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  • Articles  (334)
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  • Articles  (334)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-01-20
    Description: Human and murine mononuclear phagocytes express a high-affinity receptor for immunoglobulin G that plays a central role in macrophage antibody-dependent cellular cytotoxicity and clearance of immune complexes. The receptor (FcRI) may also be involved in CD4-independent infection of human macrophages by human immunodeficiency virus. This report describes the isolation of cDNA clones encoding the human FcRI by a ligand-mediated selection technique. Expression of the cDNAs in COS cells gave rise to immunoglobulin G binding of the expected affinity and subtype specificity. RNA blot analysis revealed expression of a 1.7-kilobase transcript in macrophages and in cells of the promonocytic cell line U937 induced with interferon-gamma. The extracellular region of FcRI consists of three immunoglobulin-like domains, two of which share homology with low-affinity receptor domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allen, J M -- Seed, B -- New York, N.Y. -- Science. 1989 Jan 20;243(4889):378-81.〈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/2911749" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blotting, Northern ; Cercopithecus aethiops ; Cloning, Molecular ; DNA/genetics ; Gene Expression Regulation ; Humans ; Molecular Sequence Data ; Molecular Weight ; Polymorphism, Genetic ; Receptors, Fc/*genetics ; Transfection
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-05-05
    Description: Tumor promoters may bring about events that lead to neoplastic transformation by inducing specific promotion-relevant effector genes. Functional activation of the transacting transcription factor AP-1 by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) may play an essential role in this process. Clonal genetic variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to promotion of transformation by TPA were transfected with 3XTRE-CAT, a construct that has AP-1 cis-enhancer sequences attached to a reporter gene encoding chloramphenicol acetyltransferase (CAT). Transfected JB6 P+, but not P- variants, showed TPA-inducible CAT synthesis. Epidermal growth factor, another transformation promoter in JB6 cells, also caused P+ specific induction of CAT gene expression. These results demonstrate an association between induced AP-1 function and sensitivity to promotion of neoplastic transformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bernstein, L R -- Colburn, N H -- New York, N.Y. -- Science. 1989 May 5;244(4904):566-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University, Department of Biology, Baltimore, MD 21218.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2541502" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Cell Transformation, Neoplastic ; Chloramphenicol O-Acetyltransferase/genetics ; Cloning, Molecular ; DNA-Binding Proteins/genetics/*physiology ; Epidermal Growth Factor/pharmacology ; Epidermis ; Gene Expression Regulation ; Genetic Variation ; Kinetics ; Mice ; Nucleic Acid Hybridization ; Plasmids ; Promoter Regions, Genetic ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-jun ; Simplexvirus/genetics ; Tetradecanoylphorbol Acetate/*pharmacology ; Transcription Factors/genetics/*physiology ; Transfection
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-01-20
    Description: Nerve growth factor (NGF) interacts with both high affinity (Kd = 10(-10)-10(-11)M) and low affinity (Kd = 10(-8)-10(-9)M) receptors; the binding of NGF to the high affinity receptor is correlated with biological actions of NGF. To determine whether a single NGF binding protein is common to both forms of the receptor, a full-length receptor cDNA was introduced in the NR18 cell line, an NGF receptor-deficient variant of the PC12 pheochromocytoma cell line. The transformant displayed (i) both high and low affinity receptors detectable by receptor binding; (ii) an affinity cross-linking pattern with 125I-labeled NGF similar to that of the parent PC12 cell line; and (iii) biological responsiveness to NGF as assayed by induction of c-fos transcription. These findings support the hypothesis that a single binding protein is common to both forms of the NGF receptor and suggest that an additional protein is required to produce the high affinity form of the NGF receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hempstead, B L -- Schleifer, L S -- Chao, M V -- HD23315/HD/NICHD NIH HHS/ -- NS-21072/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jan 20;243(4889):373-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology, 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/2536190" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blotting, Northern ; Cloning, Molecular ; Gene Expression Regulation ; Nerve Growth Factors/pharmacology ; Pheochromocytoma ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-fos ; Rats ; Receptors, Cell Surface/*genetics/metabolism ; Receptors, Nerve Growth Factor ; Transformation, Genetic ; Tumor Cells, Cultured
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  • 4
    Publication Date: 1989-04-28
    Description: Transcriptional activation of the human interleukin-2 (IL-2) gene, like induction of the IL-2 receptor alpha (IL-2R alpha) gene and the type 1 human immunodeficiency virus (HIV-1), is shown to be modulated by a kappa B-like enhancer element. Mutation of a kappa B core sequence identified in the IL-2 promoter (-206 to -195) partially inhibits both mitogen- and HTLV-I Tax-mediated activation of this transcription unit and blocks the specific binding of two inducible cellular factors. These kappa B-specific proteins (80 to 90 and 50 to 55 kilodaltons) similarly interact with the functional kappa B enhancer present in the IL-2R alpha promoter. These data suggest that these kappa B-specific proteins have a role in the coordinate regulation of this growth factor-growth factor receptor gene system that controls T cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoyos, B -- Ballard, D W -- Bohnlein, E -- Siekevitz, M -- Greene, W C -- A127053-01/PHS HHS/ -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):457-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mount Sinai Medical Center, Department of Microbiology, New York, NY 10029.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2497518" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line ; Cloning, Molecular ; DNA/metabolism ; DNA-Binding Proteins/*metabolism ; *Enhancer Elements, Genetic ; *Gene Expression Regulation ; Genes, Viral ; HIV-1/genetics ; HTLV-I Antigens/pharmacology ; Humans ; Immunoglobulin kappa-Chains/*genetics ; Interleukin-2/*genetics ; Molecular Weight ; Mutation ; Phytohemagglutinins/pharmacology ; Plasmids ; Promoter Regions, Genetic ; RNA, Messenger/biosynthesis ; T-Lymphocytes/metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Trans-Activators ; Transcription Factors/pharmacology ; Transcription, Genetic ; Transfection
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  • 5
    Publication Date: 1989-09-22
    Description: Soybean cultivars resistant to Pseudomonas syringae pathovar glycinea (Psg), the causal agent of bacterial blight, exhibit a hypersensitive (necrosis) reaction (HR) to infection. Psg strains carrying the avrB gene elicit the HR in soybean cultivars carrying the resistance gene Rpg1. Psg expressing avrB at a high level and capable of eliciting the HR in the absence of de novo bacterial RNA synthesis have been obtained in in vitro culture. Nutritional signals and regions within the Psg hrp gene cluster, an approximately 20-kilobase genomic region also necessary for pathogenicity, control avrB transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huynh, T V -- Dahlbeck, D -- Staskawicz, B J -- New York, N.Y. -- Science. 1989 Sep 22;245(4924):1374-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Pathology, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2781284" target="_blank"〉PubMed〈/a〉
    Keywords: Cloning, Molecular ; DNA Mutational Analysis ; Gene Expression Regulation ; Genes, Bacterial ; *Plant Diseases ; Promoter Regions, Genetic ; Pseudomonas/*genetics/growth & development/pathogenicity ; Regulatory Sequences, Nucleic Acid ; Restriction Mapping ; Soybeans/*genetics/microbiology ; Transcription, Genetic
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-05-19
    Description: Biochemical and electrophysiological studies suggest that odorants induce responses in olfactory sensory neurons via an adenylate cyclase cascade mediated by a G protein. An olfactory-specific guanosine triphosphate (GTP)-binding protein alpha subunit has now been characterized and evidence is presented suggesting that this G protein, termed Golf, mediates olfaction. Messenger RNA that encodes Golf alpha is expressed in olfactory neuroephithelium but not in six other tissues tested. Moreover, within the olfactory epithelium, Golf alpha appears to be expressed only by the sensory neurons. Specific antisera were used to localize Golf alpha protein to the sensory apparatus of the receptor neurons. Golf alpha shares extensive amino acid identity (88 percent) with the stimulatory G protein, Gs alpha. The expression of Golf alpha in S49 cyc- kin- cells, a line deficient in endogenous stimulatory G proteins, demonstrates its capacity to stimulate adenylate cyclase in a heterologous system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, D T -- Reed, R R -- New York, N.Y. -- Science. 1989 May 19;244(4906):790-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Biology and Genetic Johns Hopkins School of Medicine, Baltimore, MD 21205.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2499043" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; GTP-Binding Proteins/analysis/genetics/*physiology ; Gene Expression Regulation ; Immunoblotting ; Immunohistochemistry ; Molecular Sequence Data ; Neurons, Afferent/analysis/*physiology ; *Odors ; Olfactory Bulb/physiology ; Olfactory Mucosa/analysis/*innervation ; RNA, Messenger/analysis/genetics ; Rats ; Sequence Homology, Nucleic Acid ; *Signal Transduction ; Tissue Distribution ; Transfection
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  • 7
    Publication Date: 1989-01-27
    Description: During sporulation in Bacillus subtilis, expression of developmental genes spoIVCB and cotD is induced in the mother cell compartment of the sporangium at morphological stages IV and V, respectively. A 27-kilodalton RNA polymerase sigma factor called sigma K (or sigma 27) has been found that causes weak transcription of spoIVCB and strong transcription of cotD. A 14-kD protein was also discovered that changes the specificity of sigma K-containing RNA polymerase, greatly stimulating spoIVCB transcription and markedly repressing cotD transcription. Both sigma K and the 14-kD protein are products of genes known to be required for expression of specific genes in the mother cell. Thus, sigma K directs gene expression in the mother cell and it is proposed that inactivation or sequestering of the 14-kD protein switches the temporal pattern of gene expression during the transition from stages IV to V of development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kroos, L -- Kunkel, B -- Losick, R -- GM18568/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jan 27;243(4890):526-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2492118" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus subtilis/*genetics/physiology ; Cloning, Molecular ; DNA-Directed RNA Polymerases/*genetics/isolation & purification ; Electrophoresis, Polyacrylamide Gel ; Gene Expression Regulation ; Molecular Sequence Data ; Promoter Regions, Genetic ; Sigma Factor/*genetics/isolation & purification ; Spores, Bacterial/genetics ; Transcription Factors/*genetics ; Transcription, Genetic
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  • 8
    Publication Date: 1989-04-07
    Description: Protein engineering and x-ray crystallography have been used to study the role of a surface loop that is present in pancreatic phospholipases but is absent in snake venom phospholipases. Removal of residues 62 to 66 from porcine pancreatic phospholipase A2 does not change the binding constant for micelles significantly, but it improves catalytic activity up to 16 times on micellar (zwitterionic) lecithin substrates. In contrast, the decrease in activity on negatively charged substrates is greater than fourfold. A crystallographic study of the mutant enzyme shows that the region of the deletion has a well-defined structure that differs from the structure of the wild-type enzyme. No structural changes in the active site of the enzyme were detected.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuipers, O P -- Thunnissen, M M -- de Geus, P -- Dijkstra, B W -- Drenth, J -- Verheij, H M -- de Haas, G H -- New York, N.Y. -- Science. 1989 Apr 7;244(4900):82-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2704992" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Crystallography ; Enzyme Activation ; Kinetics ; Molecular Sequence Data ; Mutation ; Pancreas/enzymology ; Phospholipases/*metabolism ; Phospholipases A/genetics/*metabolism/physiology ; Phospholipases A2 ; *Protein Conformation ; Snake Venoms/analysis ; Structure-Activity Relationship ; Swine
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-07-14
    Description: DNA mismatch correction is a strand-specific process involving recognition of noncomplementary Watson-Crick nucleotide pairs and participation of widely separated DNA sites. The Escherichia coli methyl-directed reaction has been reconstituted in a purified system consisting of MutH, MutL, and MutS proteins, DNA helicase II, single-strand DNA binding protein, DNA polymerase III holoenzyme, exonuclease I, DNA ligase, along with ATP (adenosine triphosphate), and the four deoxynucleoside triphosphates. This set of proteins can process seven of the eight base-base mismatches in a strand-specific reaction that is directed by the state of methylation of a single d(GATC) sequence located 1 kilobase from the mispair.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lahue, R S -- Au, K G -- Modrich, P -- F32 GM12684/GM/NIGMS NIH HHS/ -- GM23719/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jul 14;245(4914):160-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2665076" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; *DNA Repair ; DNA, Bacterial/biosynthesis/*genetics ; Escherichia coli/*genetics ; Methylation ; Mutation
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  • 10
    Publication Date: 1989-08-18
    Description: CD4 is a cell surface glycoprotein that is thought to interact with nonpolymorphic determinants of class II major histocompatibility (MHC) molecules. CD4 is also the receptor for the human immunodeficiency virus (HIV), binding with high affinity to the HIV-1 envelope glycoprotein, gp120. Homolog-scanning mutagenesis was used to identify CD4 regions that are important in class II MHC binding and to determine whether the gp120 and class II MHC binding sites of CD4 are related. Class II MHC binding was abolished by mutations in each of the first three immunoglobulin-like domains of CD4. The gp120 binding could be abolished without affecting class II MHC binding and vice versa, although at least one mutation examined reduced both functions significantly. These findings indicate that, while there may be overlap between the gp120 and class II MHC binding sites of CD4, these sites are distinct and can be separated. Thus it should be possible to design CD4 analogs that can block HIV infectivity but intrinsically lack the ability to affect the normal immune response by binding to class II MHC molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lamarre, D -- Ashkenazi, A -- Fleury, S -- Smith, D H -- Sekaly, R P -- Capon, D J -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):743-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montreal, Quebec, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2549633" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antigens, Surface ; Binding Sites ; DNA, Recombinant ; HIV/*metabolism ; HIV Envelope Protein gp120 ; HLA-DP Antigens/immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; Hybridomas ; Mice ; Molecular Sequence Data ; Mutation ; Receptors, HIV ; Receptors, Virus/genetics/immunology/*metabolism ; Retroviridae Proteins/immunology/*metabolism ; Rosette Formation ; Structure-Activity Relationship ; T-Lymphocytes/immunology/metabolism ; Transfection
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-31
    Description: C/EBP is a rat liver nuclear protein capable of sequence-specific interaction with DNA. The DNA sequences to which C/EBP binds in vitro have been implicated in the control of messenger RNA synthesis. It has therefore been predicted that C/EBP will play a role in regulating gene expression in mammalian cells. The region of the C/EBP polypeptide required for direct interaction with DNA has been identified and shown to bear amino acid sequence relatedness with the product of the myc, fos, and jun proto-oncogenes. The arrangement of these related amino acid sequences led to the prediction of a new structural motif, termed the "leucine zipper," that plays a role in facilitating sequence-specific interaction between protein and DNA. Experimental tests now provide support for the leucine zipper hypothesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landschulz, W H -- Johnson, P F -- McKnight, S L -- New York, N.Y. -- Science. 1989 Mar 31;243(4899):1681-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Carnegie Institution of Washington, Department of Embryology, Baltimore, MD 21210.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2494700" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; CCAAT-Enhancer-Binding Proteins ; Cross-Linking Reagents ; DNA/*metabolism ; Glutaral ; Leucine ; Liver/*analysis ; Macromolecular Substances ; Molecular Weight ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Protein Conformation ; Rats ; Repetitive Sequences, Nucleic Acid ; Structure-Activity Relationship
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  • 12
    Publication Date: 1989-05-26
