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  • Mice  (225)
  • Geophysics  (202)
  • 2000-2004  (427)
  • 1980-1984
  • 2002  (427)
  • 1
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    In:  J. Geophys. Res., London, Am. Soc. Mech. Eng., vol. 107, no. B7, pp. ESE 4-1 to ESE 4-18, pp. 2147, (ISBN: 0534351875, 2nd edition)
    Publication Date: 2002
    Keywords: Seismology ; Three dimensional ; Dynamic ; Source ; Modelling ; Fracture ; 7209 ; Earthquake ; dynamics ; and ; mechanics ; 3230 ; Mathematical ; Geophysics: ; Numerical ; solutions ; 7260 ; Seismology: ; Theory ; and ; modeling ; 7299 ; 3299 ; Mathematical ; Geophysics ; JGR
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-09-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, John H -- Elledge, Stephen J -- New York, N.Y. -- Science. 2002 Sep 13;297(5588):1822-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228708" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; BRCA1 Protein/metabolism ; BRCA2 Protein/*chemistry/*metabolism ; Binding Sites ; Breast Neoplasms/genetics ; Crystallography, X-Ray ; DNA/*metabolism ; DNA Damage ; *DNA Repair ; DNA, Single-Stranded/metabolism ; DNA-Binding Proteins/metabolism ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Genetic Predisposition to Disease ; Humans ; Mice ; Ovarian Neoplasms/genetics ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Rad51 Recombinase ; Rats ; Recombination, Genetic ; Replication Protein A
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2002-04-16
    Description: Natural killer (NK) cells express inhibitory receptors for major histocompatibility complex (MHC) class I antigens, preventing attack against healthy cells. Mouse cytomegalovirus (MCMV) encodes an MHC-like protein (m157) that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice. In MCMV-resistant mice, this viral protein engages a related activating receptor (Ly49H) and confers host protection. These activating and inhibitory receptors are highly homologous, suggesting the possibility that one evolved from the other in response to selective pressure imposed by the pathogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arase, Hisashi -- Mocarski, Edward S -- Campbell, Ann E -- Hill, Ann B -- Lanier, Lewis L -- AI30363/AI/NIAID NIH HHS/ -- CA89294/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 May 17;296(5571):1323-6. Epub 2002 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11950999" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Antigens, Ly/chemistry/genetics/*immunology/metabolism ; Cell Line ; Coculture Techniques ; Disease Susceptibility ; Evolution, Molecular ; Herpesviridae Infections/*immunology ; Histocompatibility Antigens Class I/immunology ; Hybridomas ; Immunity, Innate ; Interferon-gamma/biosynthesis ; Killer Cells, Natural/*immunology ; Lectins, C-Type ; Ligands ; Lymphocyte Activation ; Membrane Glycoproteins/chemistry/genetics/*immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Muromegalovirus/genetics/*immunology/metabolism ; NK Cell Lectin-Like Receptor Subfamily A ; Protein Binding ; Receptors, Immunologic/chemistry/genetics/*immunology/metabolism ; Receptors, NK Cell Lectin-Like ; Recombinant Fusion Proteins/metabolism ; Transfection ; Viral Proteins/chemistry/genetics/*immunology/metabolism
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  • 4
    Publication Date: 2002-04-06
    Description: Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impaired recruitment of Nbs1, 53bp1, and Brca1, but not Rad51, to irradiation-induced foci. Thus, H2AX is critical for facilitating the assembly of specific DNA-repair complexes on damaged DNA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721576/" 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/PMC4721576/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Celeste, Arkady -- Petersen, Simone -- Romanienko, Peter J -- Fernandez-Capetillo, Oscar -- Chen, Hua Tang -- Sedelnikova, Olga A -- Reina-San-Martin, Bernardo -- Coppola, Vincenzo -- Meffre, Eric -- Difilippantonio, Michael J -- Redon, Christophe -- Pilch, Duane R -- Olaru, Alexandru -- Eckhaus, Michael -- Camerini-Otero, R Daniel -- Tessarollo, Lino -- Livak, Ferenc -- Manova, Katia -- Bonner, William M -- Nussenzweig, Michel C -- Nussenzweig, Andre -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):922-7. Epub 2002 Apr 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934988" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology/physiology ; Base Sequence ; Cell Aging ; Cell Cycle ; Cells, Cultured ; *Chromosome Aberrations ; DNA Damage ; *DNA Repair ; Female ; Gene Targeting ; Histones/chemistry/*genetics/*physiology ; Immunoglobulin Class Switching ; Infertility, Male/genetics/physiopathology ; Lymphocyte Count ; Male ; Meiosis ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Mutation ; Phosphorylation ; *Recombination, Genetic ; Spermatocytes/physiology ; T-Lymphocytes/immunology/physiology
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  • 5
    Publication Date: 2002-07-13
    Description: Full-length poliovirus complementary DNA (cDNA) was synthesized by assembling oligonucleotides of plus and minus strand polarity. The synthetic poliovirus cDNA was transcribed by RNA polymerase into viral RNA, which translated and replicated in a cell-free extract, resulting in the de novo synthesis of infectious poliovirus. Experiments in tissue culture using neutralizing antibodies and CD155 receptor-specific antibodies and neurovirulence tests in CD155 transgenic mice confirmed that the synthetic virus had biochemical and pathogenic characteristics of poliovirus. Our results show that it is possible to synthesize an infectious agent by in vitro chemical-biochemical means solely by following instructions from a written sequence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cello, Jeronimo -- Paul, Aniko V -- Wimmer, Eckard -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1016-8. Epub 2002 Jul 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12114528" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Capsid/metabolism ; Cell-Free System ; DNA, Complementary/*chemical synthesis/genetics ; DNA-Directed RNA Polymerases/genetics ; Female ; *Genome, Viral ; HeLa Cells ; Humans ; Male ; *Membrane Proteins ; Mice ; Mice, Transgenic ; Neutralization Tests ; Poliomyelitis/virology ; *Poliovirus/genetics/immunology/pathogenicity/physiology ; Promoter Regions, Genetic ; Protein Biosynthesis ; RNA, Viral/*chemical synthesis/genetics/physiology ; Receptors, Virus/genetics/immunology/metabolism ; Transcription, Genetic ; Viral Plaque Assay ; Viral Proteins ; Virulence ; Virus Replication
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  • 6
    Publication Date: 2002-05-04
    Description: There is a relation between stress and alcohol drinking. We show that the corticotropin-releasing hormone (CRH) system that mediates endocrine and behavioral responses to stress plays a role in the control of long-term alcohol drinking. In mice lacking a functional CRH1 receptor, stress leads to enhanced and progressively increasing alcohol intake. The effect of repeated stress on alcohol drinking behavior appeared with a delay and persisted throughout life. It was associated with an up-regulation of the N-methyl-d-aspartate receptor subunit NR2B. Alterations in the CRH1 receptor gene and adaptional changes in NR2B subunits may constitute a genetic risk factor for stress-induced alcohol drinking and alcoholism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sillaber, Inge -- Rammes, Gerhard -- Zimmermann, Stephan -- Mahal, Beatrice -- Zieglgansberger, Walter -- Wurst, Wolfgang -- Holsboer, Florian -- Spanagel, Rainer -- New York, N.Y. -- Science. 2002 May 3;296(5569):931-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. sillaber@mpipsykl.mpg.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988580" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; *Alcohol Drinking ; Alcoholism/*etiology/genetics ; Animals ; Brain/metabolism ; Corticotropin-Releasing Hormone/physiology ; Ethanol/blood ; Female ; Hippocampus/physiology ; In Vitro Techniques ; Male ; Mice ; Mice, Knockout ; Models, Animal ; Mutation ; Receptors, AMPA/metabolism ; Receptors, Corticotropin-Releasing Hormone/*genetics/*physiology ; Receptors, Kainic Acid/metabolism ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Signal Transduction ; Stress, Physiological/physiopathology ; Stress, Psychological/*physiopathology ; Up-Regulation
