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  • Male  (228)
  • Kinetics  (58)
  • American Association for the Advancement of Science (AAAS)  (283)
  • Annual Reviews
  • 1990-1994  (140)
  • 1980-1984  (143)
  • 1993  (140)
  • 1984  (143)
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  • 1990-1994  (140)
  • 1980-1984  (143)
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  • 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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  • 2
    Publication Date: 1993-01-01
    Description: A myelin-associated protein from the central nervous system, the neurite growth inhibitor NI-35, inhibits regeneration of lesioned neuronal fiber tracts in vivo and growth of neurites in vitro. Growth cones of cultured rat dorsal root ganglion neurons arrested their growth and collapsed when exposed to liposomes containing NI-35. Before morphological changes, the concentration of free intracellular calcium ([Ca2+]i) showed a rapid and large increase in growth cones exposed to liposomes containing NI-35. Neither an increase in [Ca2+]i nor collapse of growth cones was detected in the presence of antibodies to NI-35. Dantrolene, an inhibitor of calcium release from caffeine-sensitive intracellular calcium stores, protected growth cones from collapse evoked by NI-35. Depletion of these caffeine-sensitive intracellular calcium stores prevented the increase in [Ca2+]i evoked by NI-35. The NI-35-evoked cascade of intracellular messengers that mediates collapse of growth cones includes the crucial step of calcium release from intracellular stores.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bandtlow, C E -- Schmidt, M F -- Hassinger, T D -- Schwab, M E -- Kater, S B -- NS24683/NS/NINDS NIH HHS/ -- NS28323/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):80-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Research Institute, University of Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418499" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caffeine/pharmacology ; Calcium/*metabolism ; Cells, Cultured ; Drug Carriers ; Fura-2 ; Ganglia, Spinal/*physiology ; Growth Inhibitors/*pharmacology ; Kinetics ; Liposomes ; Nerve Fibers/drug effects/*physiology/ultrastructure ; Neurons/drug effects/*physiology/ultrastructure ; Rats
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  • 3
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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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  • 4
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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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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-14
    Description: The perception of shape is independent of the size and position of the shape and also of the visual cue that defines it. The same shape can be recognized whether defined by a difference in luminance, by motion, or by texture. Experiments showed that the shape selectivity of individual cells in the macaque inferior temporal cortex did not vary with the size and position of a shape and also did not vary with the visual cue used to define the shape. This cue invariance was true for static luminance and texture cues as well as for relative motion cues--that is, for cues that are processed in ventral and dorsal visual pathways. The properties of these inferior temporal cells meet the demands of cue-invariant shape coding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sary, G -- Vogels, R -- Orban, G A -- New York, N.Y. -- Science. 1993 May 14;260(5110):995-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratorium voor Neuro- en Psychofysiologie, Faculteit der Geneeskunde, Katholieke Universiteit Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493538" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Form Perception ; Light ; Macaca mulatta ; Male ; Movement ; Neurons/*physiology ; Temporal Lobe/*physiology
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  • 6
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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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  • 7
    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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  • 8
    Publication Date: 1993-03-12
    Description: Glucagon and the glucagon receptor are a primary source of control over blood glucose concentrations and are especially important to studies of diabetes in which the loss of control over blood glucose concentrations clinically defines the disease. A complementary DNA clone for the glucagon receptor was isolated by an expression cloning strategy, and the receptor protein was expressed in several kidney cell lines. The cloned receptor bound glucagon and caused an increase in the intracellular concentration of adenosine 3', 5'-monophosphate (cAMP). The cloned glucagon receptor also transduced a signal that led to an increased concentration of intracellular calcium. The glucagon receptor is similar to the calcitonin and parathyroid hormone receptors. It can transduce signals leading to the accumulation of two different second messengers, cAMP and calcium.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jelinek, L J -- Lok, S -- Rosenberg, G B -- Smith, R A -- Grant, F J -- Biggs, S -- Bensch, P A -- Kuijper, J L -- Sheppard, P O -- Sprecher, C A -- New York, N.Y. -- Science. 1993 Mar 12;259(5101):1614-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ZymoGenetics Inc., Seattle, WA 98105.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8384375" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Calcium/pharmacology ; Cell Line ; Cloning, Molecular ; Cricetinae ; Cyclic AMP/metabolism ; Glucagon/metabolism/*pharmacology ; Kidney ; Kinetics ; Liver/*metabolism ; Molecular Sequence Data ; Rats ; Receptors, Gastrointestinal Hormone/genetics/metabolism/*physiology ; Receptors, Glucagon ; *Signal Transduction ; Transfection
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  • 9
    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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  • 10
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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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  • 11
    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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  • 12
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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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  • 13
    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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  • 14
    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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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-18
    Description: During the transition from embryonic to adult skeletal muscle, a decreased mean channel open time and accelerated desensitization of nicotinic acetylcholine (ACh) receptors result from the substitution of an epsilon subunit for gamma. A single ACh receptor channel of the embryonic type, expressed in Xenopus oocytes, interconverts between gating modes of short and long open time, whereas the adult receptor channel resides almost exclusively in the gating mode with short open time. Differences in the fraction of time spent in either gating mode account for the subunit dependence of both receptor open time and desensitization. Therefore, developmental changes in the kinetics of muscle ACh receptors may be imparted through subunit-dependent stabilization of intrinsic gating modes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naranjo, D -- Brehm, P -- NS18205/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1811-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8511590" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/*pharmacology ; Animals ; Embryo, Nonmammalian ; *Ion Channel Gating ; Kinetics ; Oocytes ; Receptors, Cholinergic/*metabolism ; Xenopus
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  • 16
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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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  • 17
    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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  • 18
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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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  • 19
    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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  • 20
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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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  • 21
    Publication Date: 1993-03-05
    Description: The binding and hydrolysis of guanosine triphosphate (GTP) by the small GTP-binding protein Sar1p is required to form transport vesicles from the endoplasmic reticulum (ER) in Saccharomyces cerevisiae. Experiments revealed that an interaction between Sar1p and the Sec23p subunit of an oligomeric protein is also required for vesicle budding. The isolated Sec23p subunit and the oligomeric complex stimulated guanosine triphosphatase (GTPase) activity of Sar1p 10- to 15-fold but did not activate two other small GTP-binding proteins involved in vesicle traffic (Ypt1p and ARF). Activation of GTPase was inhibited by an antibody to Sec23p but not by an antibody that inhibits the budding activity of the other subunit of the Sec23p complex. Also, activation was thermolabile in pure samples of Sec23p that were isolated from two independent sec23 mutant strains. It appears that Sec23p represents a new class of GTPase-activating protein because its sequence shows no similarity to any known member of this family.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshihisa, T -- Barlowe, C -- Schekman, R -- New York, N.Y. -- Science. 1993 Mar 5;259(5100):1466-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, 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/8451644" target="_blank"〉PubMed〈/a〉
    Keywords: COP-Coated Vesicles ; Cloning, Molecular ; Endoplasmic Reticulum/*metabolism/ultrastructure ; Fungal Proteins/genetics/metabolism ; GTP-Binding Proteins/genetics/*metabolism ; GTPase-Activating Proteins ; Genes, Fungal ; Kinetics ; Macromolecular Substances ; *Monomeric GTP-Binding Proteins ; Mutagenesis ; Proteins/*metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; *Saccharomyces cerevisiae Proteins ; Spheroplasts/metabolism ; Vesicular Transport Proteins
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  • 22
    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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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-11
    Description: Hippocampal long-term potentiation (LTP) is thought to serve as an elementary mechanism for the establishment of certain forms of explicit memory in the mammalian brain. As is the case with behavioral memory, LTP in the CA1 region has stages: a short-term early potentiation lasting 1 to 3 hours, which is independent of protein synthesis, precedes a later, longer lasting stage (L-LTP), which requires protein synthesis. Inhibitors of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) blocked L-LTP, and analogs of cAMP induced a potentiation that blocked naturally induced L-LTP. The action of the cAMP analog was blocked by inhibitors of protein synthesis. Thus, activation of PKA may be a component of the mechanism that generates L-LTP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frey, U -- Huang, Y Y -- Kandel, E R -- GM32099/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 11;260(5114):1661-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurobiology and Behavior, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8389057" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects/physiology ; Animals ; Cyclic AMP/*physiology ; Hippocampus/cytology/drug effects/*physiology ; In Vitro Techniques ; Male ; Memory/physiology ; Neurons/drug effects/*physiology ; Protein Kinases/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/physiology ; Second Messenger Systems/physiology ; Time Factors
