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  • Life Sciences (General)  (101)
  • Mice  (41)
  • Chemical Engineering  (36)
  • PHYSICS, ATOMIC, MOLECULAR, AND NUCLEAR
  • 1995-1999  (178)
  • 1965-1969
  • 1960-1964
  • 1996  (178)
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  • 1995-1999  (178)
  • 1965-1969
  • 1960-1964
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  • 1
    Publication Date: 1996-08-09
    Description: alpha2-Adrenergic receptors (alpha2ARs) present in the brainstem decrease blood pressure and are targets for clinically effective antihypertensive drugs. The existence of three alpha2AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha2AR agonists with imidazoline receptors has precluded an understanding of the role of individual alpha2AR subtypes in the hypotensive response. Gene targeting was used to introduce a point mutation into the alpha2aAR subtype in the mouse genome. The hypotensive response to alpha2AR agonists was lost in the mutant mice, demonstrating that the alpha2aAR subtype plays a principal role in this response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacMillan, L B -- Hein, L -- Smith, M S -- Piascik, M T -- Limbird, L E -- HL38120/HL/NHLBI NIH HHS/ -- HL43671/HL/NHLBI NIH HHS/ -- HL48638/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 9;273(5276):801-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8670421" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-2 Receptor Agonists ; Adrenergic alpha-Agonists/pharmacology ; Animals ; Antihypertensive Agents/pharmacology ; Base Sequence ; Blood Pressure/drug effects/*physiology ; Brain Stem/physiology ; Brimonidine Tartrate ; Gene Targeting ; Heart Rate/drug effects/physiology ; Imidazoles/pharmacology ; Medetomidine ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Point Mutation ; Quinoxalines/pharmacology ; Receptors, Adrenergic, alpha-2/genetics/metabolism/*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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  • 2
    Publication Date: 1996-11-08
    Description: Lipid A constitutes the outer monolayer of the outer membrane of Gram-negative bacteria and is essential for bacterial growth. Synthetic antibacterials were identified that inhibit the second enzyme (a unique deacetylase) of lipid A biosynthesis. The inhibitors are chiral hydroxamic acids bearing certain hydrophobic aromatic moieties. They may bind to a metal in the active site of the deacetylase. The most potent analog (with an inhibition constant of about 50 nM) displayed a minimal inhibitory concentration of about 1 microgram per milliliter against Escherichia coli, caused three logs of bacterial killing in 4 hours, and cured mice infected with a lethal intraperitoneal dose of E. coli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Onishi, H R -- Pelak, B A -- Gerckens, L S -- Silver, L L -- Kahan, F M -- Chen, M H -- Patchett, A A -- Galloway, S M -- Hyland, S A -- Anderson, M S -- Raetz, C R -- New York, N.Y. -- Science. 1996 Nov 8;274(5289):980-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Merck Research Laboratories, Rahway, NJ 07065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8875939" target="_blank"〉PubMed〈/a〉
    Keywords: Amidohydrolases/*antagonists & inhibitors/metabolism ; Animals ; Anti-Bacterial Agents/chemistry/*pharmacology ; Binding Sites ; Escherichia coli/drug effects ; Escherichia coli Infections/drug therapy ; Gram-Negative Bacteria/*drug effects ; Hydroxamic Acids/chemistry/*pharmacology ; Lipid A/*biosynthesis ; Mice ; Microbial Sensitivity Tests ; Oxazoles/chemistry/pharmacology ; Pseudomonas/drug effects ; Serratia/drug effects ; Stereoisomerism ; 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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  • 3
    Publication Date: 1996-07-26
    Description: Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14- amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wrighton, N C -- Farrell, F X -- Chang, R -- Kashyap, A K -- Barbone, F P -- Mulcahy, L S -- Johnson, D L -- Barrett, R W -- Jolliffe, L K -- Dower, W J -- New York, N.Y. -- Science. 1996 Jul 26;273(5274):458-64.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Affymax Research Institute, 4001 Miranda Avenue, Palo Alto, CA 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662529" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bacteriophages ; Cell Division/drug effects ; Cell Line ; Cloning, Molecular ; Erythropoiesis/drug effects ; Erythropoietin/chemistry/*metabolism/*pharmacology ; Humans ; Ligands ; Mice ; *Molecular Mimicry ; Molecular Sequence Data ; Mutagenesis ; Peptides, Cyclic/chemistry/*metabolism/*pharmacology ; Phosphorylation ; Protein Structure, Secondary ; Receptors, Erythropoietin/*agonists/chemistry/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Signal Transduction ; Solubility ; Tyrosine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2011-08-24
    Description: Recently developed molecular and genetic approaches have enabled the identification and functional characterization of novel genes encoding ion channels, ion carriers, and water channels of the plant plasma membrane.