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-05-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, Eliot -- New York, N.Y. -- Science. 2002 May 17;296(5571):1212.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12016275" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Drug Industry/legislation & jurisprudence ; Drug Screening Assays, Antitumor ; Mice ; *Mice, Transgenic ; National Institutes of Health (U.S.)/legislation & jurisprudence ; *Neoplasms, Experimental ; *Patents as Topic ; United States ; Universities/legislation & jurisprudence
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-02-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beckman, Mary -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):782.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823614" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression ; Animals ; *Behavior, Animal ; Cues ; Female ; Male ; Membrane Proteins/*genetics/*physiology ; Mice ; Mice, Knockout ; Neurons/physiology ; Pheromones/*physiology ; Sex Characteristics ; *Sexual Behavior, Animal ; TRPC Cation Channels ; Vomeronasal Organ/*innervation/physiology
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-09-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beckman, Mary -- New York, N.Y. -- Science. 2002 Sep 6;297(5587):1626-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215618" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/*immunology ; Arthritis, Rheumatoid/immunology ; Autoantibodies/immunology ; Humans ; Joints/*immunology ; Mast Cells/immunology ; Mice
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  • 10
    Publication Date: 2002-02-09
    Description: The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gadek, T R -- Burdick, D J -- McDowell, R S -- Stanley, M S -- Marsters, J C Jr -- Paris, K J -- Oare, D A -- Reynolds, M E -- Ladner, C -- Zioncheck, K A -- Lee, W P -- Gribling, P -- Dennis, M S -- Skelton, N J -- Tumas, D B -- Clark, K R -- Keating, S M -- Beresini, M H -- Tilley, J W -- Presta, L G -- Bodary, S C -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1086-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834839" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/pharmacology ; Cyclosporine/pharmacology ; Dermatitis, Irritant/drug therapy ; Dinitrofluorobenzene ; Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Immunosuppressive Agents/chemical synthesis/chemistry/metabolism/*pharmacology ; Intercellular Adhesion Molecule-1/chemistry/*immunology/*metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Mutagenesis ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thiophenes/*chemical synthesis/chemistry/metabolism/*pharmacology ; beta-Alanine/analogs & derivatives/*chemical ; synthesis/chemistry/metabolism/*pharmacology
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  • 11
    Publication Date: 2002-11-16
    Description: Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid follicles (ILFs) associated with a 100-fold expansion of anaerobic flora in the small intestine. Reduction of bacterial flora by antibiotic treatment of AID-/- mice abolished ILF hyperplasia as well as the germinal center enlargement seen in secondary lymphoid tissues. Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fagarasan, Sidonia -- Muramatsu, Masamichi -- Suzuki, Keiichiro -- Nagaoka, Hitoshi -- Hiai, Hiroshi -- Honjo, Tasuku -- New York, N.Y. -- Science. 2002 Nov 15;298(5597):1424-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12434060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents ; B-Lymphocytes/immunology ; Bacteria, Aerobic/*growth & development ; Bacteria, Anaerobic/*growth & development ; Cell Division ; Colony Count, Microbial ; Cytidine Deaminase/genetics/*metabolism ; Dendritic Cells, Follicular/immunology ; Drug Therapy, Combination/pharmacology ; Genes, Immunoglobulin ; Germinal Center/immunology ; Homeostasis ; Hyperplasia ; Immunization ; Immunoglobulin Class Switching ; Immunoglobulin Variable Region/genetics ; Intestine, Small/immunology/*microbiology ; Lymphocyte Activation ; Lymphoid Tissue/immunology/*pathology ; Metronidazole/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Peyer's Patches/pathology ; Somatic Hypermutation, Immunoglobulin ; T-Lymphocytes/immunology
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  • 12
    Publication Date: 2002-12-10
    Description: The formation and patterning of mesoderm during mammalian gastrulation require the activity of Nodal, a secreted mesoderm-inducing factor of the transforming growth factor-beta (TGF-beta) family. Here we show that the transcriptional corepressor DRAP1 has a very specific role in regulation of Nodal activity during mouse embryogenesis. We find that loss of Drap1 leads to severe gastrulation defects that are consistent with increased expression of Nodal and can be partially suppressed by Nodal heterozygosity. Biochemical studies indicate that DRAP1 interacts with and inhibits DNA binding by the winged-helix transcription factor FoxH1 (FAST), a critical component of a positive feedback loop for Nodal activity. We propose that DRAP1 limits the spread of a morphogenetic signal by down-modulating the response to the Nodal autoregulatory loop.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iratni, Rabah -- Yan, Yu-Ting -- Chen, Canhe -- Ding, Jixiang -- Zhang, Yi -- Price, Sandy M -- Reinberg, Danny -- Shen, Michael M -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):1996-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Biochemistry, Division of Nucleic Acids Enzymology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471260" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Cell Line ; Crosses, Genetic ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; *Embryonic and Fetal Development ; Female ; Forkhead Transcription Factors ; Gastrula/*physiology ; Gene Expression Regulation, Developmental ; Gene Targeting ; Heterozygote ; In Situ Hybridization ; Left-Right Determination Factors ; Male ; Mesoderm/cytology/physiology ; Mice ; Morphogenesis ; Mutation ; Nodal Protein ; Phenotype ; Protein Binding ; RNA Interference ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; *Signal Transduction ; Transcription Factors/metabolism ; Transforming Growth Factor beta/genetics/*metabolism
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  • 13
    Publication Date: 2002-06-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Copeland, Neal G -- Jenkins, Nancy A -- O'Brien, Stephen J -- New York, N.Y. -- Science. 2002 May 31;296(5573):1617-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD, 21702, USA. copeland@ncifcrf.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12040165" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Biological Evolution ; Chromosome Aberrations ; Chromosomes/*genetics ; Chromosomes, Human/genetics ; Computational Biology ; Conserved Sequence ; Evolution, Molecular ; Gene Duplication ; Gene Rearrangement ; Genes ; Genome ; *Genome, Human ; Genomics ; Humans ; Mice ; Mice, Inbred Strains/*genetics ; Multigene Family ; *Sequence Analysis, DNA ; Species Specificity ; Synteny
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-02-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Darvasi, A -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2423.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Evolution Systematicsand Ecology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. arield@cc.huji.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11865449" target="_blank"〉PubMed〈/a〉
    Keywords: *Algorithms ; Animals ; Chromosome Mapping/*methods ; Genetic Variation ; Genotype ; Mice ; Mice, Inbred Strains ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable
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  • 15
    Publication Date: 2002-08-31
    Description: Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berman, David M -- Karhadkar, Sunil S -- Hallahan, Andrew R -- Pritchard, Joel I -- Eberhart, Charles G -- Watkins, D Neil -- Chen, James K -- Cooper, Michael K -- Taipale, Jussi -- Olson, James M -- Beachy, Philip A -- New York, N.Y. -- Science. 2002 Aug 30;297(5586):1559-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12202832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*therapeutic use ; Bicuculline/*therapeutic use ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cerebellar Neoplasms/*drug therapy ; Disease Models, Animal ; Hedgehog Proteins ; Humans ; Medulloblastoma/*drug therapy ; Membrane Proteins/genetics ; Mice ; Mice, Nude ; Receptors, Cell Surface ; Signal Transduction/drug effects ; Trans-Activators/*antagonists & inhibitors/metabolism ; Tumor Cells, Cultured
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-12-03