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  • 24
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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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  • 25
    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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  • 26
    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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  • 27
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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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  • 28
    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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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-01
    Description: In humans temporal lobe epilepsy (TLE) is characterized by recurrent seizures, neuronal hyperexcitability, and selective loss of certain neuronal populations in the hippocampus. Animal models of the condition indicate that a diminution of inhibition mediated by gamma-aminobutyric acid (GABA) accounts for the altered function, and it has been hypothesized that the diminution arises because GABAergic basket interneurons are "dormant" as a result of their being disconnected from excitatory inputs. In hippocampal slices, inhibitory postsynaptic potentials (IPSPs) were elicited in CA1 pyramidal cells by activation of basket cells; responses from an animal model of TLE were compared to those from control tissue. IPSPs evoked indirectly by activation of terminals that then excited basket cells were reduced in the epileptic tissue, whereas IPSPs evoked by direct activation of basket cells, when excitatory neurotransmission was blocked, were not different from controls. These results provide support for the "dormant basket cell" hypothesis and have implications for the pathophysiology and treatment of human TLE.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bekenstein, J W -- Lothman, E W -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):97-100.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8093417" target="_blank"〉PubMed〈/a〉
    Keywords: 6-Cyano-7-nitroquinoxaline-2,3-dione ; Action Potentials ; Animals ; Baclofen/analogs & derivatives/pharmacology ; Electric Stimulation ; Epilepsy, Temporal Lobe/*physiopathology ; Evoked Potentials ; Hippocampus/*physiology/*physiopathology ; In Vitro Techniques ; Interneurons/drug effects/*physiology ; Male ; Membrane Potentials ; Picrotoxin/pharmacology ; Pyramidal Tracts/drug effects/*physiology ; Quinoxalines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A/physiology ; Receptors, N-Methyl-D-Aspartate/physiology ; Status Epilepticus/*physiopathology
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  • 30
    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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  • 31
    Publication Date: 1993-09-17
    Description: Staphylococcal nuclease is an enzyme with enormous catalytic power, accelerating phosphodiester bond hydrolysis by a factor of 10(16) over the spontaneous rate. The mechanistic basis for this rate acceleration was investigated by substitution of the active site residues Glu43, Arg35, and Arg87 with unnatural amino acid analogs. Two Glu43 mutants, one containing the nitro analog of glutamate and the other containing homoglutamate, retained high catalytic activity at pH 9.9, but were less active than the wild-type enzyme at lower pH values. The x-ray crystal structure of the homoglutamate mutant revealed that the carboxylate side chain of this residue occupies a position and orientation similar to that of Glu43 in the wild-type enzyme. The increase in steric bulk is accommodated by a backbone shift and altered torsion angles. The nitro and the homoglutamate mutants display similar pH versus rate profiles, which differ from that of the wild-type enzyme. Taken together, these studies suggest that Glu43 may not act as a general base, as previously thought, but may play a more complex structural role during catalysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Judice, J K -- Gamble, T R -- Murphy, E C -- de Vos, A M -- Schultz, P G -- GM 14012-02S1/GM/NIGMS NIH HHS/ -- R01 GM49220/GM/NIGMS NIH HHS/ -- T32GM-08388/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 17;261(5128):1578-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8103944" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Aminoadipic Acid/chemistry ; Amino Acids/chemistry ; Aminobutyrates/chemistry ; Arginine/*chemistry ; Binding Sites ; Catalysis ; Glutamates/*chemistry ; Glutamic Acid ; Homocysteine/analogs & derivatives/chemistry ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Kinetics ; Micrococcal Nuclease/chemistry/genetics/*metabolism ; Mutation ; Plasmids ; X-Ray Diffraction
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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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  • 33
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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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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-22
    Description: Neurotransmitters acting on presynaptic terminals regulate synaptic transmission and plasticity. Because of the difficulty of direct electrophysiological recording from small presynaptic terminals, little is known about the ion channels that mediate these actions or about the mechanisms by which transmitter secretion is altered. The patch-clamp technique is used to show that the predominant inhibitory presynaptic neurotransmitter, gamma-aminobutyric acid (GABA), activates a GABAA receptor and gates a chloride channel in the membranes of peptidergic nerve terminals of the posterior pituitary. The opening of a chloride channel by GABA weakly depolarizes the nerve terminal membrane and blocks action potentials. In this way, GABA limits secretion by retarding the spread of excitation into the terminal arborization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, S J -- Jackson, M B -- NS30016/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):531-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Wisconsin Medical School, Madison 53706.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8380942" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bicuculline/pharmacology ; Chlordiazepoxide/pharmacology ; Chloride Channels ; Chlorides/*metabolism ; GABA-A Receptor Antagonists ; Male ; Membrane Potentials/drug effects ; Membrane Proteins/drug effects/*physiology ; Muscimol/pharmacology ; Nerve Endings/drug effects/*physiology ; Picrotoxin/pharmacology ; Pituitary Gland, Posterior/drug effects/*physiology ; Rats ; Receptors, GABA-A/*physiology ; gamma-Aminobutyric Acid/*pharmacology
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  • 35
    Publication Date: 1993-02-26
    Description: Attempts to correlate behavioral learning with cellular changes, such as increased synaptic efficacy, have often relied on increased extracellular potentials as an index of enhanced synaptic strength. A recent example is the enlarged excitatory field potentials in the dentate gyrus of rats that are learning spatial relations by exploration. The altered hippocampal field potentials do not reflect learning-specific cellular changes but result from a concomitant rise in brain temperature that is caused by the associated muscular effort. Enhanced dentate field excitatory potentials followed both passive and active heating and were linearly related to the brain temperature. These temperature-related effects may mask any learning-induced changes in field potential.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moser, E -- Mathiesen, I -- Andersen, P -- New York, N.Y. -- Science. 1993 Feb 26;259(5099):1324-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurophysiology, University of Oslo, Norway.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8446900" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology ; Body Temperature ; Cerebellar Nuclei/*physiology ; Hippocampus/*physiology ; Male ; Membrane Potentials ; Physical Exertion ; Rats ; Swimming/physiology
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-11-26
    Description: Protein phosphatases play important roles in the regulation of cell growth and metabolism, yet little is known about their enzymatic mechanism. By extrapolation from data on inhibitors of other types of hydrolases, an inhibitor of prostatic acid phosphatase was designed that is likely to function as a mechanism-based phosphotyrosine phosphatase inactivator. This molecule, 4-(fluoromethyl)phenyl phosphate, represents a useful paradigm for the design of potent and specific phosphatase inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Myers, J K -- Widlanski, T S -- R01 GM47918-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Nov 26;262(5138):1451-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Indiana University, Bloomington 47405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8248785" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Phosphatase/*antagonists & inhibitors/metabolism ; Alkylation ; Binding Sites ; Drug Design ; Humans ; Hydrolysis ; Kinetics ; Male ; Organophosphorus Compounds/metabolism/*pharmacology ; Prostate/*enzymology
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  • 37
    Publication Date: 1993-06-25
    Description: Nitric oxide (NO) and carbon monoxide (CO) may act as retrograde messages for long-term potentiation (LTP) in the hippocampus. Zinc protoporphyrin IX, an inhibitor of the enzyme that produces CO, blocked induction of LTP in the CA1 region of hippocampal slices. Application of either NO or CO to slices produced a rapid and long-lasting increase in the size of evoked synaptic potentials if, and only if, the application occurred at the same time as weak tetanic stimulation. This long-term enhancement was spatially restricted to synapses from active presynaptic fibers and appeared to involve mechanisms utilized by LTP, occluding the subsequent induction of LTP by strong tetanic stimulation. The enhancement by NO and CO was not blocked by an N-methyl-D-aspartate (NMDA) receptor blocker, suggesting that NO and CO act downstream from the NMDA receptor. Also, CO produced long-term enhancement when paired with low-frequency stimulation. These results are consistent with the hypothesis that NO and CO, either alone or in combination, serve as retrograde messages that produce activity-dependent presynaptic enhancement during LTP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhuo, M -- Small, S A -- Kandel, E R -- Hawkins, R D -- AG08702/AG/NIA NIH HHS/ -- MH45923/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 25;260(5116):1946-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8100368" target="_blank"〉PubMed〈/a〉
    Keywords: 6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Carbon Monoxide/*pharmacology ; Electric Stimulation ; Guinea Pigs ; Hippocampus/drug effects/*physiology ; In Vitro Techniques ; Male ; Membrane Potentials/drug effects ; Nitric Oxide/*pharmacology ; Protoporphyrins/pharmacology ; Quinoxalines/pharmacology ; Signal Transduction/drug effects ; Synapses/drug effects/*physiology
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  • 38
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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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  • 39
    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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  • 40
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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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  • 41
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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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  • 42
    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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  • 43
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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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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Curtis, T -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418488" target="_blank"〉PubMed〈/a〉