    Description: Spondyloepiphyseal dysplasias (SED) are a heterogeneous group of inherited disorders characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems. Evidence has suggested that SED may result from structural defects in type II collagen. To confirm the validity of this hypothesis, the structure of the "candidate" type II collagen gene (COL2A1) has been directly examined in a relatively large SED family. Coarse scanning of the gene by Southern blot hybridization identified an abnormal restriction pattern in one of the affected members of the kindred. Analysis of selected genomic fragments, amplified by the polymerase chain reaction, precisely localized the molecular defect and demonstrated that all affected family members carried the same heterozygous single-exon deletion. As a consequence of the mutation, nearly 90 percent of the assembled type II collagen homotrimers are expected to contain one or more procollagen subunits harboring an interstitial deletion of 36 amino acids in the triple helical domain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, B -- Vissing, H -- Ramirez, F -- Rogers, D -- Rimoin, D -- AR-38648/AR/NIAMS NIH HHS/ -- HD-22657/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1989 May 26;244(4907):978-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, State University of New York Health Science Center, Brooklyn 11203.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2543071" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Child, Preschool ; Chromosome Deletion ; Collagen/*genetics ; DNA Restriction Enzymes ; DNA-Directed DNA Polymerase ; Exons ; Female ; Gene Amplification ; Humans ; Macromolecular Substances ; Male ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Osteochondrodysplasias/*genetics ; Pedigree ; Procollagen/genetics
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  • 13
    Publication Date: 1989-01-27
    Description: Embryonal carcinoma (EC) cell lines are models for early cells in mouse embryogenesis. A 300-base pair fragment of the heavy chain enhancer was inactive in F9 EC cells, unlike in other nonlymphoid cells where it has significant activity. Alterations of the octamer motif increased enhancer activity. Nuclear extracts from F9 cells contained an octamer binding protein (NF-A3) that was unique to EC cells; the amount of NF-A3 decreased upon differentiation. It is proposed that NF-A3 represses specific regulatory sequences that contain the octamer motif. Thus, the same DNA sequence mediates either negative or positive transcriptional effects, depending on the cell type.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lenardo, M J -- Staudt, L -- Robbins, P -- Kuang, A -- Mulligan, R C -- Baltimore, D -- CA 01074/CA/NCI NIH HHS/ -- HD0063/HD/NICHD NIH HHS/ -- HL37569/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Jan 27;243(4890):544-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2536195" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bucladesine/pharmacology ; Cell Differentiation ; DNA/metabolism ; Embryonal Carcinoma Stem Cells ; *Enhancer Elements, Genetic ; Immunoglobulin Heavy Chains/*genetics ; Macromolecular Substances ; Mice ; Mutation ; Neoplastic Stem Cells/*metabolism ; RNA, Messenger/biosynthesis ; Regulatory Sequences, Nucleic Acid ; Repressor Proteins/genetics ; Transcription, Genetic ; Transfection ; Tretinoin/pharmacology ; Tumor Cells, Cultured
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-10-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Linsk, R -- Gottesman, M -- Pernis, B -- New York, N.Y. -- Science. 1989 Oct 13;246(4927):261.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2799388" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; Genes, MHC Class I/physiology ; Immune Tolerance/*genetics ; Organ Specificity/*genetics ; Thymus Gland/physiology
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  • 15
    Publication Date: 1989-04-21
    Description: Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindstein, T -- June, C H -- Ledbetter, J A -- Stella, G -- Thompson, C B -- New York, N.Y. -- Science. 1989 Apr 21;244(4902):339-43.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2540528" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, CD28 ; Antigens, CD3 ; Antigens, Differentiation, T-Lymphocyte/immunology ; Colony-Stimulating Factors/genetics ; Drug Stability ; Gene Expression Regulation ; Granulocyte-Macrophage Colony-Stimulating Factor ; Growth Substances/genetics ; Interferon-gamma/genetics ; Interleukin-2/genetics ; *Lymphocyte Activation ; Lymphokines/*genetics ; RNA, Messenger/genetics/*metabolism ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology ; Transcription, Genetic ; Tumor Necrosis Factor-alpha/genetics
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  • 16
    Publication Date: 1989-08-04
    Description: Complementary DNA clones, encoding the LH-hCG (luteinizing hormone-human choriogonadotropic hormone) receptor were isolated by screening a lambda gt11 library with monoclonal antibodies. The primary structure of the protein was deduced from the DNA sequence analysis; the protein contains 696 amino acids with a putative signal peptide of 27 amino acids. Hydropathy analysis suggests the existence of seven transmembrane domains that show homology with the corresponding regions of other G protein-coupled receptors. Three other types of clones corresponding to shorter proteins were observed, in which the putative transmembrane domain was absent. These probably arose through alternative splicing. RNA blot analysis showed similar patterns in testis and ovary with a major RNA of 4700 nucleotides and several minor species. The messenger RNA was expressed in COS-7 cells, yielding a protein that bound hCG with the same affinity as the testicular receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loosfelt, H -- Misrahi, M -- Atger, M -- Salesse, R -- Vu Hai-Luu Thi, M T -- Jolivet, A -- Guiochon-Mantel, A -- Sar, S -- Jallal, B -- Garnier, J -- New York, N.Y. -- Science. 1989 Aug 4;245(4917):525-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut National de la Sante et de la Recherche Medicale Unite 135, Hopital de Bicetre, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2502844" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Membrane/*metabolism ; *Cloning, Molecular ; DNA/*genetics ; Female ; GTP-Binding Proteins/metabolism ; Male ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Ovary/analysis ; Protein Sorting Signals/genetics ; RNA, Messenger/analysis/genetics ; Receptors, LH/*genetics/metabolism ; Sequence Homology, Nucleic Acid ; Swine ; Testis/analysis ; Tissue Distribution
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  • 17
    Publication Date: 1989-08-18
    Description: Keratinocyte growth factor (KGF) is a human mitogen that is specific for epithelial cells. The complementary DNA sequence of KGF demonstrates that it is a member of the fibroblast growth factor family. The KGF transcript was present in stromal cells derived from epithelial tissues. By comparison with the expression of other epithelial cell mitogens, only KGF, among known human growth factors, has the properties of a stromal mediator of epithelial cell proliferation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Finch, P W -- Rubin, J S -- Miki, T -- Ron, D -- Aaronson, S A -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):752-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2475908" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Division ; Codon ; DNA/genetics/isolation & purification ; Epithelial Cells ; Epithelium/analysis/metabolism ; Fibroblast Growth Factor 10 ; Fibroblast Growth Factor 7 ; *Fibroblast Growth Factors/genetics ; Fibroblasts/metabolism ; Gene Expression Regulation ; Growth Substances/*genetics/physiology ; Humans ; Mesoderm/metabolism ; Mice ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Oligonucleotide Probes ; RNA/analysis ; Sequence Homology, Nucleic Acid ; Skin/analysis ; Tissue Distribution ; Transcription, Genetic
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J L -- New York, N.Y. -- Science. 1989 Jun 16;244(4910):1254, 1256.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2734608" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/*prevention & control ; Animals ; HIV Antibodies/*biosynthesis ; HIV-1/*immunology ; Humans ; Mutation ; Pan troglodytes ; Vaccines, Inactivated/immunology ; Viral Vaccines/*immunology
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J L -- New York, N.Y. -- Science. 1989 May 12;244(4905):654-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2566202" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/*genetics/pathology ; Female ; *Gene Amplification ; Gene Expression Regulation ; Humans ; Lymph Nodes/pathology ; *Neoplasm Recurrence, Local ; Ovarian Neoplasms/*genetics ; Prognosis ; Proto-Oncogene Proteins/*genetics ; *Proto-Oncogenes ; Receptor, ErbB-2
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, J L -- New York, N.Y. -- Science. 1989 Mar 31;243(4899):1664-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2494699" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*etiology/genetics/pathology ; *Amyloid/genetics/physiology ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Gene Expression Regulation ; Humans ; Interleukin-1/physiology ; Nerve Growth Factors/physiology ; Neurons/pathology ; Protease Inhibitors ; *Protein Precursors/genetics/physiology
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  • 21
    Publication Date: 1989-12-08
    Description: The fragile X syndrome is the most common cause of familial mental retardation. Genetic counseling and gene isolation are hampered by a lack of DNA markers close to the disease locus. Two somatic cell hybrids that each contain a human X chromosome with a breakpoint close to the fragile X locus have been characterized. A new DNA marker (DXS296) lies between the chromosome breakpoints and is the closest marker to the fragile X locus yet reported. The Hunter syndrome gene, which causes iduronate sulfatase deficiency, is located at the X chromosome breakpoint that is distal to this new marker, thus localizing the Hunter gene distal to the fragile X locus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suthers, G K -- Callen, D F -- Hyland, V J -- Kozman, H M -- Baker, E -- Eyre, H -- Harper, P S -- Roberts, S H -- Hors-Cayla, M C -- Davies, K E -- New York, N.Y. -- Science. 1989 Dec 8;246(4935):1298-300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Histopathology, Adelaide Children's Hospital, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2573953" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosome Mapping ; Female ; Fragile X Syndrome/*genetics ; Genetic Counseling ; *Genetic Linkage ; *Genetic Markers ; Genomic Library ; Humans ; Hybrid Cells ; Likelihood Functions ; Mice ; Mucopolysaccharidosis II/genetics ; Mutation ; Nucleic Acid Hybridization ; Polymorphism, Restriction Fragment Length ; Sex Chromosome Aberrations/*genetics ; Translocation, Genetic
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  • 22
    Publication Date: 1989-03-31
    Description: The tpa-1 gene mediates the action of tumor-promoting phorbol esters in the nematode Caenorhabditis elegans. A genomic fragment that constitutes a portion of the tpa-1 gene was cloned by Tc1 transposon tagging and was used as a probe to screen a nematode complementary DNA library. One of the isolated complementary DNA clones had a nucleotide sequence that predicts a polypeptide of 526 amino acids. The predicted amino acid sequence revealed that the predicted tpa-1 protein sequence is highly similar to protein kinase C molecules from various animals, including man.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabuse, Y -- Nishiwaki, K -- Miwa, J -- New York, N.Y. -- Science. 1989 Mar 31;243(4899):1713-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fundamental Research Laboratories, NEC Corporation, Kawasaki, Kanagawa, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2538925" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Caenorhabditis/*drug effects/genetics ; Cloning, Molecular ; Codon ; DNA/genetics ; DNA Restriction Enzymes ; Drug Resistance/genetics ; Genetic Markers ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Phenotype ; Phorbol Esters/*pharmacology ; Protein Kinase C/*genetics ; Sequence Homology, Nucleic Acid
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  • 23
    Publication Date: 1989-10-27
    Description: Allele loss is a hallmark of chromosome regions harboring recessive oncogenes. Lung cancer frequently demonstrates loss of heterozygosity on 17p. Recent evidence suggests that the p53 gene located on 17p13 has many features of such an antioncogene. The p53 gene was frequently mutated or inactivated in all types of human lung cancer. The genetic abnormalities of p53 include gross changes such as homozygous deletions and abnormally sized messenger RNAs along with a variety of point or small mutations, which map to the p53 open reading frame and change amino acid sequence in a region highly conserved between mouse and man. In addition, very low or absent expression of p53 messenger RNA in lung cancer cell lines compared to normal lung was seen. These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, T -- Nau, M M -- Chiba, I -- Birrer, M J -- Rosenberg, R K -- Vinocour, M -- Levitt, M -- Pass, H -- Gazdar, A F -- Minna, J D -- New York, N.Y. -- Science. 1989 Oct 27;246(4929):491-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD 20814.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2554494" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Carcinoid Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Small Cell/genetics ; Chromosomes, Human, Pair 17 ; DNA, Neoplasm/genetics ; Gene Amplification ; Humans ; Lung Neoplasms/*genetics ; Mutation ; Oncogene Proteins/*genetics ; Phosphoproteins/*genetics ; RNA, Messenger/genetics ; RNA, Neoplasm/genetics ; Ribonucleases ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53
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  • 24
    Publication Date: 1989-01-06
    Description: The temperature dependences of the reduction potentials (E degrees') of wild-type human myoglobin (Mb) and three site-directed mutants have been measured by the use of thin-layer spectroelectrochemistry. Residue Val68, which is in van der Waals contact with the heme in Mb, has been replaced by Glu, Asp, and Asn. The changes in E degrees' and the standard entropy (delta S degrees') and enthalpy (delta H degrees') of reduction in the mutant proteins were determined relative to values for wild type; the change in E degrees' at 25 degrees C was about -200 millivolts for the Glu and Asp mutants, and about -80 millivolts for the Asn mutant. At pH 7.0, reduction of Fe(III) to Fe(II) in the Glu and Asp mutants is accompanied by uptake of a proton by the protein. These studies demonstrate that Mb can tolerate substitution of a buried hydrophobic group by potentially charged and polar residues and that such amino acid replacements can lead to substantial changes in the redox thermodynamics of the protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Varadarajan, R -- Zewert, T E -- Gray, H B -- Boxer, S G -- DK 19038/DK/NIDDK NIH HHS/ -- GM 27738/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jan 6;243(4887):69-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Stanford University, CA 94305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2563171" target="_blank"〉PubMed〈/a〉
    Keywords: Asparagine ; Aspartic Acid ; Glutamates ; Glutamic Acid ; Heme/metabolism ; Humans ; Mutation ; Myoglobin/*metabolism ; Oxidation-Reduction ; Protein Conformation ; Recombinant Proteins/*metabolism ; Thermodynamics ; Valine
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  • 25
    Publication Date: 1989-02-03
    Description: The biological effects of ras oncogene activation in B cells were studied by using amphotropic retroviral vectors to introduce H- or N-ras oncogenes into human B lymphoblasts immortalized by Epstein-Barr virus. Expression of both H- and N-ras oncogenes led to malignant transformation of these cells, as shown by clonogenicity in semisolid media and tumorigenicity in immunodeficient mice. In addition, terminal differentiation into plasma cells was detectable as specific changes in morphology, immunoglobulin secretion, and cell surface antigen expression. This combined effect, promoting growth and differentiation in human lymphoblasts, represents a novel biological action of ras oncogenes and has implications for the pathogenesis of terminally differentiated B-lymphoid malignancies such as multiple myeloma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seremetis, S -- Inghirami, G -- Ferrero, D -- Newcomb, E W -- Knowles, D M -- Dotto, G P -- Dalla-Favera, R -- CA-37165/CA/NCI NIH HHS/ -- CA49236/CA/NCI NIH HHS/ -- EY 06337/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 3;243(4891):660-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University, NY 10016.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2536954" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/metabolism/*pathology ; Cell Differentiation ; *Cell Transformation, Neoplastic ; *Cell Transformation, Viral ; DNA Replication ; Flow Cytometry ; Fluorescent Antibody Technique ; Gene Expression Regulation ; *Genes, ras ; *Herpesvirus 4, Human ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental/etiology ; Phenotype ; Plasma Cells/*pathology
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  • 26
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-11-03
    Description: An 88-base pair fragment in the core promoter of the human hepatitis B virus (HBV) contains a functional promoter and a strong liver-specific enhancer. This enhancer functions in human hepatoma cells, where it is much more active than the previously described HBV enhancer in stimulating expression of the linked bacterial chloramphenicol acetyltransferase gene expressed from heterologous promoters. Studies of the role of this enhancer-promoter in HBV may help to clarify mechanisms of gene expression in cells infected with HBV and the role of the virus in the pathogenesis of hepatitis and hepatocellular carcinoma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yee, J K -- New York, N.Y. -- Science. 1989 Nov 3;246(4930):658-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, School of Medicine, 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/2554495" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Chloramphenicol O-Acetyltransferase/genetics ; Chromosome Deletion ; *Enhancer Elements, Genetic ; *Genes, Viral ; Hepatitis B virus/*genetics ; Liver/*metabolism ; Molecular Sequence Data ; Mutation ; *Promoter Regions, Genetic ; Simplexvirus/enzymology/genetics ; Thymidine Kinase/genetics ; Transcription, Genetic ; Transfection ; Viral Structural Proteins/genetics
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-11-24