    Description: The gastric pathogen Helicobacter pylori is known to be able to use molecular hydrogen as a respiratory substrate when grown in the laboratory. We found that hydrogen is available in the gastric mucosa of mice and that its use greatly increased the stomach colonization by H. pylori. Hydrogenase activity in H. pylori is constitutive but increased fivefold upon incubation with hydrogen. Hydrogen concentrations measured in the stomachs of live mice were found to be 10 to 50 times as high as the H. pylori affinity for hydrogen. A hydrogenase mutant strain is much less efficient in its colonization of mice. Therefore, hydrogen present in animals as a consequence of normal colonic flora is an energy-yielding substrate that can facilitate the maintenance of a pathogenic bacterium.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Olson, Jonathan W -- Maier, Robert J -- New York, N.Y. -- Science. 2002 Nov 29;298(5599):1788-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, University of Georgia, Athens, GA 30602, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12459589" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catechol 2,3-Dioxygenase ; Colon/metabolism/microbiology ; *Dioxygenases ; Energy Metabolism ; Fermentation ; Gastric Mucosa/*metabolism/*microbiology ; Gene Expression Regulation, Bacterial ; Genes, Reporter ; Helicobacter pylori/growth & development/*metabolism ; Hydrogen/*metabolism ; Hydrogenase/genetics/*metabolism ; Kinetics ; Mice ; Mutation ; Oxidation-Reduction ; Oxygenases/genetics/metabolism ; Transcription, Genetic
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  • 17
    Publication Date: 2002-07-06
    Description: The enzymatic conjugation of arginine to the N-termini of proteins is a part of the ubiquitin-dependent N-end rule pathway of protein degradation. In mammals, three N-terminal residues-aspartate, glutamate, and cysteine-are substrates for arginylation. The mouse ATE1 gene encodes a family of Arg-tRNA-protein transferases (R-transferases) that mediate N-terminal arginylation. We constructed ATE1-lacking mouse strains and found that ATE1-/- embryos die with defects in heart development and in angiogenic remodeling of the early vascular plexus. Through biochemical analyses, we show that N-terminal cysteine, in contrast to N-terminal aspartate and glutamate, is oxidized before its arginylation by R-transferase, suggesting that the arginylation branch of the N-end rule pathway functions as an oxygen sensor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwon, Yong Tae -- Kashina, Anna S -- Davydov, Ilia V -- Hu, Rong-Gui -- An, Jee Young -- Seo, Jai Wha -- Du, Fangyong -- Varshavsky, Alexander -- GM31530/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 5;297(5578):96-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, 147-75, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12098698" target="_blank"〉PubMed〈/a〉
    Keywords: Alkylation ; Aminoacyltransferases/*genetics/*metabolism ; Animals ; Aorta/embryology ; Arginine/*metabolism ; Aspartic Acid/metabolism ; Blood Vessels/*embryology ; Cell Line ; Cysteic Acid/metabolism ; Cysteine/metabolism ; Female ; Glutamic Acid/metabolism ; Heart/*embryology ; Heart Defects, Congenital/embryology ; Heart Septal Defects/embryology ; Hypoxia-Inducible Factor 1, alpha Subunit ; Male ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic ; Oxidation-Reduction ; Proteins/*metabolism ; Pulmonary Artery/embryology ; RGS Proteins/metabolism ; Recombinant Proteins/metabolism ; Sulfinic Acids/metabolism ; Transcription Factors/metabolism ; Transfection
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  • 18
    Publication Date: 2002-08-10
    Description: Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhalla, Upinder S -- Ram, Prahlad T -- Iyengar, Ravi -- CA-79134/CA/NCI NIH HHS/ -- CA-81050/CA/NCI NIH HHS/ -- GM-54508/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1018-23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Biological Sciences, Bangalore 560065 India. bhalla@ncbs.res.in〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12169734" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Adaptation, Physiological ; Animals ; *Cell Cycle Proteins ; Computer Simulation ; Dose-Response Relationship, Drug ; Dual Specificity Phosphatase 1 ; *Feedback, Physiological ; Immediate-Early Proteins/*metabolism ; *MAP Kinase Signaling System ; Mathematics ; Mice ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Phospholipases A/antagonists & inhibitors/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Protein Phosphatase 1 ; Protein Tyrosine Phosphatases/*metabolism
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  • 19
    Publication Date: 2002-09-14
    Description: Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Haijuan -- Jeffrey, Philip D -- Miller, Julie -- Kinnucan, Elspeth -- Sun, Yutong -- Thoma, Nicolas H -- Zheng, Ning -- Chen, Phang-Lang -- Lee, Wen-Hwa -- Pavletich, Nikola P -- New York, N.Y. -- Science. 2002 Sep 13;297(5588):1837-48.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228710" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; BRCA2 Protein/*chemistry/genetics/*metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA/metabolism ; *DNA Repair ; DNA, Single-Stranded/*metabolism ; DNA-Binding Proteins/metabolism ; Genes, BRCA2 ; Helix-Turn-Helix Motifs ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Mice ; Molecular Sequence Data ; Mutation ; Proteasome Endopeptidase Complex ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; Rad51 Recombinase ; Rats ; *Recombination, Genetic
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2120-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12077376" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Transplantation ; Epithelial Cells/cytology/transplantation ; Kidney ; Mice ; Mice, Nude ; Stem Cell Transplantation ; Stem Cells/*physiology ; T-Lymphocytes/cytology/*immunology ; Thymus Gland/*cytology/growth & development/*immunology
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  • 21
    Publication Date: 2002-11-02
    Description: beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biragyn, Arya -- Ruffini, Pier Adelchi -- Leifer, Cynthia A -- Klyushnenkova, Elena -- Shakhov, Alexander -- Chertov, Oleg -- Shirakawa, Aiko K -- Farber, Joshua M -- Segal, David M -- Oppenheim, Joost J -- Kwak, Larry W -- N0L-CO-12400/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 1;298(5595):1025-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. arya@mail.ncifcrf.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12411706" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/immunology ; Cancer Vaccines/immunology ; Cell Line ; Cytokines/biosynthesis ; Dendritic Cells/*immunology ; *Drosophila Proteins ; Female ; Humans ; Interferon-alpha/physiology ; Ligands ; Lipopolysaccharides/immunology/pharmacology ; Lymphocyte Culture Test, Mixed ; Membrane Glycoproteins/genetics/*physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Neoplasms/immunology/therapy ; Receptors, CCR6 ; Receptors, Cell Surface/genetics/*physiology ; Receptors, Chemokine/metabolism ; Recombinant Fusion Proteins/pharmacology ; Signal Transduction ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Transfection ; beta-Defensins/pharmacology/*physiology
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  • 22
    Publication Date: 2002-04-27
    Description: Lymphatic metastasis contributes to mortality from solid tumors. Whether metastasizing cancer cells reach lymph nodes via intratumor lymphatic vessels is unknown. Here, we examine functional lymphatics associated with mouse tumors expressing normal or elevated levels of vascular endothelial growth factor-C (VEGF-C), a molecule that stimulates lymphangiogenesis. Although VEGF-C overexpression increased lymphatic surface area in the tumor margin and lymphatic metastasis, these tumors contained no functional lymphatics, as assessed by four independent functional assays and immunohistochemical staining. These findings suggest that the functional lymphatics in the tumor margin alone are sufficient for lymphatic metastasis and should be targeted therapeutically.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Padera, Timothy P -- Kadambi, Ananth -- di Tomaso, Emmanuelle -- Carreira, Carla Mouta -- Brown, Edward B -- Boucher, Yves -- Choi, Noah C -- Mathisen, Douglas -- Wain, John -- Mark, Eugene J -- Munn, Lance L -- Jain, Rakesh K -- R24-CA85140/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 7;296(5574):1883-6. Epub 2002 Apr 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉E. L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11976409" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/chemistry/pathology ; Animals ; Antigens, Surface/analysis ; Endothelial Growth Factors/metabolism ; Extracellular Space/physiology ; Fibrosarcoma/metabolism/*pathology/physiopathology/secondary ; Glycoproteins/analysis ; Humans ; Immunohistochemistry ; Lung Neoplasms/chemistry/pathology/physiopathology/secondary ; *Lymphatic Metastasis ; Lymphatic System/chemistry/*pathology/physiology ; Lymphography ; Melanoma, Experimental/metabolism/*pathology/physiopathology/secondary ; Mice ; Mice, Inbred C3H ; Mice, Nude ; Microscopy/methods ; Neoplasm Transplantation ; Neoplasms/metabolism/*pathology/physiopathology ; Pressure ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor C ; Vesicular Transport Proteins