    Keywords: *AIDS Vaccines ; Acquired Immunodeficiency Syndrome/immunology/*transmission ; Animals ; Cells, Cultured ; *Hiv-1 ; Haplorhini ; Humans ; Kidney ; Male
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  • 45
    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
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-04-30
    Description: Cardiac hypertrophy in response to systolic pressure loading frequently results in contractile dysfunction of unknown cause. In the present study, pressure loading increased the microtubule component of the cardiac muscle cell cytoskeleton, which was responsible for the cellular contractile dysfunction observed. The linked microtubule and contractile abnormalities were persistent and thus may have significance for the deterioration of initially compensatory cardiac hypertrophy into congestive heart failure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsutsui, H -- Ishihara, K -- Cooper, G 4th -- HL37196/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 30;260(5108):682-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Medical University of South Carolina, Charleston.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8097594" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/drug effects/physiology ; Animals ; Cardiomegaly/pathology/*physiopathology ; Cats ; Colchicine/pharmacology ; Cytochalasin D/pharmacology ; Desmin/physiology ; Female ; Heart Septal Defects, Atrial/physiopathology ; Intermediate Filaments/drug effects/physiology ; Male ; Microtubules/drug effects/pathology/*physiology ; *Myocardial Contraction ; Myocardium/*pathology ; Paclitaxel/pharmacology ; Pressure ; Sarcomeres/drug effects/physiology ; Ventricular Function, Right
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-17
    Description: Most members of the guanosine triphosphatase (GTPase) superfamily hydrolyze guanosine triphosphate (GTP) quite slowly unless stimulated by a GTPase activating protein or GAP. The alpha subunits (G alpha) of the heterotrimeric G proteins hydrolyze GTP much more rapidly and contain an approximately 120-residue insert not found in other GTPases. Interactions between a G alpha insert domain and a G alpha GTP-binding core domain, both expressed as recombinant proteins, show that the insert acts biochemically as a GAP. The results suggest a general mechanism for GAP-dependent hydrolysis of GTP by other GTPases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Markby, D W -- Onrust, R -- Bourne, H R -- 5F32-GM13918/GM/NIGMS NIH HHS/ -- CA54427/CA/NCI NIH HHS/ -- GM27800/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 17;262(5141):1895-901.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmcology, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266082" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Colforsin/pharmacology ; Cyclic AMP/metabolism ; GTP Phosphohydrolases/*metabolism ; GTP-Binding Proteins/chemistry/*metabolism ; Guanosine 5'-O-(3-Thiotriphosphate)/metabolism/pharmacology ; Guanosine Triphosphate/*metabolism ; Hydrolysis ; Kinetics ; Molecular Sequence Data ; Mutation ; Protein Conformation
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  • 48
    Publication Date: 1993-06-18
    Description: Cytoplasmic incompatibility (CI) in Drosophila simulans is related to infection of the germ line by a rickettsial endosymbiont (genus Wolbachia). Wolbachia were transferred by microinjection of egg cytoplasm into uninfected eggs of both D. simulans and D. melanogaster to generate infected populations. Transinfected strains of D. melanogaster with lower densities of Wolbachia than the naturally infected D. simulans strain did not express high levels of CI. However, transinfected D. melanogaster egg cytoplasm, transferred back into D. simulans, generated infected populations that expressed CI at levels near those of the naturally infected strain. A transinfected D. melanogaster line selected for increased levels of CI expression also displayed increased symbiont densities. These data suggest that a threshold level of infection is required for normal expression of CI and that host factors help determine the density of the symbiont in the host.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boyle, L -- O'Neill, S L -- Robertson, H M -- Karr, T L -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1796-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Illinois, Urbana 61801.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8511587" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytoplasm/microbiology/physiology ; Drosophila/*microbiology/physiology ; Drosophila melanogaster/*microbiology/physiology ; Female ; Male ; Microinjections ; Microscopy ; Ovum/microbiology/physiology ; Rickettsiaceae/*physiology
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-11-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, E -- New York, N.Y. -- Science. 1993 Nov 5;262(5135):832, 834-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bunyaviridae Infections/epidemiology/*microbiology/therapy/transmission ; Disease Outbreaks ; Disease Reservoirs ; Disease Vectors ; Female ; Genome, Viral ; Hantavirus/*genetics/isolation & purification/pathogenicity ; Humans ; Lung Diseases/epidemiology/*microbiology/therapy ; Male ; Peromyscus/microbiology ; *Polymerase Chain Reaction ; Rodent Control ; Southwestern United States/epidemiology ; United States/epidemiology
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  • 50
    Publication Date: 1993-10-08
    Description: Diaphragmatic function and intrapulmonary respiratory flow in running mammals were found to differ substantially from the corresponding conditions known in resting mammals. In trotting dogs, orbital oscillations of the diaphragm were driven by inertial displacements of the viscera induced by locomotion. In turn, oscillations of the visceral mass drove pulmonary ventilation independent of diaphragmatic contractions, which primarily served to modulate visceral kinetics. Visceral displacements and loading of the anterior chest wall by the forelimbs are among the factors that contribute to an asynchronous ventilation of the lungs and interlobar gas recycling. Basic features of mammalian respiratory design, including the structure of the diaphragm and lobation of the lungs, appear to reflect the mechanical requirements of locomotor-respiratory integration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bramble, D M -- Jenkins, F A Jr -- S07 RR07092/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 8;262(5131):235-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Utah, Salt Lake City 84112.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cineradiography ; Diaphragm/anatomy & histology/*physiology ; Dogs ; Female ; Locomotion/*physiology ; Lung/anatomy & histology/*physiology/radiography ; Male ; Models, Biological ; Muscle Contraction ; Radiography, Thoracic ; Respiratory Mechanics/*physiology
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  • 51
    Publication Date: 1993-09-24
    Description: Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trentham, D E -- Dynesius-Trentham, R A -- Orav, E J -- Combitchi, D -- Lorenzo, C -- Sewell, K L -- Hafler, D A -- Weiner, H L -- AG00294/AG/NIA NIH HHS/ -- MO1 RR01032/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 24;261(5129):1727-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Beth Israel Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8378772" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid/*drug therapy/immunology ; Autoimmune Diseases/*drug therapy/immunology ; Collagen/*administration & dosage/adverse effects/therapeutic use ; Double-Blind Method ; Female ; Humans ; Immune Tolerance ; Male ; Middle Aged ; Placebo Effect ; T-Lymphocytes/immunology
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-08-13
    Description: The role of major histocompatibility complex (MHC) molecules in T cell differentiation was investigated by comparison of thymocyte subpopulations in wild-type mice and beta 2-microglobulin (beta 2M) mutant mice deficient in MHC class I expression and mature CD8+ cells. On the basis of surface markers, glucocorticoid resistance, in vitro differentiation capacity, and absence in beta 2 M-l- mice, CD4intermediateCD8hi cells with high expression of alpha beta T cell receptor (TCR alpha beta) were identified as having been positively selected by MHC class I for development into mature CD8+ T cells. Activated CD4intCD8hi cells bearing intermediate rather than high amounts of TCR were present in both wild-type and beta 2M-l- animals. These data suggest that recognition of MHC class I molecules is required for full maturation to CD8+ T cells, but not for receptor-initiated commitment to the CD8+ lineage, consistent with a stochastic (selection) model of thymocyte development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Meerwijk, J P -- Germain, R N -- New York, N.Y. -- Science. 1993 Aug 13;261(5123):911-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Biology Section, 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/8102208" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/analysis ; Antigens, CD8/*analysis ; CD4-Positive T-Lymphocytes/cytology/immunology ; Cell Differentiation ; Dexamethasone/pharmacology ; Histocompatibility Antigens Class I/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Phenotype ; Receptors, Antigen, T-Cell, alpha-beta/*analysis ; T-Lymphocyte Subsets/cytology/drug effects/*immunology
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  • 53
    Publication Date: 1993-02-05
    Description: beta-Adrenergic receptor kinase (beta ARK) and beta-arrestin function in the homologous or agonist-activated desensitization of G protein-coupled receptors. The isoforms beta ARK-2 and beta-arrestin-2 are highly enriched in and localized to the dendritic knobs and cilia of the olfactory receptor neurons where the initial events of olfactory signal transduction occur. Odorants induce a rapid and transient elevation of adenosine 3',5'-monophosphate (cAMP), which activates a nonspecific cation channel and produces membrane depolarization. Preincubation of rat olfactory cilia with antibodies raised against beta ARK-2 and beta-arrestin-2 increased the odorant-induced elevation of cAMP and attenuated desensitization. These results suggest that beta ARK-2 and beta-arrestin-2 mediate agonist-dependent desensitization in olfaction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, T M -- Arriza, J L -- Jaworsky, D E -- Borisy, F F -- Attramadal, H -- Lefkowitz, R J -- Ronnett, G V -- NS 01578-01/NS/NINDS NIH HHS/ -- NS-02131/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 5;259(5096):825-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins Medical Institutions, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8381559" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/*metabolism ; *Arrestins ; Cells, Cultured ; Cyclic AMP/metabolism ; *Cyclic AMP-Dependent Protein Kinases ; Cytosol/metabolism ; Dendrites/physiology ; Eye Proteins/*metabolism ; G-Protein-Coupled Receptor Kinase 2 ; GTP-Binding Proteins/*metabolism ; Isoenzymes/metabolism ; Male ; Mechanoreceptors/*physiology ; Neurons/*physiology ; *Odors ; Olfactory Bulb/*physiology ; Protein Kinases/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/*physiology ; Signal Transduction ; *Smell ; Testis/physiology ; Turbinates/*physiology ; beta-Adrenergic Receptor Kinases
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  • 54
    Publication Date: 1993-05-21
    Description: The folding of the all-beta sheet protein, interleukin-1 beta, was studied with nuclear magnetic resonance (NMR) spectroscopy, circular dichroism, and fluorescence. Ninety percent of the beta structure present in the native protein, as monitored by far-ultraviolet circular dichroism, was attained within 25 milliseconds, correlating with the first kinetic phase determined by tryptophan and 1-anilinonaphthalene-8-sulfonate fluorescence. In contrast, formation of stable native secondary structure, as measured by quenched-flow deuterium-hydrogen exchange experiments, began after only 1 second. Results from the NMR experiments indicated the formation of at least two intermediates with half-lives of 0.7 to 1.5 and 15 to 25 seconds. The final stabilization of the secondary structure, however, occurs on a time scale much greater than 25 seconds. These results differ from previous results on mixed alpha helix-beta sheet proteins in which both the alpha helices and beta sheets were stabilized very rapidly (less than 10 to 20 milliseconds).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Varley, P -- Gronenborn, A M -- Christensen, H -- Wingfield, P T -- Pain, R H -- Clore, G M -- New York, N.Y. -- Science. 1993 May 21;260(5111):1110-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493553" target="_blank"〉PubMed〈/a〉