    Description: Parasitic protozoans and helminths pose considerable medical as well as scientific challenges. Investigations of the complex and very different life cycles of these organisms, their adaptation to the obligate parasitic mode of life, and their ability to face the hostile host environment have resulted in many exciting discoveries. Invasion of host erythrocytes by plasmodial sporozoites and intact skin by schistosomal cercariae are outlined as examples of the elaborate mechanisms of parasitism. Isolation and characterization of single protective antigens or subunit vaccines from these two organisms are examined as models for vaccine development. Finally, developments in exploring gene regulation in protozoans and free and parasitic nematodes are briefly outlined.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mahmoud, A A -- New York, N.Y. -- Science. 1989 Nov 24;246(4933):1015-22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2686024" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Eukaryota/genetics/pathogenicity/*physiology ; Gene Expression Regulation ; Helminthiasis/*immunology ; Helminths/genetics/pathogenicity/*physiology ; Humans ; Molecular Sequence Data ; Protozoan Infections/*immunology
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  • 28
    Publication Date: 1989-04-28
    Description: Mice transgenic for a hybrid gene containing the liver promoter of the mouse amylase gene (Amy-1a) fused to the SV40 tumor antigen coding region unexpected developed malignant brown adipose tissue tumors (malignant hibernomas). Expression of the alpha-amylase gene had previously been thought to be confined to the liver parotid, and pancreas; however, analysis of white and brown adipose tissue from nontransgenic mice revealed expression of the endogenous Amy-1a gene in these tissues. Gene constructs driven by the Amy-1a liver promoter thus provide a means of targeting gene expression to the adipocyte cell lineage in transgenic mice. Moreover the high frequency of metastases in the liver, lungs, spleen, heart, and adrenals of these mice provides an experimental system in which to study the development of disseminated malignancy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fox, N -- Crooke, R -- Hwang, L H -- Schibler, U -- Knowles, B B -- Solter, D -- CA-10815/CA/NCI NIH HHS/ -- CA-18470/CA/NCI NIH HHS/ -- CA-21124/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):460-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wistar Institute, Philadelphia, PA 19104.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2785714" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism/pathology ; *Adipose Tissue, Brown/metabolism/pathology ; Animals ; Antigens, Polyomavirus Transforming/*genetics ; Cloning, Molecular ; Gene Expression Regulation ; Liver/metabolism ; Mice ; Mice, Transgenic ; Neoplasm Metastasis ; Neoplasms, Experimental/*genetics/pathology ; Nucleic Acid Hybridization ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Tissue Distribution ; Transcription, Genetic ; alpha-Amylases/*genetics
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  • 29
    Publication Date: 1989-07-21
    Description: Mammalian glucocorticoid receptors enhance transcription from linked promoters by binding to glucocorticoid response element (GRE) DNA sequences. Understanding the mechanism of receptor action will require biochemical studies with purified components. Enhancement was observed in vitro with derivatives of the receptor that were expressed in Escherichia coli, purified, and added to a cell-free extract from Drosophila embryo nuclei. Transcription from promoters linked to one or multiple GREs was selectively enhanced by as much as six times. The effect was weaker with only one GRE, and enhancement was abolished by a point mutation that inactivates the GRE in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Freedman, L P -- Yoshinaga, S K -- Vanderbilt, J N -- Yamamoto, K R -- New York, N.Y. -- Science. 1989 Jul 21;245(4915):298-301.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2473529" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cloning, Molecular ; DNA/genetics/metabolism ; Drosophila melanogaster ; Mutation ; Promoter Regions, Genetic ; RNA/biosynthesis ; Rats ; Receptors, Glucocorticoid/*genetics/isolation & purification/metabolism ; Templates, Genetic ; *Transcription, Genetic
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  • 30
    Publication Date: 1989-10-27
    Description: Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pizza, M -- Covacci, A -- Bartoloni, A -- Perugini, M -- Nencioni, L -- De Magistris, M T -- Villa, L -- Nucci, D -- Manetti, R -- Bugnoli, M -- New York, N.Y. -- Science. 1989 Oct 27;246(4929):497-500.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sclavo Research Center, Siena, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2683073" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Genetic Techniques ; Mice ; Mice, Inbred BALB C ; Mutation ; *Pertussis Toxin ; Pertussis Vaccine/*toxicity ; Rabbits ; Vaccines, Synthetic/toxicity ; Virulence Factors, Bordetella/genetics/immunology/*toxicity
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  • 31
    Publication Date: 1989-05-05
    Description: Promonocytic (U1) and T lymphocytic (ACH-2) cell lines chronically infected with human immunodeficiency virus type 1 (HIV-1) constitutively express low levels of virus, but expression can be induced by phorbol esters and cytokines. Whereas ACH-2 cells produce infectious virions, U1 cells produce defective, noninfectious particles. Although 3'-azido-3'-deoxythimidine (AZT) prevented acute HIV infection of susceptible cells, it did not prevent the induction of HIV expression in the infected cell lines. In contrast, interferon alpha (IFN-alpha) inhibited the release of reverse transcriptase and viral antigens into the culture supernatant after phorbol ester stimulation of both cell lines. Further, IFN-alpha suppressed the production or release (or both) of whole HIV virions, but had no effect on the amount of cell-associated viral proteins. Also, after phorbol ester stimulation of ACH-2 cells, IFN-alpha reduced the number of infectious viral particles secreted into the culture supernatant, but had no effect on the infectivity of cell-associated virus. These findings lend support to the combined use of antiviral agents that have action at both the early (AZT) and the late (IFN-alpha) stages of HIV replication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poli, G -- Orenstein, J M -- Kinter, A -- Folks, T M -- Fauci, A S -- New York, N.Y. -- Science. 1989 May 5;244(4904):575-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2470148" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/therapy ; Cell Line ; Cell Membrane/microbiology ; Drug Therapy, Combination ; Gene Expression Regulation ; HIV-1/drug effects/*physiology/ultrastructure ; Immunoblotting ; Interferon Type I/administration & dosage/*pharmacology ; Microscopy, Electron ; Monocytes/microbiology ; RNA-Directed DNA Polymerase/metabolism ; Recombinant Proteins ; T-Lymphocytes/microbiology ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription, Genetic ; Vacuoles/microbiology ; Virion/drug effects/physiology/ultrastructure ; Virus Replication/*drug effects ; Zidovudine/administration & dosage/*pharmacology
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  • 32
    Publication Date: 1989-02-03
    Description: The nitrogen regulatory (NtrC) protein of enteric bacteria, which binds to sites that have the properties of transcriptional enhancers, is known to activate transcription by a form of RNA polymerase that contains the NtrA protein (sigma 54) as sigma factor (referred to as sigma 54-holoenzyme). In the presence of adenosine triphosphate, the NtrC protein catalyzes isomerization of closed recognition complexes between sigma 54-holoenzyme and the glnA promoter to open complexes in which DNA in the region of the transcription start site is locally denatured. NtrC is not required subsequently for maintenance of open complexes or initiation of transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popham, D L -- Szeto, D -- Keener, J -- Kustu, S -- GM38361/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 3;243(4891):629-35.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, Berkley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2563595" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/analogs & derivatives/metabolism/pharmacology ; *Bacterial Proteins ; Base Sequence ; Binding Sites ; DNA, Bacterial/metabolism ; DNA-Binding Proteins/*metabolism ; DNA-Directed RNA Polymerases/metabolism ; Deoxyribonuclease I ; *Enhancer Elements, Genetic ; Glutamate-Ammonia Ligase/genetics ; Heparin/pharmacology ; Molecular Sequence Data ; Mutation ; PII Nitrogen Regulatory Proteins ; Phosphorylation ; Promoter Regions, Genetic ; Salmonella typhimurium/*genetics ; Sigma Factor/metabolism ; *Trans-Activators ; Transcription Factors ; *Transcription, Genetic
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-06-02
    Description: Specialized regions of muscle fibers may result from differential gene expression within a single fiber. In order to investigate the range of action of individual nuclei in multinucleated myotubes, C2 myoblasts were transfected to obtain stable cell lines that express a reporter protein that is targeted to the nucleus. Hybrid myotubes were then formed containing one or a few transfected nuclei as well as a large number of nuclei from the parental strain. In order to determine how far the products of a single nucleus extend, transfected nuclei were labeled with [3H]thymidine before fusion and the myotubes were stained to identify the reporter protein. In such myotubes the fusion protein was not confined to its nucleus of origin, but was restricted to nearby nuclei.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ralston, E -- Hall, Z W -- NS 20107/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jun 2;244(4908):1066-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, School of Medicine, University of California, San Francisco 94143-0444.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2543074" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Nucleus/*metabolism ; Cloning, Molecular ; Cytoplasm/metabolism ; Enhancer Elements, Genetic ; Escherichia coli/genetics ; Fluorescent Antibody Technique ; Gene Expression Regulation ; Globins/genetics ; Mice ; Muscle Proteins/*genetics/metabolism ; Muscles/*ultrastructure ; Plasmids ; Promoter Regions, Genetic ; Receptors, Glucocorticoid/genetics ; Simian virus 40/genetics ; *Transfection ; beta-Galactosidase/genetics
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-10-27
    Description: Expression of the c-myc oncogene is deregulated in a variety of malignancies. Rearrangement and mutation of the c-myc locus is a characteristic feature of human Burkitt's lymphoma. Whether deregulation is solely a result of mutation of c-myc or whether it is influenced by the transformed B cell context has not been determined. A translocated and mutated allele of c-myc was stably transfected into fibroblasts. The rearranged allele was expressed indistinguishably from a normal c-myc gene: it had serum-regulated expression, was transcribed with normal promoter preference, and was strongly attenuated. Thus mutations by themselves are insufficient to deregulate c-myc transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richman, A -- Hayday, A -- 40364/PHS HHS/ -- GM 07499/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Oct 27;246(4929):494-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biology Department, Yale University, New Haven, CT 06511.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2683072" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Burkitt Lymphoma/genetics ; Cell Line ; Fibroblasts/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Oncogenes/*genetics ; Proto-Oncogene Proteins/biosynthesis/*genetics ; Proto-Oncogene Proteins c-myc ; *Transfection ; Translocation, Genetic
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  • 35
    Publication Date: 1989-06-23
    Description: Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the ob/ob, db/db, and monosodium glutamate (MSG)-injected mouse and the fa/fa rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, B S -- Cook, K S -- Yaglom, J -- Groves, D L -- Volanakis, J E -- Damm, D -- White, T -- Spiegelman, B M -- DK31403/DK/NIDDK NIH HHS/ -- DK34605/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1989 Jun 23;244(4911):1483-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2734615" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Complement Activating Enzymes/*metabolism ; Complement Factor D/*metabolism ; Complement Pathway, Alternative ; Cricetinae ; DNA/genetics ; Gene Expression Regulation ; Humans ; Immunoblotting ; Mice ; Molecular Sequence Data ; Obesity/genetics/*immunology/metabolism ; RNA, Messenger/metabolism ; Recombinant Proteins ; Serine Endopeptidases/genetics/isolation & purification/*metabolism ; Substrate Specificity ; Transfection
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  • 36
    Publication Date: 1989-03-10
    Description: An analysis of the aminoacylation kinetics of unmodified yeast tRNAPhe mutants revealed that five single-stranded nucleotides are important for its recognition by yeast phenylalanyl-tRNA synthetase, provided they were positioned correctly in a properly folded tRNA structure. When four other tRNAs were changed to have these five nucleotides, they became near-normal substrates for the enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sampson, J R -- DiRenzo, A B -- Behlen, L S -- Uhlenbeck, O C -- GM 37552/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 10;243(4896):1363-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2646717" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acyl-tRNA Synthetases/*metabolism ; Base Sequence ; Escherichia coli/genetics ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Phenylalanine-tRNA Ligase/*metabolism ; Plants/genetics ; RNA, Transfer, Amino Acid-Specific/*genetics ; RNA, Transfer, Phe/*genetics/metabolism ; Schizosaccharomyces/genetics ; Transcription, Genetic ; Triticum/genetics
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-12-15
    Description: Tumor suppressor genes are wild-type alleles of genes that play regulatory roles in cell proliferation, differentiation, and other cellular and systemic processes. It is their loss or inactivation that is oncogenic. The first evidence of tumor suppressor genes appeared in the early 1970s, but only within the past few years has a wealth of new information illuminated the central importance of these genes. Two or more different suppressor genes may be inactivated in the same tumors, and the same suppressors may be inactive in different tumor types (for example, lung, breast, and colon). The suppressor genes already identified are involved in cell cycle control, signal transduction, angiogenesis, and development, indicating that they contribute to a broad array of normal and tumor-related functions. It is proposed that tumor suppressor genes provide a vast untapped resource for anticancer therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sager, R -- New York, N.Y. -- Science. 1989 Dec 15;246(4936):1406-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2574499" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Cell Differentiation ; Cell Division ; Cell Transformation, Neoplastic/genetics ; Chromosome Aberrations ; Cloning, Molecular ; Eye Neoplasms/genetics ; Heterozygote ; Humans ; Hybrid Cells ; Kidney Neoplasms/genetics ; Mutation ; Neoplasms/*genetics ; Oncogene Proteins/genetics ; Phosphoproteins/genetics ; Polymorphism, Restriction Fragment Length ; Retinoblastoma/genetics ; Suppression, Genetic/*genetics ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 ; Wilms Tumor/genetics
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  • 38
    Publication Date: 1989-02-24
    Description: In Drosophila, five "terminal" polarity genes must be active in females in order for them to produce embryos with normal anterior and posterior ends. Hypoactivity mutations in one such gene, torso, result in the loss of the most posterior domain of fushi tarazu expression and the terminal cuticular structures. In contrast, a torso hyperactivity mutation causes the loss of central fushi tarazu expression and central cuticular structures. Cytoplasmic leakage, transplantation, and temperature-shift experiments suggest that the latter effect is caused by abnormal persistence of the torso product in the central region of the embryo during early development. Thus, the amount and timing of torso activity is key to distinguishing the central and terminal regions of the embryo. Mutations in the tailless terminal gene act as dominant maternal suppressors of the hyperactive torso allele, indicating that the torso product acts through, or in concert with, the tailless product.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strecker, T R -- Halsell, S R -- Fisher, W W -- Lipshitz, H D -- GM07616/GM/NIGMS NIH HHS/ -- HD23099/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 24;243(4894 Pt 1):1062-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2922596" target="_blank"〉PubMed〈/a〉
    Keywords: Abdomen ; Alleles ; Animals ; Cytoplasm/physiology ; Drosophila/anatomy & histology/embryology/*genetics ; Female ; Gene Expression Regulation ; Mutation ; Phenotype ; Suppression, Genetic ; Thorax
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-05-26
    Description: T cell receptors are the antigen-recognizing elements found on the effector cells of the immune system. Two isotypes have been discovered, TCR-gamma delta and TCR-alpha beta, which appear in that order during ontogeny. The maturation of prothymocytes that colonize the thymic rudiment at defined gestational stages occurs principally within the thymus, although some evidence for extrathymic maturation also exists. The maturation process includes the rearrangement and expression of the T cell receptor genes. Determination of these mechanisms, the lineages of the cells, and the subsequent thymic selection that results in self-tolerance is the central problem in developmental immunology and is important for the understanding of autoimmune diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strominger, J L -- New York, N.Y. -- Science. 1989 May 26;244(4907):943-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2658058" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Differentiation, T-Lymphocyte/analysis ; Gene Expression Regulation ; Humans ; Receptors, Antigen, T-Cell/genetics/immunology/*physiology ; T-Lymphocytes/*immunology ; Thymus Gland/embryology/*growth & development/immunology
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-11-17