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-04-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2002 Apr 5;296(5565):28-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11934996" target="_blank"〉PubMed〈/a〉
    Keywords: Amyloid beta-Peptides/chemistry ; Animals ; Humans ; Mice ; Protein Conformation ; *Protein Folding ; *Protein Structure, Quaternary ; Proteins/*chemistry ; Rats
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  • 24
    Publication Date: 2002-02-23
    Description: The p53 tumor suppressor gene is inactivated in the majority of human cancers. Tumor cells deficient in p53 display a diminished rate of apoptosis under hypoxic conditions, a circumstance that might reduce their reliance on vascular supply, and hence their responsiveness to antiangiogenic therapy. Here, we report that mice bearing tumors derived from p53(-/-) HCT116 human colorectal cancer cells were less responsive to antiangiogenic combination therapy than mice bearing isogenic p53(+/+) tumors. Thus, although antiangiogenic therapy targets genetically stable endothelial cells in the tumor vasculature, genetic alterations that decrease the vascular dependence of tumor cells can influence the therapeutic response of tumors to this therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Joanne L -- Rak, Janusz W -- Coomber, Brenda L -- Hicklin, Daniel J -- Kerbel, Robert S -- CA-41233/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1526-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sunnybrook and Women's College Health Sciences Centre, Molecular and Cellular Biology Research, Room S-218, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11859195" target="_blank"〉PubMed〈/a〉
    Keywords: Angiogenesis Inhibitors/pharmacology/*therapeutic use ; Animals ; Antibodies/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Apoptosis ; *Cell Hypoxia ; Cell Survival ; Colorectal Neoplasms ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/genetics/metabolism ; Gene Deletion ; *Gene Silencing ; *Genes, p53 ; Humans ; In Situ Nick-End Labeling ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Neoplasms, Experimental/blood supply/*drug therapy/*genetics/pathology ; Receptor Protein-Tyrosine Kinases/immunology ; Receptors, Growth Factor/immunology ; Receptors, Vascular Endothelial Growth Factor ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/metabolism ; Vinblastine/therapeutic use
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-03-02
    Description: Although ligand activation of receptor signaling is well understood, less is known about how a cell switches off signaling by the activated receptor. In his Perspective, Gill discusses new work (Haj et al.) that visualizes one step in the process of deactivating a ligand-activated receptor tyrosine kinase--the dephosphorylation of the internalized receptor by a phosphatase in the endoplasmic reticulum.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gill, Gordon N -- New York, N.Y. -- Science. 2002 Mar 1;295(5560):1654-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California, San Diego, La Jolla, CA 92093-0650, USA. ggill@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872824" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/enzymology ; Endocytosis ; Endoplasmic Reticulum/*enzymology ; Endosomes/enzymology/metabolism ; Energy Transfer ; Fluorescence ; Ligands ; Lysosomes/metabolism ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Protein Transport ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; Protein Tyrosine Phosphatases/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-cbl ; Receptor Protein-Tyrosine Kinases/chemistry/*metabolism ; Receptor, Epidermal Growth Factor/chemistry/*metabolism ; Receptors, Platelet-Derived Growth Factor/chemistry/*metabolism ; Ubiquitin/metabolism ; *Ubiquitin-Protein Ligases
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  • 26
    Publication Date: 2002-05-11
    Description: Aneuploidy (trisomy or monosomy) is the leading genetic cause of pregnancy loss in humans and results from errors in meiotic chromosome segregation. Here, we show that the absence of synaptonemal complex protein 3 (SCP3) promotes aneuploidy in murine oocytes by inducing defective meiotic chromosome segregation. The abnormal oocyte karyotype is inherited by embryos, which die in utero at an early stage of development. In addition, embryo death in SCP3-deficient females increases with advancing maternal age. We found that SCP3 is required for chiasmata formation and for the structural integrity of meiotic chromosomes, suggesting that altered chromosomal structure triggers nondisjunction. SCP3 is thus linked to inherited aneuploidy in female germ cells and provides a model system for studying age-dependent degeneration in oocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yuan, Li -- Liu, Jian-Guo -- Hoja, Mary-Rose -- Wilbertz, Johannes -- Nordqvist, Katarina -- Hoog, Christer -- New York, N.Y. -- Science. 2002 May 10;296(5570):1115-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genomics and Bioinformatics and Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12004129" target="_blank"〉PubMed〈/a〉
    Keywords: *Aneuploidy ; Animals ; Chromosome Segregation ; Chromosomes/*physiology/ultrastructure ; Crossing Over, Genetic ; *Embryo Loss ; Female ; Karyotyping ; Litter Size ; Male ; Maternal Age ; *Meiosis ; Mice ; Mice, Inbred C57BL ; Mutation ; Nondisjunction, Genetic ; Nuclear Proteins/genetics/*physiology ; Oocytes/*physiology ; Pregnancy ; Recombination, Genetic ; Synaptonemal Complex/physiology/ultrastructure
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  • 27
    Publication Date: 2002-05-23
    Description: Mechanical and thermal cues stimulate a specialized group of sensory neurons that terminate in the skin. Three members of the transient receptor potential (TRP) family of channels are expressed in subsets of these neurons and are activated at distinct physiological temperatures. Here, we describe the cloning and characterization of a novel thermosensitive TRP channel. TRPV3 has a unique threshold: It is activated at innocuous (warm) temperatures and shows an increased response at noxious temperatures. TRPV3 is specifically expressed in keratinocytes; hence, skin cells are capable of detecting heat via molecules similar to those in heat-sensing neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peier, Andrea M -- Reeve, Alison J -- Andersson, David A -- Moqrich, Aziz -- Earley, Taryn J -- Hergarden, Anne C -- Story, Gina M -- Colley, Sian -- Hogenesch, John B -- McIntyre, Peter -- Bevan, Stuart -- Patapoutian, Ardem -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2046-9. Epub 2002 May 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12016205" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Newborn ; Blotting, Northern ; CHO Cells ; Capsaicin/*analogs & derivatives/pharmacology ; *Cation Transport Proteins ; Cell Line ; Cells, Cultured ; Cloning, Molecular ; Cricetinae ; Epidermis/cytology/innervation/metabolism ; Ganglia, Spinal/metabolism ; *Hot Temperature ; Humans ; In Situ Hybridization ; Ion Channels/chemistry/genetics/*metabolism ; Keratinocytes/*metabolism ; Membrane Potentials ; Mice ; Molecular Sequence Data ; Nerve Endings/physiology ; Neurons/physiology ; Patch-Clamp Techniques ; RNA, Messenger/genetics/metabolism ; Ruthenium Red/pharmacology ; Signal Transduction ; Spinal Cord/metabolism ; TRPV Cation Channels ; Temperature
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  • 28
    Publication Date: 2002-01-19