    Keywords: Circular Dichroism ; Hydrogen Bonding ; Interleukin-1/*chemistry ; Kinetics ; Magnetic Resonance Spectroscopy ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Spectrometry, Fluorescence
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  • 55
    Publication Date: 1993-06-25
    Description: Arrestins have been implicated in the regulation of many G protein-coupled receptor signaling cascades. Mutations in two Drosophila photoreceptor-specific arrestin genes, arrestin 1 and arrestin 2, were generated. Analysis of the light response in these mutants shows that the Arr1 and Arr2 proteins are mediators of rhodopsin inactivation and are essential for the termination of the phototransduction cascade in vivo. The saturation of arrestin function by an excess of activated rhodopsin is responsible for a continuously activated state of the photoreceptors known as the prolonged depolarized afterpotential. In the absence of arrestins, photoreceptors undergo light-dependent retinal degeneration as a result of the continued activity of the phototransduction cascade. These results demonstrate the fundamental requirement for members of the arrestin protein family in the regulation of G protein-coupled receptors and signaling cascades in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolph, P J -- Ranganathan, R -- Colley, N J -- Hardy, R W -- Socolich, M -- Zuker, C S -- R01 EY008768/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 25;260(5116):1910-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, La Jolla, CA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8316831" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; *Arrestins ; Drosophila ; Drosophila Proteins ; Eye Proteins/genetics/*physiology ; Female ; GTP-Binding Proteins/*metabolism ; Genes, Insect ; Kinetics ; Male ; Molecular Sequence Data ; Mutation ; Phosphoproteins/genetics/*physiology ; Photic Stimulation ; Photoreceptor Cells/cytology/*physiology ; Rhodopsin/analogs & derivatives/*metabolism
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  • 56
    Publication Date: 1993-05-07
    Description: Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peltomaki, P -- Aaltonen, L A -- Sistonen, P -- Pylkkanen, L -- Mecklin, J P -- Jarvinen, H -- Green, J S -- Jass, J R -- Weber, J L -- Leach, F S -- CA 35494/CA/NCI NIH HHS/ -- CA 47527/CA/NCI NIH HHS/ -- HG 00248/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1993 May 7;260(5109):810-2.〈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/8484120" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosome Mapping ; *Chromosomes, Human, Pair 2 ; Colonic Neoplasms/*genetics ; Colorectal Neoplasms/*genetics ; DNA, Satellite/genetics ; Disease Susceptibility ; Female ; *Genes ; Genetic Markers ; Humans ; Male ; Pedigree ; Rectal Neoplasms/genetics
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  • 57
    Publication Date: 1993-01-01
    Description: An introduced whitefly species, responsible for over a half billion dollars in damage to U.S. agricultural production in 1991, is morphologically indistinguishable from Bemisia tabaci (Gennadius). However, with the use of polymerase chain reaction-based DNA differentiation tests, allozymic frequency analyses, crossing experiments, and mating behavior studies, the introduced whitefly is found to be a distinct species. Recognition of this new species, the silverleaf whitefly, is critical in the search for management options.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perring, T M -- Cooper, A D -- Rodriguez, R J -- Farrar, C A -- Bellows, T S Jr -- New York, N.Y. -- Science. 1993 Jan 1;259(5091):74-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, University of California, Riverside 92521.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8418497" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; Crosses, Genetic ; DNA/genetics ; Diptera/*classification/genetics/*physiology ; Enzymes/genetics ; Female ; Genetic Linkage ; Male ; Molecular Sequence Data ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sexual Behavior, Animal ; United States
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  • 58
    Publication Date: 1993-06-04
    Description: Biological variability of human immunodeficiency virus type-1 (HIV-1) is involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Syncytium-inducing (SI) HIV-1 variants emerge in 50 percent of infected individuals during infection, preceding accelerated CD4+ T cell loss and rapid progression to AIDS. The V1 to V2 and V3 region of the viral envelope glycoprotein gp120 contained the major determinants of SI capacity. The configuration of a hypervariable locus in the V2 domain appeared to be predictive for non-SI to SI phenotype conversion. Early prediction of HIV-1 phenotype evolution may be useful for clinical monitoring and treatment of asymptomatic infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Groenink, M -- Fouchier, R A -- Broersen, S -- Baker, C H -- Koot, M -- van't Wout, A B -- Huisman, H G -- Miedema, F -- Tersmette, M -- Schuitemaker, H -- New York, N.Y. -- Science. 1993 Jun 4;260(5113):1513-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8502996" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/microbiology ; Amino Acid Sequence ; Base Sequence ; Biological Evolution ; Consensus Sequence ; Genetic Variation ; Giant Cells/microbiology ; HIV Envelope Protein gp120/*chemistry ; HIV Seropositivity/microbiology ; HIV-1/*chemistry/*genetics/pathogenicity ; Humans ; Male ; Molecular Sequence Data ; Phenotype ; Protein Conformation ; Recombination, Genetic
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  • 59
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 1993 Apr 30;260(5108):611.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8480171" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*prevention & control ; Counseling/*legislation & jurisprudence ; Financing, Government ; *Homosexuality ; Hotlines/*legislation & jurisprudence ; Humans ; Male ; National Institute of Mental Health (U.S.) ; United States
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-24
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poder, R -- New York, N.Y. -- Science. 1993 Dec 24;262(5142):1956.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8086009" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Freezing ; History, Ancient ; Hominidae/*microbiology ; Humans ; Male ; *Mummies ; Polyporaceae/*isolation & purification
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  • 61
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kingman, S -- New York, N.Y. -- Science. 1993 Oct 29;262(5134):648-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8235581" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Child ; Cluster Analysis ; England/epidemiology ; Fathers ; Humans ; Leukemia, Radiation-Induced/epidemiology ; Male ; Neoplasms, Radiation-Induced/*epidemiology ; *Nuclear Reactors ; *Occupational Exposure
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  • 62
    Publication Date: 1993-09-03
    Description: The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expressed on the surface of activated CD4+ T cells and is essential for thymus-dependent humoral immunity. The role of gp39-CD40 interactions in autoimmune disease was investigated in vivo with the use of an antibody that blocks their interactions (anti-gp39). Arthritis induced in mice by immunization with type II collagen was inhibited by anti-gp39. Anti-gp39 blocked the development of joint inflammation, serum antibody titers to collagen, the infiltration of inflammatory cells into the subsynovial tissue, and the erosion of cartilage and bone. Thus, interference with gp39-CD40 interactions may have therapeutic potential in the treatment of autoimmune disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Durie, F H -- Fava, R A -- Foy, T M -- Aruffo, A -- Ledbetter, J A -- Noelle, R J -- AI26296/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 3;261(5126):1328-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7689748" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/*immunology ; Antigens, CD/*immunology ; Antigens, CD40 ; Antigens, Differentiation, B-Lymphocyte/*immunology ; Antigens, Differentiation, T-Lymphocyte/*immunology ; Arthritis, Experimental/immunology/pathology/prevention & control ; Arthritis, Rheumatoid/immunology/pathology/*prevention & control ; Autoimmune Diseases/immunology/pathology/*prevention & control ; CD40 Ligand ; Collagen/immunology ; Disease Models, Animal ; Immunization ; Immunoglobulin G/blood ; Joints/pathology ; Ligands ; Male ; Membrane Glycoproteins/*immunology ; Mice ; Mice, Inbred DBA
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  • 63
    Publication Date: 1993-06-25
    Description: Type I diabetes is an autoimmune disease involving an interaction between an epigenetic event (possibly a viral infection), the pancreatic beta cells, and the immune system in a genetically susceptible host. The possibility that the type I interferons could mediate this interaction was tested with transgenic mice in which the insulin-producing beta cells expressed an interferon-alpha. These mice developed a hypoinsulinemic diabetes associated with a mixed inflammation centered on the islets. The inflammation and the diabetes were prevented with a neutralizing antibody to the interferon-alpha. Thus, the expression of interferon-alpha by the beta cells could be causal in the development of type I diabetes, which suggests a therapeutic approach to this disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stewart, T A -- Hultgren, B -- Huang, X -- Pitts-Meek, S -- Hully, J -- MacLachlan, N J -- New York, N.Y. -- Science. 1993 Jun 25;260(5116):1942-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Endocrine Research, Genentech, Inc., South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8100367" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/therapeutic use ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; Diabetes Mellitus, Type 1/*etiology/immunology/pathology ; Female ; Glucagon/analysis ; Insulin/analysis/blood ; Interferon-alpha/*biosynthesis/immunology ; Islets of Langerhans/immunology/*metabolism/pathology ; Leukocytes, Mononuclear ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neutralization Tests ; Somatostatin/analysis
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-12-10
    Description: A fundamental question about cognition concerns how knowledge about a category is acquired through encounters with examples of the category. Amnesic patients and control subjects performed similarly at classifying novel patterns according to whether they belonged to the same category as a set of training patterns. In contrast, the amnesic patients were impaired at recognizing which dot patterns had been presented for training. Category learning appears to be independent of declarative (explicit) memory for training instances and independent of the brain structures essential for declarative memory that are damaged in amnesia. Knowledge about categories can be acquired implicitly by cumulating information from multiple examples.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knowlton, B J -- Squire, L R -- MH24600/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 1993 Dec 10;262(5140):1747-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Veterans Affairs Medical Center, San Diego, CA 92161.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8259522" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Amnesia/*psychology ; Female ; Humans ; *Learning ; Male ; *Memory ; Middle Aged
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  • 65
    Publication Date: 1993-09-17