    Description: The proposal that the absorption maximum of the visual pigments is governed by interaction of the 11-cis-retinal chromophore with charged carboxylic acid side chains in the membrane-embedded regions of the proteins has been tested by mutating five Asp and Glu residues thought to be buried in rhodopsin. Changing Glu113 to Gln causes a dramatic shift in the absorption maximum from 500 nanometers to 380 nanometers, a decrease in the pKa (acidity constant) of the protonated Schiff base of the chromophore to about 6, and a greatly increased reactivity with hydroxylamine. Thus Glu113 appears to be the counterion to the protonated Schiff base. Wavelength modulation in visual pigments apparently is not governed by electrostatic interaction with carboxylate residues, other than the counterion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhukovsky, E A -- Oprian, D D -- 5T32 GM07596-11/GM/NIGMS NIH HHS/ -- EY07965/EY/NEI NIH HHS/ -- R01 EY007965/EY/NEI NIH HHS/ -- S07 RR07044/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1989 Nov 17;246(4932):928-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Brandeis University, Waltham, MA 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2573154" target="_blank"〉PubMed〈/a〉
    Keywords: *Aspartic Acid ; Glutamates ; Glutamic Acid ; Hydrogen-Ion Concentration ; Hydroxylamine ; Hydroxylamines/pharmacology ; Models, Molecular ; Mutation ; Protein Conformation ; Retinal Pigments/*metabolism ; Retinaldehyde/*metabolism ; Retinoids/*metabolism ; Rhodopsin/genetics/*metabolism ; Schiff Bases ; Spectrophotometry
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-06-16
    Description: Current therapies for most human genetic diseases are inadequate. In response to the need for effective treatments, modern molecular genetics is providing tools for an unprecedented new approach to disease treatment through an attack directly on mutant genes. Recent results with several target organs and gene transfer techniques have led to broad medical and scientific acceptance of the feasibility of this "gene therapy" concept for disorders of the bone marrow, liver, and central nervous system; some kinds of cancer; and deficiencies of circulating enzymes, hormones, and coagulation factors. The most well-developed models involve alteration of mutant target genes by gene transfer with recombinant pathogenic viruses in order to express new genetic information and to correct disease phenotypes--the conversion of the swords of pathology into the plowshares of therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Friedmann, T -- New York, N.Y. -- Science. 1989 Jun 16;244(4910):1275-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatrics, School of Medicine, 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/2660259" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow/physiology ; Brain/physiology ; Ethics, Medical ; Gene Expression Regulation ; Genetic Diseases, Inborn ; Genetic Therapy/*methods/trends ; Genetic Vectors ; Humans ; Liver/physiology ; Neoplasms/genetics ; Risk Assessment ; Transfection
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  • 42
    Publication Date: 1989-10-27
    Description: Activation of protein kinase C is thought to require association of the kinase with the cell membrane. It has been assumed that cellular substrates for the kinase must likewise be associated with membranes, and previous studies with membrane-associated myristoylated proteins have supported this view. It is now shown that a mutation that prevents the normal amino-terminal myristoylation of a prominent cellular substrate of protein kinase C, and appears to prevent its membrane association, does not prevent the normal phosphorylation of this protein in intact cells in response to phorbol esters. Thus, membrane association may not be required in order for protein kinase C substrates to undergo phosphorylation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graff, J M -- Gordon, J I -- Blackshear, P J -- 2T32-GM 07171/GM/NIGMS NIH HHS/ -- AI27179/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1989 Oct 27;246(4929):503-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Laboratories, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2814478" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cells, Cultured ; Chickens ; Enzyme Activation ; *Intracellular Signaling Peptides and Proteins ; Membrane Proteins/metabolism ; Mutation ; Myristic Acid ; Myristic Acids ; Phosphorylation ; Protein Kinase C/*metabolism ; Proteins/*metabolism ; Substrate Specificity ; Transfection
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  • 43
    Publication Date: 1989-05-05
    Description: Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hatakeyama, M -- Tsudo, M -- Minamoto, S -- Kono, T -- Doi, T -- Miyata, T -- Miyasaka, M -- Taniguchi, T -- New York, N.Y. -- Science. 1989 May 5;244(4904):551-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Molecular and Cellular Biology, Osaka University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2785715" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; *Cloning, Molecular ; Cross-Linking Reagents ; DNA/*genetics/isolation & purification ; Fibroblasts/metabolism ; Gene Expression Regulation ; Humans ; Interleukin-2/metabolism ; Leukemia ; Molecular Sequence Data ; Nucleic Acid Hybridization ; RNA, Messenger/genetics ; Receptors, Interleukin-2/*genetics/metabolism ; Recombinant Proteins ; Sequence Homology, Nucleic Acid ; Signal Transduction ; Succinimides ; T-Lymphocytes/metabolism ; Transfection ; Tumor Cells, Cultured
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  • 44
    Publication Date: 1989-02-10
    Description: A genomic sequence and cloned complementary DNA has been identified for a novel receptor-like gene of the PDGF receptor/CSF1 receptor subfamily (platelet-derived growth factor receptor/colony-stimulating factor type 1 receptor). The gene recognized a 6.4-kilobase transcript that was coexpressed in normal human tissues with the 5.3-kilobase PDGF receptor messenger RNA. Introduction of complementary DNA of the novel gene into COS-1 cells led to expression of proteins that were specifically detected with antiserum directed against a predicted peptide. When the new gene was transfected into COS-1 cells, a characteristic pattern of binding of the PDGF isoforms was observed, which was different from the pattern observed with the known PDGF receptor. Tyrosine phosphorylation of the receptor in response to the PDGF isoforms was also different from the known receptor. The new PDGF receptor gene was localized to chromosome 4q11-4q12. The existence of genes encoding two PDGF receptors that interact in a distinct manner with three different PDGF isoforms likely confers considerable regulatory flexibility in the functional responses to PDGF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsui, T -- Heidaran, M -- Miki, T -- Popescu, N -- La Rochelle, W -- Kraus, M -- Pierce, J -- Aaronson, S -- New York, N.Y. -- Science. 1989 Feb 10;243(4892):800-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2536956" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Cells, Cultured ; *Chromosomes, Human, Pair 4 ; Cloning, Molecular ; DNA/genetics ; Gene Expression Regulation ; *Genes ; Humans ; Molecular Sequence Data ; Multigene Family ; Platelet-Derived Growth Factor/*physiology ; Protein-Tyrosine Kinases/genetics ; RNA, Messenger/genetics ; Receptors, Cell Surface/*genetics ; Receptors, Platelet-Derived Growth Factor ; Tissue Distribution
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  • 45
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-07-28
    Description: The cloning of genes encoding mammalian DNA binding transcription factors for RNA polymerase II has provided the opportunity to analyze the structure and function of these proteins. This review summarizes recent studies that define structural domains for DNA binding and transcriptional activation functions in sequence-specific transcription factors. The mechanisms by which these factors may activate transcriptional initiation and by which they may be regulated to achieve differential gene expression are also discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mitchell, P J -- Tjian, R -- New York, N.Y. -- Science. 1989 Jul 28;245(4916):371-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2667136" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Binding Sites ; Cloning, Molecular ; DNA-Binding Proteins/*genetics/metabolism ; Gene Expression Regulation ; Molecular Sequence Data ; Protein Processing, Post-Translational ; RNA Polymerase II/*genetics/metabolism ; Repetitive Sequences, Nucleic Acid ; Transcription Factors/*genetics/metabolism ; *Transcription, Genetic
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  • 46
    Publication Date: 1989-06-23
    Description: The multiprotein-DNA complexes that participate in bacteriophage lambda site-specific recombination were used to study the combined effect of protein-induced bending and protein-mediated looping of DNA. The protein integrase (Int) is a monomer with two autonomous DNA binding domains of different sequence specificity. Stimulation of Int binding and cleavage at the low affinity core-type DNA sites required interactions with the high affinity arm-type sites and depended on simultaneous binding of the sequence-specific DNA bending protein IHF (integration host factor). The bivalent DNA binding protein is positioned at high affinity sites and directed, by a DNA bending protein, to interactions with distant lower affinity sites. Assembly of this complex is independent of protein-protein interactions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892171/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892171/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moitoso de Vargas, L -- Kim, S -- Landy, A -- AI-13544/AI/NIAID NIH HHS/ -- GM-33928/GM/NIGMS NIH HHS/ -- R01 GM033928/GM/NIGMS NIH HHS/ -- R01 GM062723/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jun 23;244(4911):1457-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology and Medicine, Brown University, Providence, RI 02912.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2544029" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/metabolism/*pharmacology ; Bacteriophage lambda/enzymology/*genetics ; Binding Sites ; DNA Nucleotidyltransferases/*metabolism ; DNA Restriction Enzymes ; DNA Transposable Elements ; DNA, Bacterial/genetics/*metabolism ; DNA, Viral/genetics/*metabolism ; DNA-Binding Proteins/metabolism ; Integrases ; Integration Host Factors ; Mutation ; Nucleic Acid Conformation/*drug effects ; Recombination, Genetic
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  • 47
    Publication Date: 1989-10-13
    Description: Interleukin-1 (IL-1) is a major regulator of inflammation and immunity. IL-1 induces T lymphocyte growth by acting as a second signal (together with antigen) in enhancing the production of interleukin-2 (IL-2). An IL-1-responsive element in the promoter region of the human IL-2 gene was similar to the binding site for the transcription factor AP-1. IL-1 enhanced expression of c-jun messenger RNA, whereas the antigenic signal enhanced messenger RNA expression of c-fos. Thus, the two components of the AP-1 factor are independently regulated and the AP-1 factor may serve as a nuclear mediator for the many actions of IL-1 on cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Muegge, K -- Williams, T M -- Kant, J -- Karin, M -- Chiu, R -- Schmidt, A -- Siebenlist, U -- Young, H A -- Durum, S K -- 5-T32-CA-09140/CA/NCI NIH HHS/ -- AI-R01-23879/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1989 Oct 13;246(4927):249-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunoregulation, Program Resources Inc., Frederick, MD 21701.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2799385" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chloramphenicol O-Acetyltransferase/genetics ; Gene Expression Regulation ; Humans ; Interleukin-1/*physiology ; Interleukin-2/*genetics ; Mice ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-jun/*genetics ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection ; Tumor Cells, Cultured
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  • 48
    Publication Date: 1989-08-25
    Description: Blue cone monochromacy is a rare X-linked disorder of color vision characterized by the absence of both red and green cone sensitivities. In 12 of 12 families carrying this trait, alterations are observed in the red and green visual pigment gene cluster. The alterations fall into two classes. One class arose from the wild type by a two-step pathway consisting of unequal homologous recombination and point mutation. The second class arose by nonhomologous deletion of genomic DNA adjacent to the red and green pigment gene cluster. These deletions define a 579-base pair region that is located 4 kilobases upstream of the red pigment gene and 43 kilobases upstream of the nearest green pigment gene; this 579-base pair region is essential for the activity of both pigment genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nathans, J -- Davenport, C M -- Maumenee, I H -- Lewis, R A -- Hejtmancik, J F -- Litt, M -- Lovrien, E -- Weleber, R -- Bachynski, B -- Zwas, F -- New York, N.Y. -- Science. 1989 Aug 25;245(4920):831-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Wilmer Ophthalmologic Institute, 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/2788922" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Base Sequence ; Child ; Child, Preschool ; Chromosome Deletion ; Color Vision Defects/*genetics ; DNA/analysis ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Nucleic Acid Hybridization ; Retinal Pigments/genetics ; Thalassemia/genetics ; X Chromosome
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  • 49
    Publication Date: 1989-04-14
    Description: A new method has been developed that makes it possible to site-specifically incorporate unnatural amino acids into proteins. Synthetic amino acids were incorporated into the enzyme beta-lactamase by the use of a chemically acylated suppressor transfer RNA that inserted the amino acid in response to a stop codon substituted for the codon encoding residue of interest. Peptide mapping localized the inserted amino acid to a single peptide, and enough enzyme could be generated for purification to homogeneity. The catalytic properties of several mutants at the conserved Phe66 were characterized. The ability to selectively replace amino acids in a protein with a wide variety of structural and electronic variants should provide a more detailed understanding of protein structure and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Noren, C J -- Anthony-Cahill, S J -- Griffith, M C -- Schultz, P G -- New York, N.Y. -- Science. 1989 Apr 14;244(4901):182-8.〈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/2649980" target="_blank"〉PubMed〈/a〉
    Keywords: *Amino Acids ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli/enzymology ; Mutation ; Protein Biosynthesis ; *Proteins ; RNA, Transfer/isolation & purification ; beta-Lactamases
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  • 50
    Publication Date: 1989-12-22
    Description: Granulocyte and natural killer (NK) cell Fc receptors for immunoglobulin G (CD16) differ in only a few amino acids, yet have phosphatidylinositol glycan (PIG) or polypeptide membrane anchors, respectively. Mutagenesis shows that anchoring is regulated by a serine residue near the PIG anchor attachment site in the extracellular domain. The NK cell isoform was not expressed on the surface of COS cells unless cotransfected with a subunit that was expressed in NK cells and that was identical to the gamma subunit of the high affinity IgE Fc receptor (Fc epsilon RI). However, the CD16 sequence and not expression of the gamma subunit is dominant in regulating PIG reanchoring.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hibbs, M L -- Selvaraj, P -- Carpen, O -- Springer, T A -- Kuster, H -- Jouvin, M H -- Kinet, J P -- New York, N.Y. -- Science. 1989 Dec 22;246(4937):1608-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2531918" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/genetics ; Antigens, Differentiation/*genetics ; Cell Line ; Cell Membrane/immunology ; Flow Cytometry ; *Gene Expression Regulation ; Genes, Immunoglobulin ; Granulocytes/immunology ; Humans ; Immunoglobulin G ; Killer Cells, Natural/immunology ; L Cells (Cell Line)/immunology ; Mice ; Mutation ; RNA, Messenger/genetics/isolation & purification ; Receptors, Fc/*genetics ; Receptors, IgG ; Transcription, Genetic ; Transfection
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  • 51
    Publication Date: 1989-09-01
    Description: The expression of the late genes in bacteriophage T4 development is closely connected to viral DNA replication. Three T4-encoded DNA polymerase accessory proteins are shown to stimulate transcription at T4 late promoters in an adenosine triphosphate (ATP) hydrolysis-requiring process. The properties of the activation resemble those found for enhancers of eukaryotic transcription. However, the nature of the enhancer of T4 late transcription is novel in that it is a structure--a break in the nontranscribed DNA stand--to which the three replication proteins bind, rather than a sequence. Since the three DNA polymerase accessory proteins are carried on the moving replication fork as part of the replisome, we postulate that viral DNA replication forks act, in vivo, as the mobile enhancers of T4 late gene transcription. Whereas Escherichia coli RNA polymerase bearing the T4 gene 55 protein can selectively recognize T4 late promoters, it is only capable of responding to the transcription-enhancing activity of the three replication proteins on acquiring an additional T4-specific modification.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Herendeen, D R -- Kassavetis, G A -- Barry, J -- Alberts, B M -- Geiduschek, E P -- New York, N.Y. -- Science. 1989 Sep 1;245(4921):952-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Center for Molecular Genetics, 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/2672335" target="_blank"〉PubMed〈/a〉
    Keywords: *DNA Replication ; DNA, Viral/*genetics ; DNA-Directed DNA Polymerase/metabolism ; DNA-Directed RNA Polymerases/metabolism ; *Enhancer Elements, Genetic ; Escherichia coli/*genetics ; Gene Expression Regulation ; *Genes, Viral ; Plasmids ; Promoter Regions, Genetic ; T-Phages/*genetics ; *Transcription, Genetic
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  • 52
    Publication Date: 1989-01-27