    Description: Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor beta (ERbeta)-deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERbeta-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERbeta-deficient mice. Vascular smooth muscle cells isolated from ERbeta-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERbeta-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERbeta in the regulation of vascular function and blood pressure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Yan -- Bian, Zhao -- Lu, Ping -- Karas, Richard H -- Bao, Lin -- Cox, Daniel -- Hodgin, Jeffrey -- Shaul, Philip W -- Thoren, Peter -- Smithies, Oliver -- Gustafsson, Jan-Ake -- Mendelsohn, Michael E -- GM20069/GM/NIGMS NIH HHS/ -- HD30276/HD/NICHD NIH HHS/ -- HL53546/HL/NHLBI NIH HHS/ -- HL56235/HL/NHLBI NIH HHS/ -- P50 HL63494/HL/NHLBI NIH HHS/ -- R01 HL55309/HL/NHLBI NIH HHS/ -- R01 HL56069/HL/NHLBI NIH HHS/ -- R01 HL61298/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Jan 18;295(5554):505-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Cardiology Research Institute, New England Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11799247" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic alpha-Agonists/pharmacology ; Animals ; Aorta ; Blood Pressure ; Cells, Cultured ; Estradiol/*analogs & derivatives/pharmacology ; Estrogen Antagonists/pharmacology ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Guanidines/pharmacology ; Humans ; Hypertension/*physiopathology ; In Vitro Techniques ; Male ; Mice ; Mice, Knockout ; Muscle, Smooth, Vascular/*physiology ; Nitric Oxide Synthase/genetics/metabolism ; Nitric Oxide Synthase Type II ; Nitroarginine/pharmacology ; Patch-Clamp Techniques ; Phenylephrine/pharmacology ; Potassium Channels/metabolism ; Receptors, Estrogen/genetics/*physiology ; *Vasoconstriction/drug effects
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  • 29
    Publication Date: 2002-05-04
    Description: Neurofibromatosis type 1 (NF1) is one of the most prevalent dominantly inherited genetic diseases of the nervous system. NF1 encodes a tumor suppressor whose functional loss results in the development of benign neurofibromas that can progress to malignancy. Neurofibromas are complex tumors composed of axonal processes, Schwann cells, fibroblasts, perineurial cells, and mast cells. Through use of a conditional (cre/lox) allele, we show that loss of NF1 in the Schwann cell lineage is sufficient to generate tumors. In addition, complete NF1-mediated tumorigenicity requires both a loss of NF1 in cells destined to become neoplastic as well as heterozygosity in non-neoplastic cells. The requirement for a permissive haploinsufficient environment to allow tumorigenesis may have therapeutic implications for NF1 and other familial cancers.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024710/" 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/PMC3024710/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, Yuan -- Ghosh, Pritam -- Charnay, Patrick -- Burns, Dennis K -- Parada, Luis F -- R01 NS034296/NS/NINDS NIH HHS/ -- R01 NS034296-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 May 3;296(5569):920-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Developmental Biology, Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9133, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988578" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Axons/ultrastructure ; Cell Lineage ; Cell Transformation, Neoplastic ; Cells, Cultured ; Cranial Nerves/pathology ; Culture Techniques ; Female ; *Genes, Neurofibromatosis 1 ; Genotype ; Heterozygote ; Hyperplasia ; Loss of Heterozygosity ; Male ; Mast Cells/chemistry/pathology ; Mice ; Mice, Transgenic ; Neurofibroma/genetics/*pathology ; Neurofibromatosis 1/genetics/*pathology ; Peripheral Nerves/pathology ; Schwann Cells/chemistry/*pathology ; Spinal Nerves/pathology
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  • 30
    Publication Date: 2002-09-21
    Description: Persons with the autosomal recessive disorder Bloom syndrome are predisposed to cancers of many types due to loss-of-function mutations in the BLM gene, which encodes a recQ-like helicase. Here we show that mice heterozygous for a targeted null mutation of Blm, the murine homolog of BLM, develop lymphoma earlier than wild-type littermates in response to challenge with murine leukemia virus and develop twice the number of intestinal tumors when crossed with mice carrying a mutation in the Apc tumor suppressor. These observations indicate that Blm is a modifier of tumor formation in the mouse and that Blm haploinsufficiency is associated with tumor predisposition, a finding with important implications for cancer risk in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goss, Kathleen Heppner -- Risinger, Mary A -- Kordich, Jennifer J -- Sanz, Maureen M -- Straughen, Joel E -- Slovek, Lisa E -- Capobianco, Anthony J -- German, James -- Boivin, Gregory P -- Groden, Joanna -- CA63507/CA/NCI NIH HHS/ -- CA84291/CA/NCI NIH HHS/ -- CA88460/CA/NCI NIH HHS/ -- ES06096/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):2051-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Department of Molecular Genetics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242442" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoma/genetics/pathology ; Adenosine Triphosphatases/*genetics ; Alleles ; Animals ; Bloom Syndrome/*genetics ; Cells, Cultured ; Crosses, Genetic ; DNA Helicases/*genetics ; Female ; Gene Targeting ; Genes, APC ; *Genetic Predisposition to Disease ; *Heterozygote ; Humans ; Intestinal Neoplasms/*genetics/pathology ; Leukemia Virus, Murine ; Loss of Heterozygosity ; Lymphoma, T-Cell/*genetics/virology ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; RecQ Helicases ; Sister Chromatid Exchange
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  • 31
    Publication Date: 2002-08-24
    Description: The mammalian ovarian follicle consists of a multilayered complex of somatic cells that surround the oocyte. A signal from the follicle cells keeps the oocyte cell cycle arrested at prophase of meiosis I until luteinizing hormone from the pituitary acts on the follicle cells to release the arrest, causing meiosis to continue. Here we show that meiotic arrest can be released in mice by microinjecting the oocyte within the follicle with an antibody that inhibits the stimulatory heterotrimeric GTP-binding protein Gs. This indicates that Gs activity in the oocyte is required to maintain meiotic arrest within the ovarian follicle and suggests that the follicle may keep the cell cycle arrested by activating Gs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mehlmann, Lisa M -- Jones, Teresa L Z -- Jaffe, Laurinda A -- New York, N.Y. -- Science. 2002 Aug 23;297(5585):1343-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Connecticut Health Center, Farmington, CT 06032, USA. lmehlman@neuron.uchc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193786" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology ; Cells, Cultured ; Cyclic AMP/metabolism ; Female ; GTP-Binding Protein alpha Subunits, Gi-Go/immunology/physiology ; GTP-Binding Protein alpha Subunits, Gs/antagonists & ; inhibitors/immunology/*physiology ; Hypoxanthine/pharmacology ; *Meiosis ; Mice ; Oocytes/drug effects/metabolism/*physiology ; Ovarian Follicle/*physiology ; Signal Transduction
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  • 32
    Publication Date: 2002-09-21
    Description: The delivery of CD4 help to CD8+ T cell responses requires interactions between CD40 and CD40 ligand and is thought to occur through antigen-presenting cell (APC) activation. Here we show that generation of memory CD8+ T cells displaying an enhanced capacity for cell division and cytokine secretion required CD4 help but not CD40 expression by the APCs. Activated CD4+ and CD8+ T cells expressed CD40; and in the absence of this protein, CD8+ T cells were unable to differentiate into memory cells or receive CD4 help. These results suggest that, like B cells, CD8+ T cells receive CD4 help directly through CD40 and that this interaction is fundamental for CD8+ T cell memory generation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bourgeois, Christine -- Rocha, Benedita -- Tanchot, Corinne -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):2060-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM U345, Institut Necker, 156 Rue de Vaugirard, F-75730 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242444" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen Presentation ; Antigen-Presenting Cells/immunology ; Antigens/immunology ; Antigens, CD40/genetics/*immunology/*metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD40 Ligand/metabolism ; CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism ; Cell Differentiation ; Cell Division ; Female ; *Immunologic Memory ; Interferon-gamma/secretion ; Interleukin-2/secretion ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocyte Subsets/cytology/*immunology/metabolism
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  • 33
    Publication Date: 2002-05-25