    Description: The CD8 alpha cytoplasmic domain associates with p56lck, a nonreceptor protein-tyrosine kinase. The biological relevance of CD8 alpha-Lck association in T cell development was tested with transgenic mice generated to express a CD8 alpha molecule with two amino acid substitutions in its cytoplasmic domain, which abolishes the association of CD8 alpha with Lck. The CD8 alpha mutant was analyzed in a CD8-/- background and in the context of the transgenic 2C T cell receptor. The development and function of CD8+ T cells in these mice were apparently normal. Thus, CD8 alpha-Lck association is not necessary for positive selection, negative selection, or CD8-dependent cytotoxic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, I T -- Limmer, A -- Louie, M C -- Bullock, E D -- Fung-Leung, W P -- Mak, T W -- Loh, D Y -- AI 155322-13/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 17;261(5128):1581-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, Genetics, and Molecular Microbiology, 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/8372352" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD4/metabolism ; Antigens, CD8/immunology/*metabolism ; *Cytotoxicity, Immunologic ; Female ; Genes, MHC Class I ; Lymphocyte Culture Test, Mixed ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation ; Phosphorylation ; Protein-Tyrosine Kinases/*metabolism ; Receptors, Antigen, T-Cell ; T-Lymphocytes, Cytotoxic/*immunology
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-01-22
    Description: Organic reactions are often limited by stereoelectronic constrains that appear along the reaction coordinate. An antibody has been generated that overcomes these constraints and catalyzes a highly disfavored chemical transformation. The antibody facilitates the difficult 6-endo-tet ring closure of an epoxy-alcohol to form a tetrahydropyran. The catalyzed process is in formal violation of what has become known as Baldwin's rules for ring-closure reactions. In addition to controlling the regiochemistry of the disfavored cyclization reaction, these catalytic antibodies resolve enantiomeric substrates to afford a stereochemically pure product. The principles demonstrated in this study may be applicable to other disfavored chemical processes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janda, K D -- Shevlin, C G -- Lerner, R A -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):490-3.〈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/8424171" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/*metabolism ; Catalysis ; Enzymes/metabolism ; Heterocyclic Compounds/*chemistry ; Indicators and Reagents ; Isomerism ; Kinetics
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  • 67
    Publication Date: 1993-07-16
    Description: Mice that bear the X-linked immunodeficiency (xid) mutation have a B lymphocyte-specific defect resulting in an inability to make antibody responses to polysaccharide antigens. A backcross of 1114 progeny revealed the colocalization of xid with Bruton's agammaglobulinemia tyrosine kinase (btk) gene, which is implicated in the human immune deficiency, X-linked agammaglobulinemia. Mice that carry xid have a missense mutation that alters a highly conserved arginine near the amino-terminus of the btk protein, Btk. Because this region of Btk lies outside any obvious kinase domain, the xid mutation may define another aspect of tyrosine kinase function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, J D -- Sideras, P -- Smith, C I -- Vorechovsky, I -- Chapman, V -- Paul, W E -- GM33160/GM/NIGMS NIH HHS/ -- HG00277/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jul 16;261(5119):355-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, 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/8332900" target="_blank"〉PubMed〈/a〉
    Keywords: Agammaglobulinemia/enzymology/*genetics/immunology ; Amino Acid Sequence ; Animals ; B-Lymphocytes/enzymology/immunology ; Base Sequence ; Chromosome Mapping ; Crosses, Genetic ; Female ; *Genes ; Genetic Linkage ; Immunologic Deficiency Syndromes/enzymology/*genetics/immunology ; Male ; Mice ; Mice, Inbred CBA ; Mice, Mutant Strains ; Molecular Sequence Data ; Muridae ; Mutation ; Protein-Tyrosine Kinases/chemistry/*genetics/metabolism ; *X Chromosome
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-09-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Benner, S A -- New York, N.Y. -- Science. 1993 Sep 10;261(5127):1402-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Organic Chemistry, Eidgenossisiche Technische Hochschule Zentrum, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8367723" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; DNA-Directed RNA Polymerases/metabolism ; Kinetics ; RNA Ligase (ATP)/chemistry/metabolism ; RNA, Catalytic/chemistry/*metabolism
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  • 69
    Publication Date: 1993-01-29
    Description: A proportion of developing oligodendrocytes undergo natural cell death by apoptosis, and mature oligodendrocytes die, either by apoptosis or necrosis, in response to injurious signals such as cytotoxic cytokines and complement. Ciliary neurotrophic factor (CNTF), a trophic factor found in astrocytes in the central nervous system (CNS), promoted the survival and maturation of cultured oligodendrocytes. This trophic factor also protected oligodendrocytes from death induced by tumor necrosis factors (apoptosis) but not against complement (necrosis). These results suggest that CNTF functions in the survival of oligodendrocytes during development and may lead to therapeutic approaches for degenerative diseases of the CNS that involve oligodendrocyte destruction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Louis, J C -- Magal, E -- Takayama, S -- Varon, S -- NS16349/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):689-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla 92093.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430320" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Astrocytes/physiology ; Cell Death/*drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Central Nervous System/physiology ; Ciliary Neurotrophic Factor ; Dose-Response Relationship, Drug ; Humans ; Kinetics ; Lymphotoxin-alpha/*pharmacology ; Nerve Growth Factors/*pharmacology ; Nerve Tissue Proteins/*pharmacology ; Oligodendroglia/cytology/drug effects/*physiology ; Recombinant Proteins/pharmacology ; Time Factors ; Tumor Necrosis Factor-alpha/*pharmacology
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  • 70
    Publication Date: 1993-10-22
    Description: The large subunit of the human pre-messenger RNA splicing factor U2 small nuclear ribonucleoprotein auxiliary factor (hU2AF65) is required for spliceosome assembly in vitro. A complementary DNA clone encoding the large subunit of Drosophila U2AF (dU2AF50) has been isolated. The dU2AF50 protein is closely related to its mammalian counterpart and contains three carboxyl-terminal ribonucleoprotein consensus sequence RNA binding domains and an amino-terminal arginine- and serine-rich (R/S) domain. Recombinant dU2AF50 protein complements mammalian splicing extracts depleted of U2AF activity. Germline transformation of Drosophila with the dU2AF50 complementary DNA rescues a lethal mutation, establishing that the dU2AF50 gene is essential for viability. R/S domains have been found in numerous metazoan splicing factors, but their function is unknown. The mutation in Drosophila U2AF will allow in vivo analysis of a conserved R/S domain-containing general splicing factor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kanaar, R -- Roche, S E -- Beall, E L -- Green, M R -- Rio, D C -- R01-HD28063/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 22;262(5133):569-73.〈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/7692602" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Conserved Sequence ; DNA, Complementary ; Drosophila melanogaster/*genetics/growth & development ; Female ; Gene Transfer Techniques ; Genes, Insect ; Genes, Lethal ; In Situ Hybridization ; Male ; Molecular Sequence Data ; Mutation ; *Nuclear Proteins ; RNA/metabolism ; RNA Precursors/*metabolism ; *RNA Splicing ; Recombinant Proteins/metabolism ; Ribonucleoproteins/chemistry/*genetics/metabolism ; Sequence Alignment
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  • 71
    Publication Date: 1993-01-15
    Description: Rab geranylgeranyl transferase (GG transferase) is a two-component enzyme that attaches 20-carbon isoprenoid groups to cysteine residues in Rab proteins, a family of guanosine triphosphate-binding proteins that regulate vesicular traffic. The mutant gene in human choroideremia, an X-linked form of retinal degeneration, encodes a protein that resembles component A of rat Rab GG transferase. Lymphoblasts from choroideremia subjects showed a marked deficiency in the activity of component A, but not component B, of Rab GG transferase. The deficiency was more pronounced when the substrate was Rab3A, a synaptic vesicle protein, than it was when the substrate was Rab1A, a protein of the endoplasmic reticulum. The data imply the existence of multiple component A proteins, one of which is missing in choroideremia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seabra, M C -- Brown, M S -- Goldstein, J L -- HL 20948/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 15;259(5093):377-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, 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/8380507" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Alkyl and Aryl Transferases ; Cell Line, Transformed ; Cells, Cultured ; Choroid/chemistry ; Choroideremia/*genetics ; Female ; GTP-Binding Proteins/analysis/*metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Lymphocyte Activation ; Male ; Middle Aged ; Mutation ; Nerve Tissue Proteins/analysis/*metabolism ; Photoreceptor Cells/chemistry ; Pigment Epithelium of Eye/chemistry ; Protein Prenylation ; Retina/chemistry ; Substrate Specificity ; Transferases/*deficiency/genetics ; rab1 GTP-Binding Proteins ; rab3 GTP-Binding Proteins
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  • 72
    Publication Date: 1993-12-24
    Description: X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The gene for the gap junction protein connexin32 is located in the same chromosomal segment, which led to its consideration as a candidate gene for CMTX. With the use of Northern (RNA) blot and immunohistochemistry technique, it was found that connexin32 is normally expressed in myelinated peripheral nerve. Direct sequencing of the connexin32 gene showed seven different mutations in affected persons from eight CMTX families. These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32 plays an important role in peripheral nerve.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bergoffen, J -- Scherer, S S -- Wang, S -- Scott, M O -- Bone, L J -- Paul, D L -- Chen, K -- Lensch, M W -- Chance, P F -- Fischbeck, K H -- GM37751/GM/NIGMS NIH HHS/ -- NS01565/NS/NINDS NIH HHS/ -- NS08075/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Dec 24;262(5142):2039-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of Pennsylvania Medical School, Children's Hospital of Philadelphia 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8266101" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Charcot-Marie-Tooth Disease/*genetics ; Chromosome Mapping ; Connexins/analysis/*genetics ; Female ; Genetic Linkage ; Humans ; Male ; Molecular Sequence Data ; *Mutation ; Nerve Fibers, Myelinated/chemistry ; Nerve Tissue Proteins/analysis ; Peripheral Nerves/chemistry ; Rats ; X Chromosome
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  • 73
    Publication Date: 1993-04-02