    Description: Differential gene expression in the mother cell chamber of sporulating cells of Bacillus subtilis is determined in part by an RNA polymerase sigma factor called sigma K (or sigma 27). The sigma K factor was assigned as the product of the sporulation gene spoIVCB on the basis of the partial aminoterminal amino acid sequence of the purified protein. The spoIVCB gene is now shown to be a truncated gene capable of specifying only the amino terminal half of sigma K. The carboxyl terminal half is specified by another sporulation gene, spoIIIC, to which spoIVCB becomes joined inframe at an intermediate stage of sporulation by site-specific recombination within a 5-base pair repeated sequence. Juxtaposition of spoIVCB and spoIIIC need not be reversible in that the mother cell and its chromosome are discarded at the end of the developmental cycle. The rearrangement of chromosomal DNA could account for the presence of sigma K selectively in the mother cell and may be a precedent for the generation of cell type-specific regulatory proteins in other developmental systems where cells undergo terminal differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stragier, P -- Kunkel, B -- Kroos, L -- Losick, R -- New York, N.Y. -- Science. 1989 Jan 27;243(4890):507-12.〈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/2536191" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacillus subtilis/*genetics/physiology ; Base Sequence ; Cloning, Molecular ; DNA Probes ; DNA Restriction Enzymes ; DNA, Bacterial/genetics ; DNA-Directed RNA Polymerases/metabolism ; *Gene Expression Regulation ; *Gene Rearrangement ; *Genes, Bacterial ; Molecular Sequence Data ; Molecular Weight ; Mutation ; Nucleic Acid Hybridization ; Sigma Factor/genetics ; Spores, Bacterial ; Transcription Factors/*genetics
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  • 53
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-07-07
    Description: Protein interiors contain many tightly packed apolar atoms in a nearly crystalline state. Both shielding of apolar atoms from solvent and efficient interior packing arrangements affect protein stability, but their relative importance is unclear. To separate these effects, the stabilities of wild-type and mutant gene V proteins from bacteriophage fl were studied by measuring resistance to denaturation. The effects of subtle interior packing changes, both separate from and combined with changes in buried side chain hydrophobicity, were measured. For the interior apolar-to-apolar substitutions studied, the two effects were of the same magnitude and alteration of packing without accompanying hydrophobicity changes substantially destabilized the protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sandberg, W S -- Terwilliger, T C -- 5732 GM07281/GM/NIGMS NIH HHS/ -- GM38714/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Jul 7;245(4913):54-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2787053" target="_blank"〉PubMed〈/a〉
    Keywords: Calorimetry ; Coliphages/genetics ; Drug Stability ; Guanidine ; Guanidines ; Models, Molecular ; Mutation ; *Protein Conformation ; Protein Denaturation ; *Viral Proteins/genetics
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  • 54
    Publication Date: 1989-07-07
    Description: The insulin receptor has an intrinsic tyrosine kinase activity that is essential for signal transduction. A mutant insulin receptor gene lacking almost the entire kinase domain has been identified in an individual with type A insulin resistance and acanthosis nigricans. Insulin binding to the erythrocytes or cultured fibroblasts from this individual was normal. However receptor autophosphorylation and tyrosine kinase activity toward an exogenous substrate were reduced in partially purified insulin receptors from the proband's lymphocytes that had been transformed by Epstein-Barr virus. The insulin resistance associated with this mutated gene was inherited by the proband from her mother as an apparently autosomal dominant trait. Thus a deletion in one allele of the insulin receptor gene may be at least partly responsible for some instances of insulin-resistant diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taira, M -- Hashimoto, N -- Shimada, F -- Suzuki, Y -- Kanatsuka, A -- Nakamura, F -- Ebina, Y -- Tatibana, M -- Makino, H -- New York, N.Y. -- Science. 1989 Jul 7;245(4913):63-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Second Department of Internal Medicine, Chiba University School of Medicine, Inohana, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2544997" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Alleles ; Amino Acid Sequence ; Base Sequence ; *Chromosome Deletion ; Diabetes Mellitus, Type 1/enzymology/*genetics ; Female ; *Genes ; Humans ; Insulin Resistance ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Protein-Tyrosine Kinases/*genetics ; Receptor, Insulin/*genetics ; Restriction Mapping
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  • 55
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-05-19
    Description: During frog embryogenesis, mesoderm is specified in the equatorial region of the early embryo by a signal from the vegetal hemisphere. Prospective ectodermal cells dissected from the animal hemisphere can be respecified to form mesodermal tissues by recombination with vegetal tissue or by treatment with any of several polypeptide growth factors or growth factor-like molecules. Together with the discovery that several developmental mutations in Drosophila are in genes with significant homology to mammalian mitogens and oncogenes, these observations suggest that early developmental signals may use similar transduction pathways to mitogenic signals characterized in cultured mammalian cells. Whether mesoderm can be induced by activation of intracellular signal transduction pathways implicated in mitogenesis and oncogenesis has been investigated with the viral oncogene polyoma middle T. Microinjection of middle T messenger RNA into early embryos results in the respecification of isolated prospective ectodermal tissue to form characteristic mesodermal structures. Middle T in frog blastomeres appears to associate with cellular activities similar to those observed in polyoma-transformed mouse cells, and transformation-defective middle T mutants fail to induce mesoderm. These results suggest that early inductive signals and mitogenic and oncogenic stimuli may share common signal transduction pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitman, M -- Melton, D A -- New York, N.Y. -- Science. 1989 May 19;244(4906):803-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2658054" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Polyomavirus Transforming/genetics ; Blastocyst/physiology ; Blastomeres/physiology ; Ectoderm/physiology ; Immunosorbent Techniques ; Mesoderm/*physiology ; Mitosis ; Morphogenesis ; Muscles/embryology ; Mutation ; *Oncogenes ; Protein-Tyrosine Kinases/metabolism ; RNA, Messenger/genetics ; *Signal Transduction ; Transfection ; Transformation, Genetic ; Xenopus/*embryology
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  • 56
    Publication Date: 1989-03-03
    Description: Sindbis virus, an enveloped virus with a single-stranded RNA genome, was engineered to express a bacterial protein, chloramphenicol acetyltransferase (CAT), in cultured insect, avian, and mammalian cells. The vectors were self-replicating and gene expression was efficient and rapid; up to 10(8) CAT polypeptides were produced per infected cell in 16 to 20 hours. CAT expression could be made temperature-sensitive by means of a derivative that incorporated a temperature-sensitive mutation in viral RNA synthesis. Vector genomic RNAs were packaged into infectious particles when Sindbis helper virus was used to supply virion structural proteins. The vector RNAs were stable to at least seven cycles of infection. The expression of CAT increased about 10(3)-fold, despite a 10(15)-fold dilution during the passaging. Sindbis virus vectors should prove useful for expressing large quantities of gene products in a variety of animal cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xiong, C -- Levis, R -- Shen, P -- Schlesinger, S -- Rice, C M -- Huang, H V -- AG05681/AG/NIA NIH HHS/ -- AI11377/AI/NIAID NIH HHS/ -- AI24134/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 3;243(4895):1188-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, 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/2922607" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes ; Animals ; Bacteria/enzymology ; Cells, Cultured ; Chick Embryo ; Chloramphenicol O-Acetyltransferase/*genetics ; Codon ; Cricetinae ; DNA/genetics ; Drosophila ; Gene Amplification ; Gene Expression Regulation ; *Genetic Engineering ; *Genetic Vectors ; Humans ; Quail ; RNA, Viral/*genetics ; Sindbis Virus/*genetics ; Transcription, Genetic ; Transfection
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  • 57
    Publication Date: 1989-08-18
    Description: The chemical identity of the amino acid free-radical site that represents one of the two oxidizing equivalents stored in the H2O2-oxidized intermediate (compound ES) of the mitochondrial heme enzyme, cytochrome c peroxidase (CcP) has been sought for almost a quarter of a century. Site-directed mutagenesis alone cannot yield this answer. Low-temperature 35-gigahertz (Q-band) electron nuclear double resonance (ENDOR) spectroscopy was used to examine compound ES prepared from proteins containing specifically deuterated methionine or tryptophan, as well as the amino acid replacement Trp51----Phe. The results definitely identify the site of the radical in compound ES as tryptophan, most likely Trp191.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sivaraja, M -- Goodin, D B -- Smith, M -- Hoffman, B M -- GM-33804/GM/NIGMS NIH HHS/ -- GM-41049/GM/NIGMS NIH HHS/ -- HL-13531/HL/NHLBI NIH HHS/ -- R01 GM041049/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):738-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Northwestern University, Evanston, IL 60208.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2549632" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; *Cytochrome-c Peroxidase/genetics ; Electron Spin Resonance Spectroscopy ; Escherichia coli/enzymology ; Free Radicals ; Mutation ; Oxidation-Reduction ; *Peroxidases/genetics ; Recombinant Proteins ; *Tryptophan
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  • 58
    Publication Date: 1989-05-12
    Description: Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Slamon, D J -- Godolphin, W -- Jones, L A -- Holt, J A -- Wong, S G -- Keith, D E -- Levin, W J -- Stuart, S G -- Udove, J -- Ullrich, A -- CA 36827/CA/NCI NIH HHS/ -- CA 48780/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1989 May 12;244(4905):707-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, U.C.L.A. School of Medicine 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2470152" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers, Tumor ; Breast Neoplasms/*genetics ; Cloning, Molecular ; DNA/analysis ; Female ; Gene Amplification ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Nucleic Acid Hybridization ; Ovarian Neoplasms/*genetics ; Prognosis ; Protein Kinases ; Proto-Oncogene Proteins/*genetics ; *Proto-Oncogenes ; RNA/analysis ; Receptor, ErbB-2
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  • 59
    Publication Date: 1989-03-31
    Description: The discovery that the AP-1 family of enhancer binding factors includes a complex of the cellular Fos (cFos) and cellular Jun (cJun) proteins established a direct and important link between oncogenesis and transcriptional regulation. Homodimeric cJun protein synthesized in vitro is capable of binding selectively to AP-1 recognition sites, whereas the cFos polypeptide is not. When cotranslated, the cFos and cJun proteins can form a stable, heterodimeric complex with the DNA binding properties of AP-1/cJun. The related proteins Jun B and vJun are also able to form DNA binding complexes with cFos. Directed mutagenesis of the cFos protein reveals that a leucine repeat structure is required for binding to cJun, in a manner consistent with the proposed function of the "leucine zipper." A novel domain adjacent to, but distinct from, the leucine repeat of cFos is required for DNA binding by cFos-cJun heterodimers. Thus experimental evidence is presented that leucine repeats can mediate complex formation between heterologous proteins and that promotes further understanding of the molecular mechanisms underlying the function of two proto-oncogene products.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Turner, R -- Tjian, R -- New York, N.Y. -- Science. 1989 Mar 31;243(4899):1689-94.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2494701" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Chromatography, Affinity ; DNA/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation ; Humans ; *Leucine ; Macromolecular Substances ; Molecular Sequence Data ; Mutation ; Oncogenes ; Protein Biosynthesis ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; Rats ; Repetitive Sequences, Nucleic Acid ; Structure-Activity Relationship ; Transcription Factors/genetics/*metabolism
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  • 60
    Publication Date: 1989-07-28
    Description: Amyloid deposition in senile plaques and the cerebral vasculature is a marker of Alzheimer's disease. Whether amyloid itself contributes to the neurodegenerative process or is simply a by-product of that process is unknown. Pheochromocytoma (PC12) and fibroblast (NIH 3T3) cell lines were transfected with portions of the gene for the human amyloid precursor protein. Stable PC12 cell transfectants expressing a specific amyloid-containing fragment of the precursor protein gradually degenerated when induced to differentiate into neuronal cells with nerve growth factor. Conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against the amyloid polypeptide. Thus, a peptide derived from the amyloid precursor may be neurotoxic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yankner, B A -- Dawes, L R -- Fisher, S -- Villa-Komaroff, L -- Oster-Granite, M L -- Neve, R L -- HD 18655/HD/NICHD NIH HHS/ -- HD 18658/HD/NICHD NIH HHS/ -- NS 01240/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Jul 28;245(4916):417-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Harvard Medical School, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2474201" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*etiology/pathology ; Amyloid/genetics/*physiology ; Blotting, Northern ; Cell Line ; Fibroblasts ; Gene Expression Regulation ; Humans ; Immunoblotting ; Neurons/pathology ; Nucleic Acid Hybridization ; Pheochromocytoma ; Protein Precursors/genetics/*physiology ; RNA/analysis/genetics ; Restriction Mapping ; Transfection ; Tumor Cells, Cultured
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  • 61
    Publication Date: 1989-08-18
    Description: Oligonucleotides that bind to duplex DNA in a sequence-specific manner by triple helix formation offer an approach to the experimental manipulation of sequence-specific protein binding. Micromolar concentrations of pyrimidine oligodeoxyribonucleotides are shown to block recognition of double helical DNA by prokaryotic modifying enzymes and a eukaryotic transcription factor at a homopurine target site. Inhibition is sequence-specific. Oligonucleotides containing 5-methylcytosine provide substantially more efficient inhibition than oligonucleotides containing cytosine. The results have implications for gene-specific repression by oligonucleotides or their analogs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maher, L J 3rd -- Wold, B -- Dervan, P B -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):725-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2549631" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine ; Animals ; Base Sequence ; Cytosine/analogs & derivatives ; DNA/*metabolism ; DNA Restriction Enzymes ; DNA, Recombinant ; DNA-Binding Proteins/*antagonists & inhibitors/metabolism ; Deoxyribonucleases, Type II Site-Specific/metabolism ; Metallothionein/genetics ; Methylation ; Mice ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Oligodeoxyribonucleotides/*pharmacology ; Plasmids ; Promoter Regions, Genetic ; Structure-Activity Relationship ; Transcription Factors/metabolism
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-06-16
    Description: Recombinant DNA clones containing large pieces of DNA are useful in the study of large genetic units, but these are difficult to make in most bacterial cloning vectors. A strategy is described that uses general and site-specific recombination to construct large pieces of eukaryotic DNA from smaller cloned segments. The large clones are propagated on F factor-based plasmids in Escherichia coli. They can be easily modified to introduce mutations or rearrangements. These techniques were applied to the construction of large DNA segments from the bithorax complex of Drosophila.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Connor, M -- Peifer, M -- Bender, W -- New York, N.Y. -- Science. 1989 Jun 16;244(4910):1307-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2660262" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Recombinant/*biosynthesis ; DNA, Superhelical/biosynthesis ; Escherichia coli/*genetics ; *F Factor ; Genetic Vectors ; Mutation ; Plasmids ; *Transformation, Bacterial
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  • 63
    Publication Date: 1989-03-31
    Description: The protein products of the fos and jun proto-oncogenes form a heterodimeric complex that participates in a stable high affinity interaction with DNA elements containing AP-1 binding sites. The effects of deletions and point mutations in Fos and Jun on protein complex formation and DNA binding have been examined. The data suggest that Fos and Jun dimerize via a parallel interaction of helical domains containing a heptad repeat of leucine residues (the leucine zipper). Dimerization is required for DNA binding and results in the appropriate juxtaposition of basic amino acid regions from Fos and Jun, both of which are required for association with DNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gentz, R -- Rauscher, F J 3rd -- Abate, C -- Curran, T -- New York, N.Y. -- Science. 1989 Mar 31;243(4899):1695-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Oncology, Roche Institute of Molecular Biology, Nutley, NJ 07110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2494702" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Cross-Linking Reagents ; DNA/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Glutaral ; Immunosorbent Techniques ; *Leucine ; Macromolecular Substances ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; Rats ; Repetitive Sequences, Nucleic Acid ; Structure-Activity Relationship ; Transcription Factors/genetics/*metabolism
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-17