    Description: Mice and cattle with genetic deficiencies in myostatin exhibit dramatic increases in skeletal muscle mass, suggesting that myostatin normally suppresses muscle growth. Whether this increased muscling results from prenatal or postnatal lack of myostatin activity is unknown. Here we show that myostatin circulates in the blood of adult mice in a latent form that can be activated by acid treatment. Systemic overexpression of myostatin in adult mice was found to induce profound muscle and fat loss analogous to that seen in human cachexia syndromes. These data indicate that myostatin acts systemically in adult animals and may be a useful pharmacologic target in clinical settings such as cachexia, where muscle growth is desired.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmers, Teresa A -- Davies, Monique V -- Koniaris, Leonidas G -- Haynes, Paul -- Esquela, Aurora F -- Tomkinson, Kathy N -- McPherron, Alexandra C -- Wolfman, Neil M -- Lee, Se-Jin -- 5 T32 CA09139/CA/NCI NIH HHS/ -- R01 CA88866/CA/NCI NIH HHS/ -- R01 HD35887/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2002 May 24;296(5572):1486-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12029139" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Activins/administration & dosage/pharmacology ; Adipose Tissue/anatomy & histology/pathology ; Animals ; Body Weight ; CHO Cells ; Cachexia/*etiology/metabolism/pathology ; Cricetinae ; Eating ; Female ; Follistatin ; Liver/anatomy & histology/pathology ; Mice ; Mice, Nude ; Muscle Fibers, Skeletal/cytology/pathology ; Muscle, Skeletal/*anatomy & histology/pathology ; Myostatin ; Organ Size ; Peptide Fragments/administration & dosage/pharmacology ; Recombinant Proteins/administration & dosage ; Transforming Growth Factor beta/administration & dosage/blood/*physiology ; Wasting Syndrome/etiology/metabolism/pathology ; Weight Loss
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  • 34
    Publication Date: 2002-04-16
    Description: One of the factors postulated to drive the aging process is the accumulation of DNA damage. Here, we provide strong support for this hypothesis by describing studies of mice with a mutation in XPD, a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder trichothiodystrophy (TTD). TTD mice were found to exhibit many symptoms of premature aging, including osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, infertility, and reduced life-span. TTD mice carrying an additional mutation in XPA, which enhances the DNA repair defect, showed a greatly accelerated aging phenotype, which correlated with an increased cellular sensitivity to oxidative DNA damage. We hypothesize that aging in TTD mice is caused by unrepaired DNA damage that compromises transcription, leading to functional inactivation of critical genes and enhanced apoptosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Boer, Jan -- Andressoo, Jaan Olle -- de Wit, Jan -- Huijmans, Jan -- Beems, Rudolph B -- van Steeg, Harry -- Weeda, Geert -- van der Horst, Gijsbertus T J -- van Leeuwen, Wibeke -- Themmen, Axel P N -- Meradji, Morteza -- Hoeijmakers, Jan H J -- AG 17242-02/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2002 May 17;296(5571):1276-9. Epub 2002 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Genetics Center, Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus University, 3000 DR Rotterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11950998" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Aging, Premature/*etiology ; Animals ; Apoptosis ; Bone Density ; Cachexia/etiology ; Crosses, Genetic ; *DNA Damage ; DNA Helicases/genetics/*physiology ; *DNA Repair ; DNA-Binding Proteins/genetics/physiology ; Female ; Fertility ; Gene Targeting ; Growth Disorders/etiology/genetics ; Hair Diseases/genetics ; Kyphosis/etiology/genetics/pathology ; Male ; Mice ; Mutation ; Oxidative Stress ; Phenotype ; Point Mutation ; Proteins/genetics/*physiology ; RNA-Binding Proteins/genetics/physiology ; *Transcription Factors ; Transcription, Genetic ; Xeroderma Pigmentosum Group A Protein ; Xeroderma Pigmentosum Group D Protein
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  • 35
    Publication Date: 2002-05-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2002 May 10;296(5570):1010-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12004102" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Cartilage/growth & development/metabolism ; Chloroplasts/physiology ; Chondrocytes/physiology ; *Developmental Biology ; *Diet ; Dinoflagellida/genetics/physiology ; *Eye ; Eye Proteins ; Folic Acid/administration & dosage ; Homeodomain Proteins/genetics/physiology ; Humans ; Light ; Mice ; Mice, Transgenic ; *Mutation ; Paired Box Transcription Factors ; Planarians/genetics/physiology ; Regeneration ; Repressor Proteins
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-03-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2002 Mar 8;295(5561):1809-11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11884722" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/therapeutic use ; Blindness/etiology ; Eye/immunology/parasitology/*pathology ; Female ; Helminth Proteins/physiology ; Humans ; Keratitis ; Mice ; Microfilaria/immunology/physiology ; Onchocerca volvulus/growth & development/immunology/*microbiology/pathogenicity ; Onchocerciasis, Ocular/drug therapy/*immunology/*microbiology/parasitology ; Wolbachia/immunology/*pathogenicity/physiology
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  • 37
    Publication Date: 2002-03-02
    Description: When bound by extracellular ligands, receptor tyrosine kinases (RTKs) on the cell surface transmit critical signals to the cell interior. Although signal termination is less well understood, protein tyrosine phosphatase-1B (PTP1B) is implicated in the dephosphorylation and inactivation of several RTKs. However, PTP1B resides on the cytoplasmic surface of the endoplasmic reticulum (ER), so how and when it accesses RTKs has been unclear. Using fluorescence resonance energy transfer (FRET) methods, we monitored interactions between the epidermal- and platelet-derived growth factor receptors and PTP1B. PTP1B-catalyzed dephosphorylation required endocytosis of the receptors and occurred at specific sites on the surface of the ER. Most of the RTKs activated at the cell surface showed interaction with PTP1B after internalization, establishing that RTK activation and inactivation are spatially and temporally partitioned within cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haj, Fawaz G -- Verveer, Peter J -- Squire, Anthony -- Neel, Benjamin G -- Bastiaens, Philippe I H -- R01 CA49152/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 1;295(5560):1708-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel-Deaconess Medical Center, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872838" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Catalytic Domain ; Cell Membrane/enzymology ; Cells, Cultured ; *Endocytosis ; Endoplasmic Reticulum/*enzymology ; Energy Transfer ; Epidermal Growth Factor/metabolism/pharmacology ; Fluorescence ; Mice ; Microscopy, Confocal ; Microscopy, Fluorescence ; Phosphorylation ; Platelet-Derived Growth Factor/metabolism/pharmacology ; Protein Transport ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; Protein Tyrosine Phosphatases/chemistry/genetics/*metabolism ; Receptor, Epidermal Growth Factor/*metabolism ; Receptors, Platelet-Derived Growth Factor/*metabolism ; Recombinant Fusion Proteins/metabolism ; Signal Transduction
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  • 38
    Publication Date: 2002-12-03
    Description: Major histocompatibility complex (mhc)-encoded molecules govern immune responses by presenting antigenic peptides to T cells. The extensive polymorphism of genes encoding these molecules is believed to enhance immune defense by broadening the array of antigenic peptides available for T cell recognition, but direct evidence supporting the importance of this mechanism in combating pathogens is limited. Here we link mhc polymorphism-driven diversification of the cytotoxic T lymphocyte (CTL) repertoire to the generation of high-avidity, protective antiviral T cells and to superior antiviral defense. Thus, much of the beneficial effect of the mhc polymorphism in immune defense may be due to its critical influence on the properties of the selected CTL repertoire.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Messaoudi, Ilhem -- Guevara Patino, Jose A -- Dyall, Ruben -- LeMaoult, Joel -- Nikolich-Zugich, Janko -- CA-86803/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Nov 29;298(5599):1797-800.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12459592" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Complementarity Determining Regions ; Cytotoxicity, Immunologic ; Female ; *Genes, MHC Class I ; H-2 Antigens/genetics/*immunology ; Herpes Simplex/*immunology ; Herpesvirus 1, Human/*immunology ; Immunity, Innate ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; *Polymorphism, Genetic ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocytes, Cytotoxic/*immunology