    Description: In pituitary gonadotropes, gonadotropin-releasing hormone (GnRH) induces the rhythmic release of Ca2+ from an inositol 1,4,5-trisphosphate (IP3)-sensitive store. Simultaneous measurement of the concentration of cytosolic free Ca2+ ([Ca2+]i) and exocytosis in single identified gonadotropes showed that each elevation of [Ca2+]i induced a burst of exocytosis. These phenomena were largely suppressed by buffering of [Ca2+]i but persisted in the absence of extracellular Ca2+. Activation of voltage-gated Ca2+ channels by brief depolarizations seldom supplied enough Ca2+ for exocytosis, but [Ca2+]i elevations induced by photolysis of caged IP3 did trigger exocytosis, confirming that GnRH-stimulated gonadotropic hormone secretion is closely coupled to intracellular Ca2+ release. Agonist-induced oscillations of [Ca2+]i in secretory cells may be a mechanism to optimize the secretory output while avoiding the toxic effects of sustained elevation of [Ca2+]i.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tse, A -- Tse, F W -- Almers, W -- Hille, B -- New York, N.Y. -- Science. 1993 Apr 2;260(5104):82-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8385366" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Calcium/*metabolism ; Calcium Channels/drug effects/physiology ; Cytoplasmic Granules/drug effects/physiology ; Electrophysiology ; Exocytosis/*drug effects ; Gonadotropin-Releasing Hormone/administration & dosage/*pharmacology ; Inositol 1,4,5-Trisphosphate/pharmacology ; Male ; Periodicity ; Photolysis ; Pituitary Gland/drug effects/*physiology/ultrastructure ; Rats ; Rats, Sprague-Dawley
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  • 74
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-10-01
    Description: When the recognition sequence of a ribozyme is extended beyond a certain length, turnover is slowed and specificity is decreased. Here, it is shown that a protein can help a ribozyme overcome these general limitations on ribozyme activity. Cleavage of an RNA oligonucleotide by a hammerhead ribozyme is enhanced 10- to 20-fold upon addition of a protein derived from the p7 nucleocapsid (NC) protein of human immunodeficiency virus-type 1. The NC protein also enhances the ability of the ribozyme to discriminate between cleavage of RNA oligonucleotides with differing sequences. These catalytic improvements can be attributed to the strand exchange activity of this RNA binding protein. It is conceivable that endogenous or added proteins may provide analogous increases in ribozyme activity and specificity in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tsuchihashi, Z -- Khosla, M -- Herschlag, D -- New York, N.Y. -- Science. 1993 Oct 1;262(5130):99-102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7692597" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *Capsid Proteins ; Catalysis ; DNA, Single-Stranded/metabolism ; Gene Products, gag/*metabolism ; Kinetics ; Molecular Sequence Data ; Oligoribonucleotides/*metabolism ; RNA/*metabolism ; RNA, Catalytic/chemistry/*metabolism ; Substrate Specificity ; *Viral Proteins ; Zinc Fingers ; gag Gene Products, Human Immunodeficiency Virus
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  • 75
    Publication Date: 1993-02-05
    Description: Myotonic dystrophy (DM) is an autosomal-dominant disorder that affects 1 in 8000 individuals. Amplification of an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene, correlates with a more severe DM phenotype. In three cases, the number of CTG repeats was reduced during the transmission of the DM allele; in one of these cases, the number was reduced to within the normal range and correlated at least with a delay in the onset of clinical signs of DM. Haplotype data of six polymorphic markers in the DM gene region indicate that, in this latter case, two stretches of the affected chromosome had been exchanged with that region of the wild-type chromosome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Hoy, K L -- Tsilfidis, C -- Mahadevan, M S -- Neville, C E -- Barcelo, J -- Hunter, A G -- Korneluk, R G -- New York, N.Y. -- Science. 1993 Feb 5;259(5096):809-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of Ottawa, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8094260" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Age Factors ; Alleles ; Apolipoprotein C-II ; Apolipoproteins C/genetics ; Base Sequence ; *Chromosomes, Human, Pair 19 ; DNA/genetics/isolation & purification ; Female ; Genes, Dominant ; Haplotypes ; Humans ; Male ; Molecular Sequence Data ; *Mutation ; Myotonic Dystrophy/*genetics/physiopathology ; Oligodeoxyribonucleotides ; Pedigree ; Polymerase Chain Reaction ; *Polymorphism, Restriction Fragment Length ; *Repetitive Sequences, Nucleic Acid
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  • 76
    Publication Date: 1993-02-12
    Description: The ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and immunoglobulin secretion. Abnormalities in the CD40L gene were associated with an X-linked immunodeficiency in humans [hyper-IgM (immunoglobulin M) syndrome]. This disease is characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. CD40L complementary DNAs from three of four patients with this syndrome contained distinct point mutations. Recombinant expression of two of the mutant CD40L complementary DNAs resulted in proteins incapable of binding to CD40 and unable to induce proliferation or IgE secretion from normal B cells. Activated T cells from the four affected patients failed to express wild-type CD40L, although their B cells responded normally to wild-type CD40L. Thus, these CD40L defects lead to a T cell abnormality that results in the failure of patient B cells to undergo immunoglobulin class switching.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, R C -- Armitage, R J -- Conley, M E -- Rosenblatt, H -- Jenkins, N A -- Copeland, N G -- Bedell, M A -- Edelhoff, S -- Disteche, C M -- Simoneaux, D K -- A125129/PHS HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):990-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7679801" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/*metabolism ; Antigens, CD40 ; Antigens, Differentiation, B-Lymphocyte/*metabolism ; Base Sequence ; CD40 Ligand ; DNA/chemistry/genetics ; Humans ; Immunoglobulin M/*blood ; Immunologic Deficiency Syndromes/*genetics/immunology ; Ligands ; Male ; Membrane Glycoproteins/*genetics ; Mice ; Molecular Sequence Data ; *Point Mutation ; Polymerase Chain Reaction ; T-Lymphocytes/*immunology ; Transfection ; *X Chromosome
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-09-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diamond, R -- New York, N.Y. -- Science. 1993 Sep 3;261(5126):1258-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8362240" target="_blank"〉PubMed〈/a〉
    Keywords: Civil Rights ; Ethics, Medical ; *Genes ; Genetic Testing ; *Homosexuality ; Humans ; Male
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  • 78
    Publication Date: 1993-01-29
    Description: Nonsense mutations create a premature signal for the termination of translation of messenger RNA. Such mutations have been observed to cause a severe reduction in the amount of mutant allele transcript or to generate a peptide truncated at the carboxyl end. Analysis of fibrillin transcript from a patient with Marfan syndrome revealed the skipping of a constitutive exon containing a nonsense mutation. Similar results were observed for two nonsense mutations in the gene encoding ornithine delta-aminotransferase from patients with gyrate atrophy. All genomic DNA sequences flanking these exons that are known to influence RNA splicing were unaltered, which suggests that nonsense mutations can alter splice site selection in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dietz, H C -- Valle, D -- Francomano, C A -- Kendzior, R J Jr -- Pyeritz, R E -- Cutting, G R -- AR-41135/AR/NIAMS NIH HHS/ -- HG-00373/HG/NHGRI NIH HHS/ -- RR-00722/RR/NCRR NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1993 Jan 29;259(5095):680-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430317" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cells, Cultured ; DNA/*genetics/isolation & purification ; *Exons ; Female ; Fibroblasts/physiology ; Humans ; Male ; Marfan Syndrome/*genetics ; Microfilament Proteins/*genetics ; Molecular Sequence Data ; *Mutation ; Oligodeoxyribonucleotides ; Polymerase Chain Reaction/methods ; Reference Values
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 1993 May 14;260(5110):897.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493522" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*transmission ; *Dentists ; Female ; Florida ; Humans ; Male ; *Patients
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  • 80
    Publication Date: 1993-02-05
    Description: Recoverin, a calcium ion (Ca2+)-binding protein of vertebrate photoreceptors, binds to photoreceptor membranes when the Ca2+ concentration is greater than 1 micromolar. This interaction requires a fatty acyl residue covalently linked to the recoverin amino (NH2)-terminus. Removal of the acyl residue, either by proteolytic cleavage of the NH2-terminus or by production of nonacylated recoverin, prevented recoverin from binding to membranes. The acylated recoverin NH2-terminus could be cleaved by trypsin only when Ca2+ was bound to recoverin. These results suggest that the hydrophobic NH2-terminus is constrained in Ca(2+)-free recoverin and liberated by Ca2+ binding. The hydrophobic acyl moiety of recoverin may interact with the membrane only when recoverin binds Ca2+.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dizhoor, A M -- Chen, C K -- Olshevskaya, E -- Sinelnikova, V V -- Phillipov, P -- Hurley, J B -- EYO6641/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 5;259(5096):829-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle 98195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8430337" target="_blank"〉PubMed〈/a〉
    Keywords: 1,2-Dipalmitoylphosphatidylcholine ; Acylation ; Animals ; Antigens, Neoplasm/isolation & purification/*metabolism ; Calcium/*metabolism/pharmacology ; Calcium-Binding Proteins/isolation & purification/*metabolism ; Cattle ; Cell Membrane/metabolism ; Egtazic Acid/pharmacology ; Electrophoresis, Polyacrylamide Gel ; *Eye Proteins ; Hippocalcin ; Kinetics ; *Lipoproteins ; Liposomes ; Membrane Proteins/isolation & purification/*metabolism ; Molecular Weight ; Myristic Acid ; Myristic Acids/*metabolism ; *Nerve Tissue Proteins ; Peptide Fragments/isolation & purification ; Phosphatidylserines ; Protein Binding ; Recoverin ; Rod Cell Outer Segment/*metabolism
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  • 81
    Publication Date: 1993-10-15
    Description: Repetitive activation of excitatory synapses in the hippocampus produces a persistent enhancement of synaptic efficiency known as long-term potentiation (LTP). In anesthetized and in freely moving rats, the induction of LTP in the perforant path led to a transient increase in the amount of messenger RNA (mRNA) coding for a presynaptic glutamate receptor (GR33) in dentate granule cells. The amount of GR33 mRNA was increased for at least 5 hours after the induction of LTP but was indistinguishable from control values 1 day after induction. The N-methyl-D-aspartate receptor antagonist 2-aminophosphonovalerate prevented the induction of both LTP and the increase in GR33 mRNA. The amount of GR33 protein was increased in the mossy fiber terminal zone of dentate granule cells 5 hours after the induction of LTP. These results suggest that the induction of LTP in synapses at one stage in a neural network may lead to modification in synaptic function at the next stage in the network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Smirnova, T -- Laroche, S -- Errington, M L -- Hicks, A A -- Bliss, T V -- Mallet, J -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):433-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de genetique moleculaire de la neurotransmission et des processus neurodegeneratifs, Centre National de la Recherche Scientifique (CNRS), Gif-sur-Yvette, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8105538" target="_blank"〉PubMed〈/a〉
    Keywords: 2-Amino-5-phosphonovalerate/pharmacology ; Animals ; Electric Stimulation ; Evoked Potentials ; Gene Expression ; Hippocampus/*metabolism/physiology ; In Situ Hybridization ; Male ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate/biosynthesis/*genetics ; Receptors, Presynaptic/biosynthesis/*genetics ; Synapses/*metabolism
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  • 82
    Publication Date: 1993-10-22
    Description: Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunner, H G -- Nelen, M -- Breakefield, X O -- Ropers, H H -- van Oost, B A -- NS 21921/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 22;262(5133):578-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, University Hospital Nijmegen, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211186" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Cell Line ; Cells, Cultured ; Female ; *Genes ; Humans ; Intellectual Disability/enzymology/*genetics ; Male ; Monoamine Oxidase/deficiency/*genetics ; Pedigree ; Phenotype ; *Point Mutation ; Skin/enzymology ; Syndrome ; X Chromosome