    Description: A true Bronsted analysis of proton transfer in an enzyme mechanism is made possible by the chemical rescue of an inactive mutant of aspartate aminotransferase, where the endogenous general base, Lys258, is replaced with Ala by site-directed mutagenesis. Catalytic activity is restored to this inactive mutant by exogenous amines. The eleven amines studied generate a Bronsted correlation with beta of 0.4 for the transamination of cysteine sulfinate, when steric effects are included in the regression analysis. Localized mutagenesis thus allows the classical Bronsted analysis of transition-state structure to be applied to enzyme-catalyzed reactions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toney, M D -- Kirsch, J F -- GM07232/GM/NIGMS NIH HHS/ -- GM35393/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 17;243(4897):1485-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2538921" target="_blank"〉PubMed〈/a〉
    Keywords: Amines ; Aspartate Aminotransferases/*metabolism ; Binding Sites ; Catalysis ; Escherichia coli/enzymology ; Kinetics ; Lysine ; Mutation ; Protons
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  • 65
    Publication Date: 1989-02-10
    Description: The T cell lymphokine, interleukin-2 (IL-2), plays a pivotal role in an immune response by stimulating antigen-activated B lymphocytes to progress through the cell cycle and to differentiate into antibody-secreting cells. An IL-2 inducible B lymphoma line, in which the growth and differentiation responses are uncoupled, provides a model system for dissecting the signaling mechanisms operating in each response. This system was used to show that both signals are initiated by IL-2 binding to a single, unifunctional receptor complex. Moreover, both signals are transduced by a pathway that does not involve any known second messenger system and that can be blocked by a second T cell lymphokine, interleukin 4. These findings suggest that the pleiotrophic effects of IL-2 are determined by different translations of the signal in the nucleus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tigges, M A -- Casey, L S -- Koshland, M E -- AI07079/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 10;243(4892):781-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chiron Corporation, Emeryville, CA 94608.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2492678" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antibody Formation ; B-Lymphocytes/*physiology ; Calcium/physiology ; Gene Expression Regulation ; Immunoglobulin J-Chains/genetics ; Interleukin-2/*physiology ; Interleukin-4 ; Interleukins/pharmacology ; Lymphocyte Activation ; Mice ; Protein Kinase C/physiology ; Receptors, Interleukin-2/*physiology ; Tumor Cells, Cultured
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-06-16
    Description: Filamentous fungi are important in medicine, industry, agriculture, and basic biological research. For example, some fungal species are pathogenic to humans, whereas others produce beta-lactam antibiotics (penicillin and cephalosporin). Industrial strains produce large amounts of enzymes, such as glucoamylase and proteases, and low molecular weight compounds, such as citric acid. The largest and most economically important group of plant pathogens are fungi. Several fungal species have biological properties and genetic systems that make them ideally suited for basic biological research. Recently developed techniques for genetic engineering of filamentous fungi make it possible to alter their detrimental and beneficial activities in novel ways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Timberlake, W E -- Marshall, M A -- New York, N.Y. -- Science. 1989 Jun 16;244(4910):1313-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, University of Georgia, Athens 30602.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2525275" target="_blank"〉PubMed〈/a〉
    Keywords: Aspergillus nidulans/*genetics ; Forecasting ; Gene Expression Regulation ; Genetic Engineering/*methods/trends ; Mutation ; Neurospora/*genetics ; Neurospora crassa/*genetics ; Transformation, Genetic
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-24
    Description: When platelet-derived growth factor (PDGF) binds to its receptor on a quiescent fibroblast or smooth muscle cell, it stimulates a remarkably diverse group of biochemical responses, including changes in ion fluxes, activation of several kinases, alterations in cell shape, increased transcription of a number of genes, and stimulation of enzymes that regulate phospholipid metabolism. These and other reactions culminate, hours later, in DNA replication and cell division. How does the receptor for PDGF recognize and bind its specific ligand and then transduce this signal across the cell membrane via a single membrane-spanning region? Which of the immediate cellular responses are directly involved in the biochemical pathways that lead to DNA synthesis? How does the PDGF receptor trigger a diverse group of responses? Recent studies of the PDGF receptor have provided insight into these issues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, L T -- HL-32898/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 24;243(4898):1564-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2538922" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Gene Expression Regulation ; Humans ; Membrane Proteins/physiology/ultrastructure ; Molecular Structure ; Platelet-Derived Growth Factor/*physiology ; Protein-Tyrosine Kinases/physiology ; Receptors, Cell Surface/*physiology/ultrastructure ; Receptors, Platelet-Derived Growth Factor
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  • 68
    Publication Date: 1989-04-28
    Description: The interleukin-2 receptor alpha (IL-2R alpha) chain gene contains a sequence similar to the immunoglobulin (Ig) kappa (kappa) enhancer NF-kappa B binding site. This site, which is bound by the nuclear protein, NF-kappa B, is critical for Ig kappa gene expression. The major T cell nuclear factor that binds to the IL-2R alpha site in vitro appears indistinguishable from NF-kappa B. NF-kappa B binds to IL-2R alpha and kappa sequences with similar affinities; however, only the kappa site potently activates transcription from heterologous promoters. Thus, high-affinity NF-kappa B binding in vitro cannot be equated with transcriptional activation in vivo. Mutation of the NF-kappa B binding site in the context of an IL-2 R alpha promoter construct markedly diminished promoter activity in human T cell lymphotropic virus type I (HTLV-I)-transformed MT-2 cells but not in phorbol myristate acetate-stimulated Jurkat T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cross, S L -- Halden, N F -- Lenardo, M J -- Leonard, W J -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):466-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2497520" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Binding Sites ; Cell Line, Transformed ; DNA-Binding Proteins/*metabolism ; *Enhancer Elements, Genetic ; *Gene Expression Regulation ; HIV-1/genetics ; HeLa Cells ; Human T-lymphotropic virus 1 ; Humans ; Immunoglobulin kappa-Chains/*genetics ; Mice ; Molecular Sequence Data ; Mutation ; NF-kappa B ; Promoter Regions, Genetic ; Receptors, Interleukin-2/*genetics ; T-Lymphocytes/metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Transcription Factors/*metabolism ; Transcription, Genetic
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  • 69
    Publication Date: 1989-05-12
    Description: Membrane fusion induced by the envelope glycoproteins of human and simian immunodeficiency viruses (HIV and SIVmac) is a necessary step for the infection of CD4 cells and for the formation of syncytia after infection. Identification of the region in these molecules that mediates the fusion events is important for understanding and possibly interfering with HIV/SIVmac infection and pathogenesis. Amino acid substitutions were made in the 15 NH2-terminal residues of the SIVmac gp32 transmembrane glycoprotein, and the mutants were expressed in recombinant vaccinia viruses, which were then used to infect CD4-expressing T cell lines. Mutations that increased the overall hydrophobicity of the gp32 NH2-terminus increased the ability of the viral envelope to induce syncytia formation, whereas introduction of polar or charged amino acids in the same region abolished the fusogenic function of the viral envelope. Hydrophobicity in the NH2-terminal region of gp32 may therefore be an important correlate of viral virulence in vivo and could perhaps be exploited to generate a more effective animal model for the study of acquired immunodeficiency syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bosch, M L -- Earl, P L -- Fargnoli, K -- Picciafuoco, S -- Giombini, F -- Wong-Staal, F -- Franchini, G -- New York, N.Y. -- Science. 1989 May 12;244(4905):694-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2541505" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Line ; Cloning, Molecular ; DNA, Viral/genetics ; *Gene Products, env ; HIV/*analysis ; HIV Antigens/metabolism ; HIV Envelope Protein gp120 ; HIV Envelope Protein gp41 ; Humans ; Membrane Glycoproteins ; Molecular Sequence Data ; Mutation ; *Retroviridae Proteins/genetics/metabolism/pharmacology ; *Retroviridae Proteins, Oncogenic ; Retroviruses, Simian/*analysis ; Structure-Activity Relationship ; T-Lymphocytes, Helper-Inducer/microbiology ; Transfection ; Vaccinia virus/genetics ; *Viral Envelope Proteins/genetics/metabolism/pharmacology ; *Viral Fusion Proteins
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-02-10
    Description: Pituitary-specific expression of the growth hormone (GH) gene is governed by a transcription factor, GHF-1, that binds to two sites within its promoter. Recently, GHF-1 was shown to be a member of the homeobox family of DNA-binding proteins. An important question is whether GHF-1 controls the expression of other pituitary specific genes, such as prolactin (Prl), expressed in closely related cell types. To this end, GHF-1 was purified from extracts of GH- and Prl-expressing pituitary tumor cells and identified as a 33-kilodalton polypeptide. Although GHF-1 bound to and activated the GH promoter, it did not recognize the Prl promoter. However, at least one other factor in the same extracts, which was easily separated from GHF-1, bound to several sites within the Prl but not the GH promoter. Antibodies to GHF-1 did not react with the Prl binding activity. These results imply that the pituitary-specific expression of GH and Prl is governed by two distinct trans-acting factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Castrillo, J L -- Bodner, M -- Karin, M -- DK-38527/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 10;243(4892):814-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, School of Medicine, 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/2563596" target="_blank"〉PubMed〈/a〉
    Keywords: DNA-Binding Proteins/*genetics ; Gene Expression Regulation ; *Genes, Homeobox ; Growth Hormone/*genetics ; Humans ; Molecular Weight ; Peptide Mapping ; Pituitary Gland/physiology ; Prolactin/genetics ; Promoter Regions, Genetic ; Transcription Factors/*genetics ; Tumor Cells, Cultured
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-02-24
    Description: The genetic control of neuronal differentiation has been studied by examining mutations that affect the development and function of the six touch receptor neurons of the nematode Caenorhabditis elegans. By screening for touch-insensitive mutants, it has been possible to identify 18 genes (represented by 417 mutations) that are required at various stages in the developmental program for touch cell differentiation. Two of the genes are needed for the generation of precursors in the touch cell lineages; without the precursors, touch cells are not made. A third gene, mec-3, specifies the differentiation of the touch cells, probably by acting as a transcription factor. The remaining 15 genes are likely targets of mec-3 action; mutants defective in these genes have nonfunctioning, yet differentiated, touch cells. Some of these latter genes are needed for the formation of cell-specific components of the touch cells, such as a set of microtubules that are only found in these cells. The study of the touch genes should help us understand how touch cell fate is determined, how microtubule form is specified, and, perhaps, how mechanical stimuli are transduced.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chalfie, M -- Au, M -- GM30997/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 24;243(4894 Pt 1):1027-33.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Columbia University, New York, NY 10027.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2646709" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis/cytology/*genetics/growth & development ; Cell Differentiation ; *Gene Expression Regulation ; Mechanoreceptors/cytology ; Mutation ; Neurons/*cytology ; Touch
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Culliton, B J -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):413.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2655080" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fraud/legislation & jurisprudence ; Gene Expression Regulation ; Genes, Immunoglobulin ; History, 20th Century ; Mice ; Mice, Transgenic ; Publishing/*standards ; Research/*standards ; Research Personnel ; United States
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-12-22
    Description: Expression of high levels of the structural proteins of the human immunodeficiency virus type 1 (HIV-1) requires the presence of the protein encoded by the rev open reading frame (Rev) and its associated target sequence CAR (cis anti-repression sequence) which is present in the env region of viral RNA. Extensive mutagenesis demonstrated that CAR has a complex secondary structure consisting of a central stem and five stem/loops. Disruption of any of these structures severely impaired the Rev response, but many of the stem/loops contain material that was unnecessary for Rev regulation and must be retained in these structures to avoid disturbing adjacent structures critical for CAR function. Probably no more than two of the described structural components are involved in sequence-specific recognition by regulatory proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dayton, E T -- Powell, D M -- Dayton, A I -- New York, N.Y. -- Science. 1989 Dec 22;246(4937):1625-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2688093" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Line ; Chromosome Deletion ; Gene Amplification ; Gene Products, rev/genetics/*metabolism ; *Genes, Viral ; HIV-1/*genetics ; Models, Structural ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Plasmids ; RNA, Viral/*genetics ; Software ; Trans-Activators/*metabolism ; Transfection ; Viral Envelope Proteins/genetics ; rev Gene Products, Human Immunodeficiency Virus
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  • 74
    Publication Date: 1989-05-12
    Description: The age of the molecular organization of life as expressed in the genetic code can be estimated from experimental data. Comparative sequence analysis of transfer RNA by the method of statistical geometry in sequence space suggests that about one-third of the present transfer RNA sequence divergence was present at the urkingdom level about the time when archaebacteria separated from eubacteria. It is concluded that the genetic code is not older than, but almost as old as our planet. While this result may not be unexpected, it was not clear until now that interpretable data exist that permit inferences about such early stages of life as the establishment of the genetic code.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eigen, M -- Lindemann, B F -- Tietze, M -- Winkler-Oswatitsch, R -- Dress, A -- von Haeseler, A -- New York, N.Y. -- Science. 1989 May 12;244(4905):673-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institut fur biophysikalische Chemie, Gottingen, Federal Republic of Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2497522" target="_blank"〉PubMed〈/a〉
    Keywords: Anticodon ; Archaea/genetics ; Base Sequence ; *Biological Evolution ; Codon ; Computer Simulation ; Eubacterium/genetics ; *Genetic Code ; Mutation ; Nucleic Acid Conformation ; Phylogeny ; *RNA, Transfer ; Statistics as Topic ; Time Factors
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  • 75
    Publication Date: 1989-02-24
    Description: Facultative intracellular pathogens pose an important health problem because they circumvent a primary defense mechanism of the host: killing and degradation by professional phagocytic cells. A gene of the intracellular pathogen Salmonella typhimurium that is required for virulence and intracellular survival was identified and shown to have a role in resistance to defensins and possibly to other microbicidal mechanisms of the phagocyte. This gene may prove to be a regulatory element in the expression of virulence functions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fields, P I -- Groisman, E A -- Heffron, F -- AI07235/AI/NIAID NIH HHS/ -- AI22933/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1989 Feb 24;243(4894 Pt 1):1059-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2646710" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Proteins/*physiology ; Cytoplasmic Granules/analysis ; DNA, Bacterial/genetics ; Defensins ; *Genes, Bacterial ; Humans ; Macrophages/analysis/physiology ; Mice ; Mice, Inbred BALB C ; Mutation ; Neutrophils/analysis ; Nucleic Acid Hybridization ; Phagocytes/*physiology ; Plasmids ; Rabbits ; Salmonella typhimurium/*genetics/pathogenicity
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  • 76
    Publication Date: 1989-03-03
    Description: Gap junctions in the early amphibian embryo may play a fundamental role in the regulation of differentiation by mediating the cell-to-cell transfer of chemical signals. A complementary DNA encoding a gap junction present in Xenopus oocytes and early embryos has now been cloned and sequenced. This protein sequence is homologous to the well-characterized gap junction structural proteins rat connexin32 and connexin43. RNA blot analysis of total Xenopus oocyte RNA showed hybridization to a single 1.6-kilobase band. This messenger RNA is abundant in oocytes, decreases to levels below the sensitivity of our assay by stage 15 (18 hours), and is not detectable in RNA from a number of adult organs. To confirm that the oocyte cDNA encodes a gap junction channel, the protein was over expressed in Xenopus oocytes by injection of RNA synthesized in vitro. Pairs of RNA-injected oocytes formed many more time- and voltage-sensitive cell-cell channels than water-injected pairs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ebihara, L -- Beyer, E C -- Swenson, K I -- Paul, D L -- Goodenough, D A -- GM18974/GM/NIGMS NIH HHS/ -- GM37751/GM/NIGMS NIH HHS/ -- HL28958-06/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 3;243(4895):1194-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Columbia University, New York, NY 10032.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2466337" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cell Communication ; *Cloning, Molecular ; Connexins ; DNA Probes ; Electric Conductivity ; Female ; Gene Expression Regulation ; Intercellular Junctions/physiology ; Membrane Proteins/*genetics/physiology ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Oocytes/analysis/physiology ; RNA/analysis ; RNA, Messenger/analysis ; Rats ; Tissue Distribution ; Xenopus/*embryology