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  • 39
    Publication Date: 2002-06-18
    Description: The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (TH) cells that chronically produced type 2 cytokines in large amounts. This exaggerated TH2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of TH cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aguado, Enrique -- Richelme, Sylvie -- Nunez-Cruz, Selene -- Miazek, Arkadiusz -- Mura, Anne-Marie -- Richelme, Mireille -- Guo, Xiao-Jun -- Sainty, Danielle -- He, Hai-Tao -- Malissen, Bernard -- Malissen, Marie -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2036-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy, INSERM- and CNRS-Universite de la Mediterranee, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12065839" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Antigens, CD5/analysis/metabolism ; B-Lymphocytes/immunology/physiology ; CD4-Positive T-Lymphocytes/immunology/physiology ; CD8-Positive T-Lymphocytes/immunology/physiology ; Carrier Proteins/*genetics/*physiology ; Cell Cycle ; Cell Differentiation ; Eosinophilia ; Eosinophils/physiology ; Histocompatibility Antigens Class II/immunology ; Immunoglobulin E/blood ; Immunoglobulin G/blood ; Interferon-gamma/genetics/metabolism ; Interleukins/genetics/metabolism ; Leukocyte Count ; Lymphocyte Activation ; Lymphoid Tissue/cytology/immunology ; *Membrane Proteins ; Mice ; Mice, Inbred BALB C ; Phenotype ; Phosphoproteins/*genetics/*physiology ; *Point Mutation ; Receptors, Antigen, T-Cell/analysis ; Signal Transduction ; T-Lymphocyte Subsets/immunology/physiology ; Th2 Cells/*immunology/physiology ; Thymus Gland/cytology/immunology
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  • 40
    Publication Date: 2002-09-07
    Description: The Golgi-localized, gamma-ear-containing, adenosine diphosphate ribosylation factor-binding proteins (GGAs) are multidomain proteins that bind mannose 6-phosphate receptors (MPRs) in the Golgi and have an essential role in lysosomal enzyme sorting. Here the GGAs and the coat protein adaptor protein-1 (AP-1) were shown to colocalize in clathrin-coated buds of the trans-Golgi networks of mouse L cells and human HeLa cells. Binding studies revealed a direct interaction between the hinge domains of the GGAs and the gamma-ear domain of AP-1. Further, AP-1 contained bound casein kinase-2 that phosphorylated GGA1 and GGA3, thereby causing autoinhibition. This could induce the directed transfer of the MPRs from GGAs to AP-1. MPRs that are defective in binding to GGAs are poorly incorporated into AP-1-containing clathrin-coated vesicles. Thus, the GGAs and AP-1 interact to package MPRs into AP-1-containing coated vesicles.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doray, Balraj -- Ghosh, Pradipta -- Griffith, Janice -- Geuze, Hans J -- Kornfeld, Stuart -- R01 CA-08759/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 6;297(5587):1700-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215646" target="_blank"〉PubMed〈/a〉
    Keywords: ADP-Ribosylation Factors/*metabolism ; Adaptor Proteins, Vesicular Transport ; Animals ; Biological Transport ; Carrier Proteins/*metabolism ; Cattle ; Cell Line ; Clathrin-Coated Vesicles/metabolism ; HeLa Cells ; Humans ; L Cells (Cell Line) ; Membrane Proteins/*metabolism ; Mice ; Mutation ; Phosphorylation ; Protein Binding ; Receptor, IGF Type 2/genetics/*metabolism ; Recombinant Proteins/metabolism ; trans-Golgi Network/*metabolism
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-07-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2002 Jul 19;297(5580):328.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12130764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Cell Count ; Cell Division ; Cells, Cultured ; Cerebral Cortex/cytology/*embryology ; Cytoskeletal Proteins/*genetics/physiology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/*genetics/physiology ; Humans ; Mice ; Mice, Transgenic ; Mutation ; Neurons/cytology/physiology ; Pituitary Gland/*cytology/growth & development ; Retina/*cytology/growth & development ; Stem Cells/cytology/*physiology ; Trans-Activators/*genetics/physiology ; beta Catenin
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  • 42
    Publication Date: 2002-09-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Snow, Melanie -- Cox, Shae-Lee -- Jenkin, Graham -- Trounson, Alan -- Shaw, Jillian -- New York, N.Y. -- Science. 2002 Sep 27;297(5590):2227.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Monash University, Victoria, Australia, 3800.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12351780" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryo Loss ; Embryo Transfer ; Embryonic and Fetal Development ; Female ; Fertility ; Fertilization in Vitro ; Gonadotropins, Equine/administration & dosage ; Male ; Mice ; Mice, Inbred Strains ; Mice, Nude ; Oocytes/*physiology ; Ovariectomy ; Ovary/*transplantation ; Pregnancy ; Pregnancy Outcome ; Rats ; *Reproductive Techniques, Assisted ; *Transplantation, Heterologous
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  • 43
    Publication Date: 2002-12-21
    Description: The immunoglobulin G (IgG)-containing B lymphocyte antigen receptor (IgG-BCR) transmits a signal distinct from that of IgM-BCR or IgD-BCR, although all three use the same signal-transducing component, Igalpha/Igbeta. Here we demonstrate that the inhibitory coreceptor CD22 down-modulates signaling through IgM-BCR and IgD-BCR, but not that through IgG-BCR, because of the IgG cytoplasmic tail, which prevents CD22 phosphorylation. These results suggest that the cytoplasmic tail of IgG specifically enhances IgG-BCR signaling by preventing CD22-mediated signal inhibition. Enhanced signaling through IgG-BCR may be involved in efficient IgG production, which is crucial for immunity to pathogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakabayashi, Chisato -- Adachi, Takahiro -- Wienands, Jurgen -- Tsubata, Takeshi -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2392-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12493916" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, B-Lymphocyte/metabolism ; B-Lymphocytes/immunology/metabolism ; Calcium/metabolism ; Calcium Signaling ; *Cell Adhesion Molecules ; Cells, Cultured ; Immunoglobulin D/immunology/metabolism ; Immunoglobulin G/chemistry/immunology/*metabolism ; Intracellular Signaling Peptides and Proteins ; Lectins/metabolism ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 ; Protein Tyrosine Phosphatases/metabolism ; Receptors, Antigen, B-Cell/chemistry/immunology/*metabolism ; Sialic Acid Binding Ig-like Lectin 2 ; *Signal Transduction ; Transfection ; Tumor Cells, Cultured
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  • 44
    Publication Date: 2002-05-23
    Description: Lymphocyte motility is vital for trafficking within lymphoid organs and for initiating contact with antigen-presenting cells. Visualization of these processes has previously been limited to in vitro systems. We describe the use of two-photon laser microscopy to image the dynamic behavior of individual living lymphocytes deep within intact lymph nodes. In their native environment, T cells achieved peak velocities of more than 25 micrometers per minute, displaying a motility coefficient that is five to six times that of B cells. Antigenic challenge changed T cell trajectories from random walks to "swarms" and stable clusters. Real-time two-photon imaging reveals lymphocyte behaviors that are fundamental to the initiation of the immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Mark J -- Wei, Sindy H -- Parker, Ian -- Cahalan, Michael D -- GM-41514/GM/NIGMS NIH HHS/ -- GM-48071/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 7;296(5574):1869-73. Epub 2002 May 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of California, Irvine, CA 92697-4561, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12016203" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigen-Presenting Cells/immunology/physiology ; Antigens/*immunology ; B-Lymphocytes/cytology/immunology/physiology ; Cell Division ; Cell Movement ; Cell Size ; Fluoresceins ; Fluorescent Dyes ; Image Processing, Computer-Assisted ; Lasers ; Lymph Nodes/cytology/*immunology ; *Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Microscopy/methods ; Motion Pictures as Topic ; Photons ; Rhodamines ; Succinimides ; T-Lymphocytes/cytology/immunology/*physiology ; Temperature