    Keywords: Life Sciences (General)
    Type: Current opinion in cell biology (ISSN 0955-0674); Volume 8; 4; 458-67
    Format: text
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  • 5
    Publication Date: 2011-08-24
    Description: The authors consider three aspects of managing fatigue in the workplace. They provide a brief overview of important scientific findings related to sleep and circadian physiology that establish the psychobiological foundation of fatigue. Their major focus is on the relevance of these findings to operational settings. In addition, they provide examples to describe practical fatigue countermeasures that can be used in operational settings.
    Keywords: Life Sciences (General)
    Type: Behavioral medicine (Washington, D.C.) (ISSN 0896-4289); Volume 21; 4; 157-65
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  • 6
    Publication Date: 2011-08-24
    Description: The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.
    Keywords: Life Sciences (General)
    Type: Journal of leukocyte biology (ISSN 0741-5400); Volume 60; 1; 37-43
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  • 7
    Publication Date: 1996-01-19
    Description: About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4, a gene similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a transforming growth factor-beta (TGF-beta)-like signaling pathway. Potentially inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas that did not have homozygous deletions at 18q21.1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hahn, S A -- Schutte, M -- Hoque, A T -- Moskaluk, C A -- da Costa, L T -- Rozenblum, E -- Weinstein, C L -- Fischer, A -- Yeo, C J -- Hruban, R H -- Kern, S E -- CA62924/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Jan 19;271(5247):350-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8553070" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Sequence ; Animals ; Base Sequence ; Cell Division ; Chromosome Mapping ; *Chromosomes, Human, Pair 18 ; *DNA-Binding Proteins ; Gene Deletion ; Gene Expression ; *Genes, Tumor Suppressor ; Genetic Markers ; Humans ; Mice ; Molecular Sequence Data ; Mutation ; Neoplasm Transplantation ; Pancreatic Neoplasms/*genetics/pathology ; Proteins/chemistry/*genetics/physiology ; Signal Transduction ; Smad4 Protein ; *Trans-Activators ; Transforming Growth Factor beta/physiology ; Transplantation, Heterologous ; Tumor Cells, Cultured
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-11-01
    Description: CD22 is a surface glycoprotein of B lymphocytes that is rapidly phosphorylated on cytoplasmic tyrosines after antigen receptor cross-linking. Splenic B cells from mice with a disrupted CD22 gene were found to be hyperresponsive to receptor signaling: Heightened calcium fluxes and cell proliferation were obtained at lower ligand concentrations. The mice gave an augmented immune response, had an expanded peritoneal B-1 cell population, and contained increased serum titers of autoantibody. Thus, CD22 is a negative regulator of antigen receptor signaling whose onset of expression at the mature B cell stage may serve to raise the antigen concentration threshold required for B cell triggering.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Keefe, T L -- Williams, G T -- Davies, S L -- Neuberger, M S -- New York, N.Y. -- Science. 1996 Nov 1;274(5288):798-801.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8864124" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Antinuclear/blood ; Antibody Formation ; Antigens, CD/genetics/*immunology/metabolism ; Antigens, Differentiation, B-Lymphocyte/genetics/*immunology/metabolism ; B-Lymphocytes/*immunology/metabolism ; Calcium/metabolism ; *Cell Adhesion Molecules ; Female ; Gene Targeting ; Immunization ; Immunoglobulin M/blood ; Immunophenotyping ; *Lectins ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Phosphorylation ; Receptors, Antigen, B-Cell/immunology/physiology ; Sialic Acid Binding Ig-like Lectin 2 ; Signal Transduction ; Transfection
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    Electronic ISSN: 1095-9203
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  • 9