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  • 77
    Publication Date: 1989-12-22
    Description: One action of cyclosporin A thought to be central to many of its immunosuppressive effects is its ability to inhibit the early events of T lymphocyte activation such as lymphokine gene transcription in response to signals initiated at the antigen receptor. Cyclosporin A was found to specifically inhibit the appearance of DNA binding activity of NF-AT, AP-3, and to a lesser extent NF-kappa B, nuclear proteins that appear to be important in the transcriptional activation of the genes for interleukin-2 and its receptor, as well as several other lymphokines. In addition, cyclosporin A abolished the ability of the NF-AT binding site to activate a linked promoter in transfected mitogen-stimulated T lymphocytes and in lymphocytes from transgenic mice. These results indicate that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Emmel, E A -- Verweij, C L -- Durand, D B -- Higgins, K M -- Lacy, E -- Crabtree, G R -- CA 39612/CA/NCI NIH HHS/ -- HL 33942/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Dec 22;246(4937):1617-20.〈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/2595372" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Cell Line ; Chromosome Deletion ; Cyclosporins/*pharmacology ; Enhancer Elements, Genetic ; Gene Expression Regulation/*drug effects ; Genes/drug effects ; Humans ; Interleukin-2/genetics ; Lymphocyte Activation/*drug effects ; Molecular Sequence Data ; Mutation ; Nuclear Proteins/*antagonists & inhibitors ; Oligonucleotide Probes ; Receptors, Interleukin-2/genetics ; Repetitive Sequences, Nucleic Acid ; T-Lymphocytes/drug effects/*immunology ; Transcription, Genetic
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  • 78
    Publication Date: 1989-03-10
    Description: The antibiotic resistance gene neomycin phosphotransferase (neo) has been precisely targeted to a chromosomal region close to the cystic fibrosis (CF) locus on chromosome 7. The chromosomal target was the expressed SV40 array integrated at chromosome 7, band q31-q35 in a human-mouse hybrid cell line that contains chromosome 7 as the only human component. Stringent selection for neo expression by homologous recombination (3 of 11 correctly targeted) was achieved by fusing the SV40 large T antigen gene, in frame, to neo in a promoterless construct, such that G418 resistance depended on endogenous promoter function and read-through transcription. Chromosome-mediated gene transfer (CMGT) with G418 selection was then used generate mouse hybrids that carried the targeted locus intact, but retained only a fragment of human chromosome 7. This gene targeting strategy will access new regions of the human (or other mammalian) genome, create precise mutations efficiently by gene disruption, and potentially restore normal gene function by mutation correction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dorin, J R -- Inglis, J D -- Porteous, D J -- New York, N.Y. -- Science. 1989 Mar 10;243(4896):1357-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2538001" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Polyomavirus Transforming/genetics ; Cell Line ; Chromosome Mapping ; *Chromosomes, Human, Pair 7 ; Cloning, Molecular ; *Genes ; Genes, Viral ; Humans ; Hybrid Cells ; Kanamycin Kinase ; Mice ; Mutation ; Phosphotransferases/*genetics ; *Recombination, Genetic ; Restriction Mapping ; Simian virus 40/genetics ; *Transfection
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  • 79
    Publication Date: 1989-10-27
    Description: The prohormone-processing endoprotease (KEX2 gene product) of the yeast Saccharomyces cerevisiae is a membrane-bound, 135,000-dalton glycoprotein, which contains both asparagine-linked and serine- and threonine-linked oligosaccharide and resides in a secretory compartment. Analysis of mutant kex2 genes truncated at their 3' end indicates that carboxyl terminal domains of the enzyme are required for its proper localization within the cell. A human gene product, "furin," shares 50% identity with the catalytic domain of Kex2 protease and is, therefore, a candidate for a human prohormone-processing enzyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fuller, R S -- Brake, A J -- Thorner, J -- GM21841/GM/NIGMS NIH HHS/ -- RR01685/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1989 Oct 27;246(4929):482-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of California, Berkeley 94720.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2683070" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Humans ; Molecular Sequence Data ; Mutation ; *Proprotein Convertases ; Saccharomyces cerevisiae/enzymology ; *Saccharomyces cerevisiae Proteins ; Sequence Homology, Nucleic Acid ; Serine Endopeptidases/*genetics/metabolism ; Subcellular Fractions/enzymology ; *Subtilisins
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-08-18
    Description: Nerve growth factor (NGF) produced by telencephalic neurons provides critical trophic support for cholinergic neurons of the basal forebrain. In situ hybridization and nuclease protection analyses demonstrate that limbic seizures dramatically increase the amount of messenger RNA for NGF in the neurons of the hippocampal dentate gyrus within 1 hour of seizure onset and in broadly distributed neocortical and olfactory forebrain neurons some hours later. The increased messenger RNA species is indistinguishable from messenger RNA for transcript B of the beta subunit of NGF from mouse submandibular gland. Thus, the expression of a known growth factor is affected by unusual physiological activity, suggesting one route through which trophic interactions between neurons in adult brain can be modified.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gall, C M -- Isackson, P J -- NS00915/NS/NINDS NIH HHS/ -- NS24747/NS/NINDS NIH HHS/ -- NS26748/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1989 Aug 18;245(4919):758-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Neurobiology, University of California, Irvine 92717.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2549634" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autoradiography ; Endonucleases ; Gene Expression Regulation ; Guinea Pigs ; Hippocampus/physiopathology ; Limbic System/*physiopathology ; Mice ; Nerve Growth Factors/*genetics ; Neurons/*metabolism ; Nucleic Acid Hybridization ; RNA Probes ; RNA, Messenger/*biosynthesis ; Rats ; Seizures/*metabolism ; Single-Strand Specific DNA and RNA Endonucleases ; Telencephalon/metabolism ; Tissue Distribution
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  • 81
    Publication Date: 1989-07-14
    Description: Exposure of peripheral blood mononuclear cells (PBMC) to an 18-base c-myb antisense oligomer before mitogen or antigen stimulation resulted in almost complete inhibition of c-myb messenger RNA and protein synthesis and blockade of T lymphocyte proliferation. Expression of early and late activation markers, interleukin-2 receptor and transferrin receptor, respectively, by PBMC was unaffected by antisense oligomer exposure as was the expression of c-myc messenger RNA. In contrast, histone H3 messenger RNA levels and DNA content were selectively decreased. These results suggest that c-myb protein deprivation does not perturb T lymphocyte activation or early molecular events that may prepare the cell for subsequent proliferation. Rather, it appears to specifically block cells in late G1 or early S phase of the cell cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gewirtz, A M -- Anfossi, G -- Venturelli, D -- Valpreda, S -- Sims, R -- Calabretta, B -- CA01324/CA/NCI NIH HHS/ -- CA36896/CA/NCI NIH HHS/ -- CA46782/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1989 Jul 14;245(4914):180-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2665077" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Division/drug effects ; DNA/biosynthesis ; Fluorescent Antibody Technique ; Gene Expression Regulation ; Humans ; Image Processing, Computer-Assisted ; *Interphase ; *Lymphocyte Activation/drug effects ; Oligonucleotides/pharmacology ; Oligonucleotides, Antisense ; Proto-Oncogene Proteins/biosynthesis/*genetics/physiology ; Proto-Oncogene Proteins c-myb ; Proto-Oncogenes ; RNA, Messenger/biosynthesis/*genetics ; Receptors, Interleukin-2/biosynthesis ; Receptors, Transferrin/biosynthesis ; T-Lymphocytes/*cytology/metabolism
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  • 82
    Publication Date: 1989-03-03
    Description: Focal adhesion of leukocytes to the blood vessel lining is a key step in inflammation and certain vascular disease processes. Endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell surface glycoprotein expressed by cytokine-activated endothelium, mediates the adhesion of blood neutrophils. A full-length complementary DNA (cDNA) for ELAM-1 has now been isolated by transient expression in COS cells. Cells transfected with the ELAM-1 clone express a surface structure recognized by two ELAM-1 specific monoclonal antibodies (H4/18 and H18/7) and support the adhesion of isolated human neutrophils and the promyelocytic cell line HL-60. Expression of ELAM-1 transcripts in cultured human endothelial cells is induced by cytokines, reaching a maximum at 2 to 4 hours and decaying by 24 hours; cell surface expression of ELAM-1 protein parallels that of the mRNA. The primary sequence of ELAM-1 predicts an amino-terminal lectin-like domain, an EGF domain, and six tandem repetitive motifs (about 60 amino acids each) related to those found in complement regulatory proteins. A similar domain structure is also found in the MEL-14 lymphocyte cell surface homing receptor, and in granule-membrane protein 140, a membrane glycoprotein of platelet and endothelial secretory granules that can be rapidly mobilized (less than 5 minutes) to the cell surface by thrombin and other stimuli. Thus, ELAM-1 may be a member of a nascent gene family of cell surface molecules involved in the regulation of inflammatory and immunological events at the interface of vessel wall and blood.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bevilacqua, M P -- Stengelin, S -- Gimbrone, M A Jr -- Seed, B -- P01 HL-36028/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 3;243(4895):1160-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, 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/2466335" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Adhesion ; DNA/genetics ; E-Selectin ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; Humans ; Immunoassay ; Interleukin-1/pharmacology ; *Membrane Glycoproteins ; Molecular Sequence Data ; Neutrophils/*physiology ; Nucleic Acid Hybridization ; Recombinant Proteins ; Sequence Homology, Nucleic Acid ; Transcription, Genetic ; Transfection ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/pharmacology
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  • 83
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-09-29
    Description: Transformation by the v-sis oncogene appears to require an interaction of its protein product, p28v-sis, with the receptor for the platelet-derived growth factor (PDGF). However, this interaction may not occur at the cell surface as predicted by the autocrine hypothesis because phenotypic transformation was not reversed by incubation of SSV-NRK cells with antisera to PDGF and because morphological transformation did not occur when nontransformed NRK cells were cultured continuously with p28v-sis. A mutant of the wild-type v-sis gene was constructed that encodes a v-sis protein targeted for retention within the endoplasmic reticulum and Golgi. NRK cells expressing the mutant v-sis gene did not secrete any detectable v-sis protein but were as fully transformed as wild-type v-sis transfectants. The results support a mechanism of transformation by v-sis in which internal activation of the PDGF receptor occurs before expression of either p28v-sis or the PDGF receptor at the cell surface.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bejcek, B E -- Li, D Y -- Deuel, T F -- CA49712/CA/NCI NIH HHS/ -- HL14147/HL/NHLBI NIH HHS/ -- HL31102/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1989 Sep 29;245(4925):1496-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2551043" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Cell Line, Transformed ; Molecular Sequence Data ; Mutation ; Oncogene Proteins v-sis ; Platelet-Derived Growth Factor/*biosynthesis ; Receptors, Cell Surface ; Receptors, Platelet-Derived Growth Factor ; Retroviridae Proteins/genetics/*physiology ; Sarcoma Virus, Woolly Monkey ; *Transformation, Genetic
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-02-17
    Description: Specification of cell fate in the compound eye of Drosophila appears to be controlled entirely by cell interactions. The sevenless gene is required for the correct determination of one of the eight photoreceptor cells (R7) in each ommatidium. It encodes a transmembrane protein with a tyrosine kinase domain and is expressed transiently on a subpopulation of ommatidial precursor cells including the R7 precursors. It is shown here that heat shock-induced indiscriminate expression of a sevenless complementary DNA throughout development can correctly specify R7 cell identity without affecting the development of other cells. Furthermore, discontinuous supply of sevenless protein during eye development leads to the formation of mosaic eyes containing stripes of sevenless+ and sevenless- ommatidia, suggesting that R7 cell fate can be specified only within a relatively short period during ommatidial assembly. These results support the hypothesis that the specification of cell fate by position depends on the interaction of a localized signal with a receptor present on many undifferentiated cells, and that the mere presence of the receptor alone is not sufficient to specify cell fate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Basler, K -- Hafen, E -- New York, N.Y. -- Science. 1989 Feb 17;243(4893):931-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Zoologisches Institut, Universitat Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2493159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Communication ; Drosophila melanogaster/anatomy & histology/*genetics ; Eye/anatomy & histology/metabolism ; *Genes ; Heat-Shock Proteins/genetics ; Mutation ; Promoter Regions, Genetic ; Protein-Tyrosine Kinases/genetics ; RNA, Messenger/genetics
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  • 85
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-06-16
    Description: Homologous recombination between DNA sequences residing in the chromosome and newly introduced, cloned DNA sequences (gene targeting) allows the transfer of any modification of the cloned gene into the genome of a living cell. This article discusses the current status of gene targeting with particular emphasis on germ line modification of the mouse genome, and describes the different methods so far employed to identify those rare embryonic stem cells in which the desired targeting event has occurred.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Capecchi, M R -- New York, N.Y. -- Science. 1989 Jun 16;244(4910):1288-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, 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/2660260" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chimera ; Forecasting ; Hypoxanthine Phosphoribosyltransferase/*genetics ; Mutation ; *Recombination, Genetic ; Stem Cells/*physiology
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  • 86
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-03
    Description: Decay accelerating factor (DAF) is anchored to the plasma membrane by a glycophospholipid (GPI) membrane anchor covalently attached to the COOH-terminus of the protein. A hydrophobic domain located at the COOH-terminus is required for anchor attachment; DAF molecules lacking this domain are secreted. Replacement of the COOH-terminal hydrophobic domain with a signal peptide that normally functions in membrane translocation, or with a random hydrophobic sequence, results in efficient and correct processing, producing GPI-anchored DAF on the cell surface. The structural requirements for GPI anchor attachment and for membrane translocation are therefore similar, presumably depending on overall hydrophobicity rather than specific sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Caras, I W -- Weddell, G N -- New York, N.Y. -- Science. 1989 Mar 3;243(4895):1196-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genentech, South San Francisco, CA 94080.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2466338" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Antigens, CD55 ; Blood Proteins ; *Carbohydrate Metabolism ; Cell Line ; Cell Membrane/*metabolism ; Complement Inactivator Proteins ; Ethanolamine ; Ethanolamines/metabolism ; Growth Hormone ; Humans ; Immunosorbent Techniques ; Membrane Proteins/genetics/*metabolism/secretion ; Mutation ; Phosphatidylinositol Diacylglycerol-Lyase ; Phosphatidylinositols/metabolism ; Phospholipids/*metabolism ; Phosphoric Diester Hydrolases/metabolism ; Protein Sorting Signals/*physiology ; Structure-Activity Relationship ; Transfection
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-01-20
    Description: Interaction of antigen in the proper histocompatibility context with the T lymphocyte antigen receptor leads to an orderly series of events resulting in morphologic change, proliferation, and the acquisition of immunologic function. In most T lymphocytes two signals are required to initiate this process, one supplied by the antigen receptor and the other by accessory cells or agents that activate protein kinase C. Recently, DNA sequences have been identified that act as response elements for one or the other of the two signals, but do not respond to both signals. The fact that these sequences lie within the control regions of the same genes suggests that signals originating from separate cell membrane receptors are integrated at the level of the responsive gene. The view is put forth that these signals initiate a contingent series of gene activations that bring about proliferation and impart immunologic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crabtree, G R -- CA 39612/CA/NCI NIH HHS/ -- HL 33942/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Jan 20;243(4889):355-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Stanford University Medical School, CA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2783497" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Expression Regulation ; Humans ; Interleukin-2/genetics ; *Lymphocyte Activation ; Mice ; Oncogenes ; Protein-Tyrosine Kinases/genetics ; T-Lymphocytes/*physiology ; Time Factors