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  • 83
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-09-03
    Description: Cyclic adenosine diphosphoribose (cADPR), a recently discovered metabolite of nicotinamide adenine dinucleotide (NAD), is a potent calcium-releasing agent postulated to be a new second messenger. An enzyme that catalyzes the synthesis of cADPR from NAD and the hydrolysis of cADPR to ADP-ribose (ADPR) was purified to homogeneity from canine spleen microsomes. The net conversion of NAD to ADPR categorizes this enzyme as an NAD glycohydrolase. NAD glycohydrolases are ubiquitous membrane-bound enzymes that have been known for many years but whose function has not been identified. The results presented here suggest that these enzymes may function in the regulation of calcium homeostasis by the ability to synthesize and degrade cADPR.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, H -- Jacobson, E L -- Jacobson, M K -- CA43894/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 3;261(5126):1330-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of North Texas Health Science Center at Fort Worth 76107.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8395705" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate Ribose/*analogs & derivatives/biosynthesis/metabolism ; Animals ; Calcium/metabolism ; Cyclic ADP-Ribose ; Dogs ; Hydrolysis ; Kinetics ; NAD/metabolism ; NAD+ Nucleosidase/isolation & purification/*metabolism ; Spleen/enzymology
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  • 84
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-04-30
    Description: Long-finned pilot whales swim in large, extremely cohesive social groups known as pods. Molecular typing revealed that pod members form a single extended family. Mature males neither disperse from nor mate within their natal pods, a situation unusual for mammals. Such behavior could be explained in terms of inclusive fitness benefits gained by adult males helping the large number of female relatives with which they swim.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amos, B -- Schlotterer, C -- Tautz, D -- New York, N.Y. -- Science. 1993 Apr 30;260(5108):670-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cambridge University, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8480176" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; DNA, Satellite/*genetics ; Female ; Genotype ; Male ; Molecular Sequence Data ; Oligodeoxyribonucleotides/genetics ; Repetitive Sequences, Nucleic Acid ; Sexual Behavior, Animal ; *Social Behavior ; Whales/genetics/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 85
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-06-18
    Description: The reinforcing properties of cocaine are probably mediated by the mesocorticolimbic dopamine pathways in the central nervous system, but not all of the dopamine receptor subtypes involved in cocaine's reinforcing actions have been clearly identified. Recently, the D-3 receptor has been cloned, and its distribution in the brain has been found to be relatively restricted to limbic projections of the midbrain dopamine system. The D-3-selective compounds 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT) and quinpirole potently decreased cocaine self-administration in the rat at doses that were not by themselves reinforcing. Moreover, three dopamine receptor agonists had affinities for binding to the D-3 receptor that correlated highly with their relative potencies in decreasing cocaine self-administration. The D-3 receptor may be involved in the reinforcing effects of cocaine and may be a useful target for the development of new pharmacotherapies for cocaine abuse.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caine, S B -- Koob, G F -- NIDA DA04398/DA/NIDA NIH HHS/ -- NIDA DA05478/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1993 Jun 18;260(5115):1814-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8099761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apomorphine/pharmacology ; Cocaine/*administration & dosage ; Dopamine Agents/*pharmacology ; Dose-Response Relationship, Drug ; Ergolines/pharmacology ; Male ; Quinpirole ; Rats ; Rats, Wistar ; Receptors, Dopamine/*metabolism ; *Receptors, Dopamine D2 ; Receptors, Dopamine D3 ; Reinforcement (Psychology) ; Self Administration ; Tetrahydronaphthalenes/pharmacology
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  • 86
    Publication Date: 1993-07-30
    Description: A hemispheric asymmetry in the functional activation of the human motor cortex during contralateral (C) and ipsilateral (I) finger movements, especially in right-handed subjects, was documented with nuclear magnetic resonance imaging at high field strength (4 tesla). Whereas the right motor cortex was activated mostly during contralateral finger movements in both right-handed (C/I mean area of activation = 36.8) and left-handed (C/I = 29.9) subjects, the left motor cortex was activated substantially during ipsilateral movements in left-handed subjects (C/I = 5.4) and even more so in right-handed subjects (C/I = 1.3).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, S G -- Ashe, J -- Hendrich, K -- Ellermann, J M -- Merkle, H -- Ugurbil, K -- Georgopoulos, A P -- HL32427/HL/NHLBI NIH HHS/ -- HL33600/HL/NHLBI NIH HHS/ -- RR08079/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 Jul 30;261(5121):615-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Magnetic Resonance Research (CMRR), University of Minnesota Medical School, Minneapolis 55455.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8342027" target="_blank"〉PubMed〈/a〉
    Keywords: *Brain Mapping ; Female ; *Functional Laterality ; Humans ; *Magnetic Resonance Imaging ; Male ; Motor Cortex/anatomy & histology/*physiology
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  • 87
    Publication Date: 1993-07-16
    Description: The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0 (P = 10(-5), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hamer, D H -- Hu, S -- Magnuson, V L -- Hu, N -- Pattatucci, A M -- New York, N.Y. -- Science. 1993 Jul 16;261(5119):321-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8332896" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; *Genes ; *Genetic Linkage ; Genetic Markers ; Genotype ; *Homosexuality ; Humans ; Male ; Pedigree ; Phenotype ; *X Chromosome
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  • 88
    Publication Date: 1993-01-22
    Description: The function of neuropeptide Y, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists. An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the rat Y1 receptor was constructed and added to cultures of rat cortical neurons. This treatment resulted in a reduced density of Y1 (but not Y2) receptors and diminished the decrease in adenosine 3',5'-monophosphate (cAMP) usually seen after Y1 receptor activation. Repeated injection of the same oligodeoxynucleotide into the lateral cerebral ventricle of rats was followed by a similar reduction of cortical Y1 (but not Y2) receptors. Such antisense-treated animals displayed behavioral signs of anxiety. Thus, specific inhibition of neurotransmitter receptor expression can be accomplished in the living brain and demonstrates that altered central neuropeptide Y transmission produces an anxiety-like state.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wahlestedt, C -- Pich, E M -- Koob, G F -- Yee, F -- Heilig, M -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8380941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Anxiety ; Base Sequence ; Cells, Cultured ; Cerebral Cortex/*physiology ; Cyclic AMP/metabolism ; Down-Regulation ; Embryo, Mammalian ; Learning ; Male ; Molecular Sequence Data ; Neurons/drug effects/*physiology ; Neuropeptide Y/*physiology ; Oligodeoxyribonucleotides ; Oligonucleotides, Antisense/*pharmacology ; Polymerase Chain Reaction ; Rats ; Rats, Wistar ; Receptors, Neuropeptide Y/*drug effects/*genetics/metabolism
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  • 89
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J -- New York, N.Y. -- Science. 1993 May 7;260(5109):751-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8484115" target="_blank"〉PubMed〈/a〉
    Keywords: *Chromosomes, Human, Pair 2 ; Colonic Neoplasms/*genetics ; Colorectal Neoplasms/*genetics ; DNA, Satellite/*genetics ; Disease Susceptibility ; Female ; *Genes ; Genetic Markers ; Humans ; Male ; Mutation
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  • 90
    Publication Date: 1993-01-22
    Description: The mechanism of interleukin-1 (IL-1) signaling is unknown. Tumor necrosis factor-alpha uses a signal transduction pathway that involves sphingomyelin hydrolysis to ceramide and stimulation of a ceramide-activated protein kinase. In intact EL4 thymoma cells, IL-1 beta similarly stimulated a rapid decrease of sphingomyelin and an elevation of ceramide, and enhanced ceramide-activated protein kinase activity. This cascade was also activated by IL-1 beta in a cell-free system, demonstrating tight coupling to the receptor. Exogenous sphingomyelinase, but not phospholipases A2, C, or D, in combination with phorbol ester replaced IL-1 beta to stimulate IL-2 secretion. Thus, IL-1 beta signals through the sphingomyelin pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathias, S -- Younes, A -- Kan, C C -- Orlow, I -- Joseph, C -- Kolesnick, R N -- R0-1-CA-42385/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):519-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Signal Transduction, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8424175" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell-Free System ; Ceramides/*metabolism ; Dose-Response Relationship, Drug ; Interleukin-1/*pharmacology ; Interleukin-2/biosynthesis ; Kinetics ; Mice ; Molecular Sequence Data ; Protein Kinases/metabolism ; Signal Transduction/*drug effects ; Sphingomyelin Phosphodiesterase/pharmacology ; Sphingomyelins/*metabolism ; Substrate Specificity ; Thymoma ; Thymus Neoplasms ; Tumor Cells, Cultured ; Type C Phospholipases/pharmacology
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  • 91
    Publication Date: 1993-06-11
    Description: It is widely believed that gene flow connected many shallow water populations of the Caribbean and eastern Pacific until the Panama seaway closed 3.0 to 3.5 million years ago. Measurements of biochemical and reproductive divergence for seven closely related, transisthmian pairs of snapping shrimps (Alpheus) indicate, however, that isolation was staggered rather than simultaneous. The four least divergent pairs provide the best estimate for rates of molecular divergence and speciation. Ecological, genetic, and geological data suggest that gene flow was disrupted for the remaining three pairs by environmental change several million years before the land barrier was complete.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knowlton, N -- Weigt, L A -- Solorzano, L A -- Mills, D K -- Bermingham, E -- New York, N.Y. -- Science. 1993 Jun 11;260(5114):1629-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Smithsonian Tropical Research Institute, Balboa, Republic of Panama.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8503007" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Base Sequence ; DNA, Mitochondrial/*genetics ; Decapoda (Crustacea)/enzymology/*genetics ; Female ; Genotype ; Geological Phenomena ; Geology ; Isoenzymes/*genetics ; Male ; Molecular Sequence Data ; Panama ; *Phylogeny
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  • 92
    Publication Date: 1993-02-19