    Publication Date: 1996-10-11
    Description: The central event in the cellular immune response to invading microorganisms is the specific recognition of foreign peptides bound to major histocompatibility complex (MHC) molecules by the alphabeta T cell receptor (TCR). The x-ray structure of the complete extracellular fragment of a glycosylated alphabeta TCR was determined at 2.5 angstroms, and its orientation bound to a class I MHC-peptide (pMHC) complex was elucidated from crystals of the TCR-pMHC complex. The TCR resembles an antibody in the variable Valpha and Vbeta domains but deviates in the constant Calpha domain and in the interdomain pairing of Calpha with Cbeta. Four of seven possible asparagine-linked glycosylation sites have ordered carbohydrate moieties, one of which lies in the Calpha-Cbeta interface. The TCR combining site is relatively flat except for a deep hydrophobic cavity between the hypervariable CDR3s (complementarity-determining regions) of the alpha and beta chains. The 2C TCR covers the class I MHC H-2Kb binding groove so that the Valpha CDRs 1 and 2 are positioned over the amino-terminal region of the bound dEV8 peptide, the Vbeta chain CDRs 1 and 2 are over the carboxyl-terminal region of the peptide, and the Valpha and Vbeta CDR3s straddle the peptide between the helices around the central position of the peptide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia, K C -- Degano, M -- Stanfield, R L -- Brunmark, A -- Jackson, M R -- Peterson, P A -- Teyton, L -- Wilson, I A -- R01 CA58896/CA/NCI NIH HHS/ -- T32-A107244/PHS HHS/ -- New York, N.Y. -- Science. 1996 Oct 11;274(5285):209-19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and the Skaggs Institute of Chemical Biology, Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8824178" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbohydrate Sequence ; Cells, Cultured ; Crystallization ; Crystallography, X-Ray ; Drosophila melanogaster ; Glycosylation ; H-2 Antigens/*chemistry/immunology/metabolism ; Hydrogen Bonding ; Major Histocompatibility Complex ; Mice ; Models, Molecular ; Molecular Sequence Data ; Peptides/*chemistry/immunology/metabolism ; *Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptors, Antigen, T-Cell, alpha-beta/*chemistry/immunology/metabolism ; Recombinant Proteins ; T-Lymphocytes, Cytotoxic/*immunology
    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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  • 10
    Publication Date: 1996-02-16
    Description: Mice harboring mutations in the obese (ob) and diabetes (db) genes display similar phenotypes, and it has been proposed that these genes encode the ligand and receptor, respectively, for a physiologic pathway that regulates body weight. The cloning of ob, and the demonstration that it encodes a secreted protein (leptin) that binds specifically to a receptor (OB-R) in the brain, have validated critical aspects of this hypothesis. Here it is shown by genetic mapping and genomic analysis that mouse db, rat fatty (a homolog of db), and the gene encoding the OB-R are the same gene.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chua, S C Jr -- Chung, W K -- Wu-Peng, X S -- Zhang, Y -- Liu, S M -- Tartaglia, L -- Leibel, R L -- DK26687/DK/NIDDK NIH HHS/ -- DK47473/DK/NIDDK NIH HHS/ -- HD28047/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1996 Feb 16;271(5251):994-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Human Behavior and Metabolism, Rockefeller University, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8584938" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Blotting, Southern ; Carrier Proteins/*genetics ; Chromosome Mapping ; Cloning, Molecular ; DNA Mutational Analysis ; Diabetes Mellitus/*genetics ; Genetic Markers ; Leptin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Molecular Sequence Data ; Obesity/*genetics ; Phenotype ; Polymerase Chain Reaction ; Proteins/genetics ; Rats ; Rats, Inbred Strains ; *Receptors, Cell Surface ; Receptors, Cytokine/*genetics ; Receptors, Leptin
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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