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  • 88
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-03-03
    Description: The molecules with which the platelet-derived growth factor (PDGF) receptor interacts to elicit the biochemical reactions responsible for cell proliferation have not been identified. Antisera directed against specific PDGF receptor peptides coprecipitated a phosphatidylinositol (PI) kinase and the PDGF receptor. Immunoprecipitates from PDGF-stimulated cells contained 10 to 50 times as much PI kinase as those from unstimulated cells. Mutation of the PDGF receptor by deletion of its kinase insert region resulted in a receptor markedly less effective than the wild type in eliciting cell proliferation and defective in PDGF-stimulated PI kinase, but still capable of PDGF-induced receptor autophosphorylation and phosphoinositide hydrolysis. These data show that the PDGF receptor is physically associated with a PDGF-sensitive PI kinase that is distinct from tyrosine kinase and is not required for PDGF-induced PI hydrolysis. The finding that the mutant PDGF receptor missing the kinase insert domain elicited known early biochemical responses to PDGF, but did not associate with or regulate PI kinase, suggests a novel role for the receptor-associated PI kinase in the transmission of mitogenic signals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Coughlin, S R -- Escobedo, J A -- Williams, L T -- HL 32898/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1989 Mar 3;243(4895):1191-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2466336" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Phosphatidylinositol 4-Kinase ; Animals ; Cell Line ; Chromatography ; Cricetinae ; Immunoassay ; Immunosorbent Techniques ; Mice ; Mice, Inbred BALB C ; Mutation ; Phosphatidylinositols/metabolism ; Phosphorylation ; Phosphotransferases/*metabolism ; Phosphotyrosine ; Platelet-Derived Growth Factor/pharmacology ; Protein-Tyrosine Kinases/metabolism ; Receptors, Cell Surface/genetics/*metabolism ; Receptors, Platelet-Derived Growth Factor ; *Signal Transduction ; Tyrosine/analogs & derivatives/metabolism
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1989-04-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Culliton, B J -- New York, N.Y. -- Science. 1989 Apr 28;244(4903):412-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2655079" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biomedical Research ; Federal Government ; Fraud/legislation & jurisprudence ; Gene Expression Regulation ; Genes, Immunoglobulin ; History, 20th Century ; Mice ; Mice, Transgenic ; Publishing/*standards ; Research/*standards ; Research Personnel ; United States
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  • 90
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1988-11-25
    Description: The human immunodeficiency virus type 1 (HIV-1) shows extensive genetic variation and undergoes rapid evolution. The fidelity of purified HIV-1 reverse transcriptase was measured during DNA polymerization in vitro by means of three different assays. Reverse transcriptase from HIV-1 introduced base-substitution errors in DNA from the bacteriophage phi X174 amber3 at estimated frequencies of 1/2000 to 1/4000. Analyses of misincorporation rates opposite a single template adenine residue showed that HIV-1 reverse transcriptase catalyzed nucleotide mismatches with a specificity of A:C much greater than A:G greater than A:A. The high error rate of HIV-1 reverse transcriptase in vitro translates to approximately five to ten errors per HIV-1 genome per round of replication in vivo. This high error rate suggests that misincorporation by HIV-1 reverse transcriptase is, at least in part, responsible for the hypermutability of the AIDS virus. The specificity of misincorporation may provide a basis for the systematic construction of antiviral nucleosides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Preston, B D -- Poiesz, B J -- Loeb, L A -- CA-07263-03/CA/NCI NIH HHS/ -- N01AI72654/AI/NIAID NIH HHS/ -- R35-CA-39903/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1988 Nov 25;242(4882):1168-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Washington, Seattle 98195.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2460924" target="_blank"〉PubMed〈/a〉
    Keywords: Avian Myeloblastosis Virus/enzymology ; Bacteriophage phi X 174/genetics ; DNA/*biosynthesis ; DNA Polymerase II/metabolism ; DNA, Viral/biosynthesis ; Electrophoresis, Polyacrylamide Gel ; HIV/*enzymology/genetics ; Kinetics ; Moloney murine leukemia virus/enzymology ; Mutation ; Nucleotides/metabolism ; RNA-Directed DNA Polymerase/*metabolism
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  • 91
    Publication Date: 1988-07-01
    Description: Expression of the interleukin-2 receptor (IL-2R alpha) gene is activated by the transcriptional activator protein, Tax (previously referred to as the tat gene product), encoded by the human T-cell leukemia virus (HTLV-I). Multiple protein binding sites for specific DNA-protein interactions were identified over the upstream IL-2R alpha transcriptional regulatory sequences. However, only one region, which includes the sequence motif GGGGAATCTCCC, was required for activation by both the tax gene product and mitogenic stimulation. Remarkably, this sequence also bound the nuclear factor NF kappa B, which is important for induction of kappa-immunoglobulin gene expression. A model is presented whereby regulation of cellular gene expression by the HTLV-I tax gene product occurs via an indirect mechanism that may involve a post-translational modification of preexistent cellular transcription factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruben, S -- Poteat, H -- Tan, T H -- Kawakami, K -- Roeder, R -- Haseltine, W -- Rosen, C A -- New York, N.Y. -- Science. 1988 Jul 1;241(4861):89-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Oncology, Roche Institute of Molecular Biology, Nutley, NJ 07110.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2838905" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Binding Sites ; Cell Line ; DNA/genetics/metabolism ; Deltaretrovirus/*genetics ; Gene Expression Regulation/*drug effects ; Gene Products, tat ; Immunoglobulin kappa-Chains/genetics ; Mutation ; Plasmids ; Promoter Regions, Genetic ; Receptors, Immunologic/*genetics ; Receptors, Interleukin-2 ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/genetics/metabolism/*pharmacology
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1988-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schekman, R -- Payne, G -- New York, N.Y. -- Science. 1988 Feb 19;239(4842):919.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3277285" target="_blank"〉PubMed〈/a〉
    Keywords: Clathrin/genetics/*physiology ; Mutation ; Saccharomyces cerevisiae/genetics/*physiology
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  • 93
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1988-08-19
    Description: In mammalian cells, the glucocorticoid receptor binds specifically to glucocorticoid response element (GRE) DNA sequences and enhances transcription from linked promoters. It is shown here that derivatives of the glucocorticoid receptor also enhance transcription when expressed in yeast. Receptor-mediated enhancement in yeast was observed in fusions of GRE sequences to the yeast cytochrome c1 (CYC1) promoter; the CYC1 upstream activator sequences were not essential, since enhancement was observed in fusions of GREs to mutant CYC1 promoters retaining only the TATA region and transcription startpoints. It is concluded that the receptor operates by a common, highly conserved mechanism in yeast and mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schena, M -- Yamamoto, K R -- CA20535-12/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1988 Aug 19;241(4868):965-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco 94143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3043665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA/metabolism ; *Enhancer Elements, Genetic ; Gene Expression Regulation ; Immunoassay ; Plasmids ; Promoter Regions, Genetic ; Rats ; Receptors, Glucocorticoid/*genetics ; Saccharomyces cerevisiae/*genetics ; *Transcription, Genetic
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1988-04-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schleif, R -- New York, N.Y. -- Science. 1988 Apr 8;240(4849):127-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3353710" target="_blank"〉PubMed〈/a〉
    Keywords: DNA/*genetics ; DNA-Binding Proteins/physiology ; Eukaryotic Cells/physiology ; Gene Expression Regulation ; Nucleic Acid Conformation ; Prokaryotic Cells/physiology ; Regulatory Sequences, Nucleic Acid
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  • 95
    Publication Date: 1988-07-29
    Description: An octamer DNA sequence plays a critical role in directing transcription of immunoglobulin genes in B lymphocytes. A new technique of direct binding of radioactive DNA was used to screen a complementary DNA expression library from the BJAB cell line in lambda gt11 phage to derive molecular cDNA clones representing a putative B lymphocyte-specific octamer binding protein. The plaques were screened with DNA containing four copies of the octamer sequence and positive phage recombinants were identified. The fusion protein produced on inducing a lysogen of one phage bound to a monomeric octamer probe. The cDNA insert from this phage hybridized to messenger RNA found in B lymphocytes, but not in most other cells. Thus, this cDNA derives from a gene (oct-2) that specifies an octamer binding protein expressed preferentially in B lymphocytes, proving that, for at least one gene, a cell-specific transcription factor exists and its amount is controlled through messenger RNA availability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Staudt, L M -- Clerc, R G -- Singh, H -- LeBowitz, J H -- Sharp, P A -- Baltimore, D -- P01-CA42063/CA/NCI NIH HHS/ -- P30-CAL4051/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1988 Jul 29;241(4865):577-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3399892" target="_blank"〉PubMed〈/a〉
    Keywords: Cloning, Molecular ; DNA/genetics ; DNA-Binding Proteins/*physiology ; Gene Expression Regulation ; *Genes ; Humans ; Lymphocytes/*physiology ; *Regulatory Sequences, Nucleic Acid ; Transcription Factors/*physiology
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  • 96
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1988-11-04
    Description: As a way of studying nucleosome assembly and maintenance in Saccharomyces cerevisiae, mutants bearing deletions or duplications of the genes encoding histones H2A and H2B were analyzed. Previous genetic analysis had shown that only one of these mutants exhibited dramatic and pleiotropic phenotypes. This mutant was also the only one that contained disrupted chromatin, suggesting that the original phenotypes were attributable to alterations in chromosome structure. The chromatin disruption in the mutant, however, did not extend over the entire genome, but rather was localized to specific regions. Thus, while the arrangement of nucleosomes over the HIS4 and GAL1 genes, the telomeres, and the long terminal repeats (delta sequences) of Ty retrotransposons appeared essentially normal, nucleosomes over the CYH2 and UBI4 genes and the centromere of chromosome III were dramatically disrupted. The observation that the mutant exhibited localized chromatin disruptions implies that the assembly or maintenance of nucleosomes differs over different parts of the yeast genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Norris, D -- Dunn, B -- Osley, M A -- GM40118/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1988 Nov 4;242(4879):759-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2847314" target="_blank"〉PubMed〈/a〉
    Keywords: Centromere/ultrastructure ; Chromatin/physiology/*ultrastructure ; Chromosome Deletion ; DNA Transposable Elements ; Galactose ; Gene Expression Regulation ; Genes, Fungal ; Histidine ; Histones/*genetics ; Mutation ; Phenotype ; RNA, Messenger/genetics ; Repetitive Sequences, Nucleic Acid ; Saccharomyces cerevisiae/genetics/*ultrastructure ; Transcription, Genetic
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1988-07-08
    Description: Run-on transcription experiments were used to demonstrate that transcription of T cell receptor beta chain V genes is activated by DNA rearrangement, in a manner similar to immunoglobulin genes. A transcriptional enhancer likely to be involved in this activation has been identified. A 25-kilobase region from J beta 1 to V beta 14 was tested for enhancer activity by transient transfections, and an enhancer was found 7.5 kilobases 3' of C beta 2. The beta enhancer has low activity relative to the simian virus 40 viral enhancer, does not display a preference for V beta promoters, has a T cell-specific activity, and binds two purified immunoglobulin heavy chain enhancer factors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDougall, S -- Peterson, C L -- Calame, K -- GM29361/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1988 Jul 8;241(4862):205-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, UCLA School of Medicine 90024.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2968651" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosome Mapping ; *Enhancer Elements, Genetic ; Gene Expression Regulation ; Genes, Immunoglobulin ; Immunoglobulin Heavy Chains/genetics ; In Vitro Techniques ; Mice ; Nuclear Proteins/physiology ; Receptors, Antigen, T-Cell/*genetics ; Receptors, Antigen, T-Cell, alpha-beta ; *Regulatory Sequences, Nucleic Acid ; Transcription Factors/physiology ; Transcription, Genetic
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  • 98
    Publication Date: 1988-07-01
    Description: A method of combinatorial cassette mutagenesis was designed to readily determine the informational content of individual residues in protein sequences. The technique consists of simultaneously randomizing two or three positions by oligonucleotide cassette mutagenesis, selecting for functional protein, and then sequencing to determine the spectrum of allowable substitutions at each position. Repeated application of this method to the dimer interface of the DNA-binding domain of lambda repressor reveals that the number and type of substitutions allowed at each position are extremely variable. At some positions only one or two residues are functionally acceptable; at other positions a wide range of residues and residue types are tolerated. The number of substitutions allowed at each position roughly correlates with the solvent accessibility of the wild-type side chain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reidhaar-Olson, J F -- Sauer, R T -- AI-15706/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1988 Jul 1;241(4861):53-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3388019" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Binding Sites ; Codon ; DNA/genetics/metabolism ; *DNA-Binding Proteins ; Macromolecular Substances ; Molecular Sequence Data ; Mutation ; Plasmids ; Protein Conformation ; Repressor Proteins/*genetics ; Structure-Activity Relationship ; Transcription Factors/*genetics ; Viral Proteins ; Viral Regulatory and Accessory Proteins
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  • 99
    Publication Date: 1988-10-14
    Description: Structural changes of the human retinoblastoma gene have been demonstrated previously in retinoblastoma and some clinically related tumors including osteosarcoma. Structural aberrations of the retinoblastoma locus (RB1) were observed in 25% of breast tumor cell lines studied and 7% of the primary tumors. These changes include homozygous internal deletions and total deletion of RB1; a duplication of an exon was observed in one of the cell lines. In all cases, structural changes either resulted in the absence or truncation of the RB1 transcript. No obvious defect in RB1 was detected by DNA blot analysis in primary tumors or cell lines from Wilms' tumor, cervical carcinoma, or hepatoma. These results further support the concept that the human RB1 gene has pleiotropic effects on specific types of cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉T'Ang, A -- Varley, J M -- Chakraborty, S -- Murphree, A L -- Fung, Y K -- CA44754/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1988 Oct 14;242(4876):263-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology/Oncology, Childrens Hospital of Los Angeles, CA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3175651" target="_blank"〉PubMed〈/a〉
    Keywords: Breast Neoplasms/*genetics ; Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; DNA/genetics ; DNA Probes ; Exons ; Eye Neoplasms/*genetics ; Female ; *Gene Rearrangement ; Homozygote ; Humans ; Lymphatic Metastasis ; Menopause ; Mutation ; Nucleic Acid Hybridization ; Retinoblastoma/*genetics ; Risk Factors ; Tumor Cells, Cultured
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  • 100
    Publication Date: 1988-07-15
    Description: Daily variation has been found in the length of the polyadenylate tail attached to vasopressin messenger RNA in the suprachiasmatic nuclei, which is the location of an endogenous circadian pacemaker in mammals. No such variation was found in the supraoptic or paraventricular nuclei. This variation in the length of the polyadenylate tail may underlie the circadian rhythm of vasopressin peptide levels in cerebrospinal fluid and is a unique example of a daily rhythm in messenger RNA structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robinson, B G -- Frim, D M -- Schwartz, W J -- Majzoub, J A -- 1P50HL36568/HL/NHLBI NIH HHS/ -- R01NS24542/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1988 Jul 15;241(4863):342-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3388044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arginine Vasopressin/*physiology ; Biological Clocks ; Circadian Rhythm ; Gene Expression Regulation ; Poly A/*physiology ; RNA, Messenger/*physiology ; Rats ; Suprachiasmatic Nucleus/*physiology
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