    Description: Ligand-gated ion channels gated by glutamate constitute the major excitatory neurotransmitter system in the mammalian brain. The functional modulation of GluR6, a kainate-activated glutamate receptor, by adenosine 3',5'-monophosphate-dependent protein kinase A (PKA) was examined with receptors expressed in human embryonic kidney cells. Kainate-evoked currents underwent a rapid desensitization that was blocked by lectins. Kainate currents were potentiated by intracellular perfusion of PKA, and this potentiation was blocked by co-application of an inhibitory peptide. Site-directed mutagenesis was used to identify the site or sites of phosphorylation on GluR6. Although mutagenesis of two serine residues, Ser684 and Ser666, was required for complete abolition of the PKA-induced potentiation, Ser684 may be the preferred site of phosphorylation in native GluR6 receptor complexes. These results indicate that glutamate receptor function can be directly modulated by protein phosphorylation and suggest that a dynamic regulation of excitatory receptors could be associated with some forms of learning and memory in the mammalian brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, L Y -- Taverna, F A -- Huang, X P -- MacDonald, J F -- Hampson, D R -- New York, N.Y. -- Science. 1993 Feb 19;259(5098):1173-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8382377" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Binding Sites ; Brain/*physiology ; Cells, Cultured ; Concanavalin A/pharmacology ; Evoked Potentials/drug effects ; Humans ; Kainic Acid/*pharmacology ; Kidney ; Kinetics ; Membrane Potentials/drug effects ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligodeoxyribonucleotides ; Protein Kinases/*metabolism ; Receptors, Glutamate/drug effects/genetics/*physiology ; Receptors, Kainic Acid ; Serine ; Wheat Germ Agglutinins/pharmacology
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  • 93
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-21
    Description: A method is described here for identifying good protease substrates among approximately 10(7) possible sequences. A library of fusion proteins was constructed containing an amino-terminal domain used to bind to an affinity support, followed by a randomized protease substrate sequence and the carboxyl-terminal domain of M13 gene III. Each fusion protein was displayed as a single copy on filamentous phagemid particles (substrate phage). Phage were then bound to an affinity support and treated with the protease of interest. Phage with good protease substrates were released, whereas phage with substrates that resisted proteolysis remained bound. After several rounds of binding, proteolysis, and phagemid propagation, sensitive and resistant substrate sequences were identified for two different proteases, a variant of subtilisin and factor Xa. The technique may also be useful for studying the sequence specificity of a variety of posttranslational modifications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matthews, D J -- Wells, J A -- New York, N.Y. -- Science. 1993 May 21;260(5111):1113-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Protein Engineering, Genentech, South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493554" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacteriophages/*genetics ; Base Sequence ; Computer Simulation ; Factor Xa/chemistry/*metabolism ; Genetic Vectors ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oligopeptides/chemistry/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Substrate Specificity ; Subtilisins/chemistry/genetics/*metabolism
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  • 94
    Publication Date: 1993-07-23
    Description: Concentrations of plasma high density lipoprotein (HDL) are inversely correlated with atherosclerotic coronary artery disease. The two most abundant protein constituents of HDL are apolipoproteins A-I and A-II (apoA-I and apoA-II). ApoA-I is required for assembly of HDL and, when overexpressed in transgenic mice, confers resistance to early atherosclerosis. The present studies reveal that transgenic mice that overexpress mouse apoA-II had elevated HDL-cholesterol concentrations but, nevertheless, exhibited increased atherosclerotic lesion development as compared to normal mice. The HDL in the transgenic mice was larger and had an increased ratio of apoA-II to apoA-I. Thus, both the composition and amount of HDL appear to be important determinants of atherosclerosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warden, C H -- Hedrick, C C -- Qiao, J H -- Castellani, L W -- Lusis, A J -- HL-07386/HL/NHLBI NIH HHS/ -- HL-28481/HL/NHLBI NIH HHS/ -- HL-42488/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1993 Jul 23;261(5120):469-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of California, Los Angeles 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8332912" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apolipoprotein A-I/physiology ; Apolipoprotein A-II/genetics/*physiology ; Arteriosclerosis/*blood/genetics ; Cholesterol/blood ; Crosses, Genetic ; Female ; Lipoproteins, HDL/blood/chemistry ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic
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  • 95
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watson, T -- New York, N.Y. -- Science. 1993 May 14;260(5110):888-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8493518" target="_blank"〉PubMed〈/a〉
    Keywords: Career Mobility ; Female ; Humans ; Male ; *National Institutes of Health (U.S.)/organization & administration ; Salaries and Fringe Benefits ; United States ; *Women, Working
    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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  • 96
    Publication Date: 1993-02-12
    Description: To investigate the mechanism of interaction of the toxin colicin E1 with membranes, three cysteine substitution mutants and the wild type of the channel-forming fragment were spin labeled at the unique thiol. Time-resolved interaction of these labeled proteins with phospholipid vesicles was investigated with stopped-flow electron paramagnetic resonance spectroscopy. The fragment interacts with neutral bilayers at low pH, indicating that the interaction is hydrophobic rather than electrostatic. The interaction occurs in at least two distinct steps: (i) rapid adsorption to the surface; and (ii) slow, rate-limiting insertion of the hydrophobic central helices into the membrane interior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shin, Y K -- Levinthal, C -- Levinthal, F -- Hubbell, W L -- EY05216/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):960-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jules Stein Eye Institute, University of California, Los Angeles 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8382373" target="_blank"〉PubMed〈/a〉
    Keywords: Adsorption ; Binding Sites ; Cell Membrane/*metabolism ; Colicins/chemistry/genetics/*metabolism ; Cysteine/genetics ; Electron Spin Resonance Spectroscopy ; Hydrogen-Ion Concentration ; Kinetics ; Lipid Bilayers/metabolism ; *Mutagenesis ; Peptide Fragments/metabolism ; Protein Structure, Secondary ; *Spin Labels
    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
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-02-12
    Description: G protein-mediated inhibition of voltage-activated calcium channels by neurotransmitters has important consequences for the control of synaptic strength. Single-channel recordings of N-type calcium channels in frog sympathetic neurons reveal at least three distinct patterns of gating, designated low-Po, medium-Po, and high-Po modes according to their probability of being open (Po) at -10 millivolts. The high-Po mode is responsible for the bulk of divalent cation entry in the absence of neurotransmitter. Norepinephrine greatly decreased the prevalence of high-Po gating and increased the proportion of time a channel exhibited low-Po behavior or no activity at all, which thereby reduced the overall current. Directly observed patterns of transition between the various modes suggest that activated G protein alters the balance between modal behaviors that freely interconvert even in the absence of modulatory signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delcour, A H -- Tsien, R W -- HL13156/HL/NHLBI NIH HHS/ -- NS24607/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 12;259(5097):980-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Beckman Center, Stanford University Medical Center, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8094902" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anura ; Calcium Channels/*drug effects/*physiology ; Cations, Divalent ; Electric Stimulation ; Electrophysiology ; GTP-Binding Proteins/physiology ; Ion Channel Gating/*physiology ; Kinetics ; Neurons/physiology ; Neurotransmitter Agents/*pharmacology ; Norepinephrine/pharmacology ; Sympathetic Nervous System/cytology/physiology ; Synapses/physiology
    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
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1993-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aldhous, P -- New York, N.Y. -- Science. 1993 Mar 5;259(5100):1403-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8383877" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Male ; Ovum/physiology ; Receptors, Cell Surface/genetics/*physiology ; Sea Urchins ; *Sperm-Ovum Interactions ; Spermatozoa/physiology
    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: 1993-03-12
    Description: Betacellulin, a member of the epidermal growth factor family, has been identified in the conditioned medium of cell lines derived from mouse pancreatic beta cell tumors. Betacellulin is a 32-kilodalton glycoprotein that appears to be processed from a larger transmembrane precursor by proteolytic cleavage. The carboxyl-terminal domain of betacellulin has 50 percent sequence similarity with that of rat transforming growth factor alpha. Betacellulin is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shing, Y -- Christofori, G -- Hanahan, D -- Ono, Y -- Sasada, R -- Igarashi, K -- Folkman, J -- CA 70118/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Mar 12;259(5101):1604-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, Children's Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8456283" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Amino Acid Sequence ; Animals ; Base Sequence ; Betacellulin ; Cell Division/drug effects ; Cells, Cultured ; DNA Replication/drug effects ; Endothelium, Vascular/cytology/drug effects ; Epidermal Growth Factor/pharmacology ; Growth Substances/*genetics/isolation & purification/pharmacology ; Humans ; *Intercellular Signaling Peptides and Proteins ; Islets of Langerhans/physiopathology ; Kinetics ; Mice ; Molecular Sequence Data ; Muscle, Smooth, Vascular/cytology/drug effects ; Oligodeoxyribonucleotides ; Pancreatic Neoplasms/*physiopathology ; Pigment Epithelium of Eye/cytology/drug effects ; Polymerase Chain Reaction/methods ; Protein Precursors/genetics ; Rats ; Receptor, Epidermal Growth Factor/metabolism ; Recombinant Proteins/pharmacology ; Sequence Homology, Amino Acid ; Thymidine/metabolism ; Transforming Growth Factor alpha/genetics
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 1993-10-15
    Description: The capsular polysaccharide complex from Bacteroides fragilis promotes the formation of intra-abdominal abscesses--a pathologic host response to infecting microorganisms. This complex consists of two distinct polysaccharides, each with repeating units that have positively charged amino groups and negatively charged carboxyl or phosphate groups. Analysis of these polysaccharides as well as other charged carbohydrates before and after chemical modification revealed that these oppositely charged groups are required for the induction of intra-abdominal abscesses in a rat model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tzianabos, A O -- Onderdonk, A B -- Rosner, B -- Cisneros, R L -- Kasper, D L -- 1F32 AI 084901 AI/AI/NIAID NIH HHS/ -- 2T32AI07061-11AI/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1993 Oct 15;262(5132):416-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Channing Laboratory, Brigham and Women's Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8211161" target="_blank"〉PubMed〈/a〉
    Keywords: *Abdomen ; Abscess/*microbiology ; Animals ; Bacterial Capsules/*chemistry/toxicity ; Bacteroides Infections/*microbiology ; Bacteroides fragilis/*pathogenicity ; Carbohydrate Sequence ; Male ; Molecular Sequence Data ; Neisseria meningitidis/pathogenicity ; Polysaccharides, Bacterial/chemistry/toxicity ; Rats ; Rats, Wistar ; Salmonella typhi/pathogenicity ; Streptococcus pneumoniae/pathogenicity ; Structure-Activity Relationship
    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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