880" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Line ; Cloning, Molecular ; Cyclic AMP/metabolism ; Cytoplasm/metabolism ; GTP-Binding Proteins/*metabolism ; Globins/genetics ; Glutathione Transferase/genetics/metabolism ; Humans ; Inositol Phosphates/metabolism ; Kinetics ; Molecular Sequence Data ; Muscarinic Antagonists ; Oligodeoxyribonucleotides ; Plasmids ; Protein Structure, Secondary ; Receptors, Adrenergic, alpha/genetics/*metabolism ; Receptors, Dopamine D1/antagonists & inhibitors/genetics/*metabolism ; Receptors, Muscarinic/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism ; *Signal Transduction ; Transfection ; Type C Phospholipases/metabolism
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gibbons, A -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):680-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8342035" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brazil/epidemiology ; Disease Vectors ; Ecology ; Epidemiologic Methods ; Female ; Humans ; Infection/*epidemiology/transmission ; Male ; Papua New Guinea/epidemiology ; *Trees ; Tropical Medicine
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  • 96
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-06
    Description: Metalloenzymes effect a variety of important chemical transformations, often involving small molecule substrates or products such as molecular oxygen, hydrogen, nitrogen, and water. A diverse array of ions or metal clusters is observed at the active-site cores, but living systems use basic recurring structures that have been modified or tuned for specific purposes. Inorganic chemists are actively involved in the elucidation of the structure, spectroscopy, and mechanism of action of these biological catalysts, in part through a synthetic modeling approach involving biomimetic studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlin, K D -- GM28962/GM/NIGMS NIH HHS/ -- GM45971/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Aug 6;261(5122):701-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7688141" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/chemistry/metabolism ; Binding Sites ; Electron Transport ; Enzymes/*chemistry/metabolism ; Hydrolysis ; Iron-Sulfur Proteins/chemistry/metabolism ; Metalloproteins/*chemistry/metabolism ; *Models, Chemical ; Models, Molecular ; Nitric Oxide/metabolism ; Nitric Oxide Synthase ; Oxidation-Reduction ; Peptides/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 1993-05-07
    Description: Previously known 5' exonucleases of several eubacterial DNA polymerases have now been shown to be structure-specific endonucleases that cleave single-stranded DNA or RNA at the bifurcated end of a base-paired duplex. Cleavage was not coupled to synthesis, although primers accelerated the rate of cleavage considerably. The enzyme appeared to gain access to the cleavage site by moving from the free end of a 5' extension to the bifurcation of the duplex, where cleavage took place. Single-stranded 5' arms up to 200 nucleotides long were cleaved from such a duplex. Essentially any linear single-stranded nucleic acid can be targeted for specific cleavage by the 5' nuclease of DNA polymerase through hybridization with an oligonucleotide that converts the desired cleavage site into a substrate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyamichev, V -- Brow, M A -- Dahlberg, J E -- 30220/PHS HHS/ -- New York, N.Y. -- Science. 1993 May 7;260(5109):778-83.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biomolecular Chemistry, University of Wisconsin School of Medicine, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7683443" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; DNA, Single-Stranded/*metabolism ; DNA-Directed DNA Polymerase/*metabolism ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/*metabolism ; RNA/*metabolism ; Taq Polymerase ; Templates, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 1993-09-10
    Description: Interferons (IFNs) induce antiviral activity in many cell types. The ability of IFN-gamma to inhibit replication of ectromelia, vaccinia, and herpes simplex-1 viruses in mouse macrophages correlated with the cells' production of nitric oxide (NO). Viral replication was restored in IFN-gamma-treated macrophages exposed to inhibitors of NO synthase. Conversely, epithelial cells with no detectable NO synthesis restricted viral replication when transfected with a complementary DNA encoding inducible NO synthase or treated with organic compounds that generate NO. In mice, an inhibitor of NO synthase converted resolving ectromelia virus infection into fulminant mousepox. Thus, induction of NO synthase can be necessary and sufficient for a substantial antiviral effect of IFN-gamma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karupiah, G -- Xie, Q W -- Buller, R M -- Nathan, C -- Duarte, C -- MacMicking, J D -- CA43610/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1445-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7690156" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Oxidoreductases/*biosynthesis/metabolism ; Animals ; Arginine/analogs & derivatives/pharmacology ; Cell Line ; Cells, Cultured ; Ectromelia virus/drug effects/*physiology ; Ectromelia, Infectious/microbiology ; Enzyme Induction ; Female ; Humans ; Interferon-gamma/*pharmacology ; Macrophages/*microbiology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism/pharmacology ; Nitric Oxide Synthase ; Simplexvirus/drug effects/physiology ; Transfection ; Vaccinia virus/drug effects/physiology ; *Virus Replication/drug effects ; omega-N-Methylarginine
    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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  • 99
    Publication Date: 1993-08-27
    Description: In adult animals, template-independent (or N) nucleotides are frequently added during the rearrangement of variable (V), diversity (D), and joining (J) segments of lymphocyte receptor genes, greatly enhancing junctional diversity. Receptor genes from adult mice carrying a mutation in the terminal deoxynucleotidyl transferase (TdT) gene have few N nucleotides, providing proof that this enzyme is essential for creating diversity. Unlike those from normal adults, receptor genes from adult mutant mice show extensive evidence of homology-directed recombination, suggesting that TdT blocks this process. Thus, switch-on of the TdT gene during the first week after birth provokes an even greater expansion of lymphocyte receptor diversity than had previously been thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gilfillan, S -- Dierich, A -- Lemeur, M -- Benoist, C -- Mathis, D -- New York, N.Y. -- Science. 1993 Aug 27;261(5125):1175-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8356452" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; DNA Nucleotidylexotransferase/genetics/*metabolism ; Gene Rearrangement, B-Lymphocyte ; Gene Rearrangement, T-Lymphocyte ; *Genes, Immunoglobulin ; Immunoglobulin Joining Region/genetics ; Immunoglobulin Variable Region/genetics ; Lymphocytes/*immunology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; Nucleotides/*metabolism ; Receptors, Antigen, T-Cell/*genetics ; Recombination, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1993-10-15
    Description: Unlike most serine proteases of the chymotrypsin family, tissue-type plasminogen activator (tPA) is secreted from cells as an active, single-chain enzyme with a catalytic efficiency only slightly lower than that of the proteolytically cleaved form. A zymogenic mutant of tPA has been engineered that displays a reduction in catalytic efficiency by a factor of 141 in the single-chain form while retaining full activity in the cleaved form. The residues introduced in the mutant, serine 292 and histidine 305, are proposed to form a hydrogen-bonded network with aspartate 477, similar to the aspartate 194-histidine 40-serine 32 network found to stabilize the zymogen chymotrypsinogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Madison, E L -- Kobe, A -- Gething, M J -- Sambrook, J F -- Goldsmith, E J -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):419-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211162" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Aspartic Acid/chemistry ; Base Sequence ; Catalysis ; Chymotrypsin/chemistry/metabolism ; Enzyme Precursors/chemistry/*metabolism ; Histidine/chemistry ; Hydrogen Bonding ; Kinetics ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Plasminogen/metabolism ; Plasminogen Activator Inhibitor 1/metabolism ; Serine/chemistry ; Tissue Plasminogen Activator/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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