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-05-04
    Description: Neurons seem to have at least two self-destruct programs. Like other cell types, they have an intracellular death program for undergoing apoptosis when they are injured, infected, or not needed. In addition, they apparently have a second, molecularly distinct self-destruct program in their axon. This program is activated when the axon is severed and leads to the rapid degeneration of the isolated part of the cut axon. Do neurons also use this second program to prune their axonal tree during development and to conserve resources in response to chronic insults?〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Raff, Martin C -- Whitmore, Alan V -- Finn, John T -- New York, N.Y. -- Science. 2002 May 3;296(5569):868-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory for Molecular Cell Biology and Cell Biology Unit and the Biology Department, University College London, London WC1E 6BT, UK. m.raff@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Axons/*physiology ; Humans ; Mice ; Mice, Mutant Strains ; Motor Neuron Disease/pathology/physiopathology ; *Nerve Degeneration ; Neurodegenerative Diseases/pathology/*physiopathology ; Peripheral Nervous System Diseases/pathology/physiopathology ; *Wallerian Degeneration/genetics
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-03-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, Gretchen -- New York, N.Y. -- Science. 2002 Mar 15;295(5562):1989-91.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11896242" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; *Cell Differentiation ; *Cell Fusion ; Cell Lineage ; Cells, Cultured ; Chromosome Aberrations ; Embryo, Mammalian/cytology ; Hybrid Cells/*physiology ; Mice ; Polyploidy ; Stem Cells/cytology/*physiology
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  • 47
    Publication Date: 2002-04-16
    Description: Although humans and their closest evolutionary relatives, the chimpanzees, are 98.7% identical in their genomic DNA sequences, they differ in many morphological, behavioral, and cognitive aspects. The underlying genetic basis of many of these differences may be altered gene expression. We have compared the transcriptome in blood leukocytes, liver, and brain of humans, chimpanzees, orangutans, and macaques using microarrays, as well as protein expression patterns of humans and chimpanzees using two-dimensional gel electrophoresis. We also studied three mouse species that are approximately as related to each other as are humans, chimpanzees, and orangutans. We identified species-specific gene expression patterns indicating that changes in protein and gene expression have been particularly pronounced in the human brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Enard, Wolfgang -- Khaitovich, Philipp -- Klose, Joachim -- Zollner, Sebastian -- Heissig, Florian -- Giavalisco, Patrick -- Nieselt-Struwe, Kay -- Muchmore, Elaine -- Varki, Ajit -- Ravid, Rivka -- Doxiadis, Gaby M -- Bontrop, Ronald E -- Paabo, Svante -- New York, N.Y. -- Science. 2002 Apr 12;296(5566):340-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max-Planck-Institute for Evolutionary Anthropology, Inselstrasse 22, D-04103 Leipzig, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11951044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; Brain/*metabolism ; DNA, Complementary ; Female ; *Gene Expression ; Gene Expression Profiling ; Haplorhini/*genetics ; Hominidae/genetics ; Humans ; Leukocytes/*metabolism ; Liver/*metabolism ; Macaca mulatta/genetics ; Male ; Mice ; Muridae/genetics ; Oligonucleotide Array Sequence Analysis ; Organ Specificity ; Pan troglodytes/genetics ; Pongo pygmaeus/genetics ; Proteins/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Species Specificity
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  • 48
    Publication Date: 2002-11-02
    Description: Inactivation of the murine TATA binding protein (TBP) gene by homologous recombination leads to growth arrest and apoptosis at the embryonic blastocyst stage. However, after loss of TBP, RNA polymerase II (pol II) remains in a transcriptionally active phosphorylation state, and in situ run-on experiments showed high levels of pol II transcription comparable to those of wild-type cells. In contrast, pol I and pol III transcription was arrested. Our results show a differential dependency of the RNA polymerases on TBP and provide evidence for TBP-independent pol II transcriptional mechanisms that allow reinitiation and maintenance of gene transcription in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martianov, Igor -- Viville, Stephane -- Davidson, Irwin -- New York, N.Y. -- Science. 2002 Nov 1;298(5595):1036-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS/INSERM/ULP, B.P. 163, 67404 Illkirch Cedex, Communaute Urbaine de Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12411709" target="_blank"〉PubMed〈/a〉
    Keywords: Amanitins/pharmacology ; Animals ; Apoptosis ; Blastocyst/metabolism ; Cell Division ; Cell Nucleolus/metabolism ; Crosses, Genetic ; Embryonic and Fetal Development ; Female ; Gene Silencing ; Gene Targeting ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Phenotype ; RNA Polymerase I/metabolism ; RNA Polymerase II/*metabolism ; RNA Polymerase III/metabolism ; Recombination, Genetic ; TATA-Box Binding Protein/genetics/*physiology ; *Transcription, Genetic
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  • 49
    Publication Date: 2002-04-16
    Description: Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid metabolism and electron transport, and reduced susceptibility to fatigue during repetitive contractions. CaMK induced expression of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), a master regulator of mitochondrial biogenesis in vivo, and activated the PGC-1 gene promoter in cultured myocytes. Thus, a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Hai -- Kanatous, Shane B -- Thurmond, Frederick A -- Gallardo, Teresa -- Isotani, Eiji -- Bassel-Duby, Rhonda -- Williams, R Sanders -- AR40849/AR/NIAMS NIH HHS/ -- HL06296/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Apr 12;296(5566):349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11951046" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 4 ; Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism ; DNA Replication ; DNA, Mitochondrial/biosynthesis ; Electron Transport ; Fatty Acids/metabolism ; Gene Expression ; Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitochondria, Muscle/enzymology/*metabolism ; Muscle Contraction ; Muscle Fatigue ; Muscle Fibers, Skeletal/ultrastructure ; Muscle, Skeletal/enzymology/*metabolism/ultrastructure ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Signal Transduction ; Transcription Factors/genetics/metabolism ; Transgenes ; Up-Regulation
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  • 50
    Publication Date: 2002-02-02
    Description: The hypoxia-inducible factors (HIFs) 1alpha and 2alpha are key mammalian transcription factors that exhibit dramatic increases in both protein stability and intrinsic transcriptional potency during low-oxygen stress. This increased stability is due to the absence of proline hydroxylation, which in normoxia promotes binding of HIF to the von Hippel-Lindau (VHL tumor suppressor) ubiquitin ligase. We now show that hypoxic induction of the COOH-terminal transactivation domain (CAD) of HIF occurs through abrogation of hydroxylation of a conserved asparagine in the CAD. Inhibitors of Fe(II)- and 2-oxoglutarate-dependent dioxygenases prevented hydroxylation of the Asn, thus allowing the CAD to interact with the p300 transcription coactivator. Replacement of the conserved Asn by Ala resulted in constitutive p300 interaction and strong transcriptional activity. Full induction of HIF-1alpha and -2alpha, therefore, relies on the abrogation of both Pro and Asn hydroxylation, which during normoxia occur at the degradation and COOH-terminal transactivation domains, respectively.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lando, David -- Peet, Daniel J -- Whelan, Dean A -- Gorman, Jeffrey J -- Whitelaw, Murray L -- New York, N.Y. -- Science. 2002 Feb 1;295(5556):858-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biosciences (Biochemistry), Adelaide University, SA 5005, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823643" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Asparagine/*metabolism ; Basic Helix-Loop-Helix Transcription Factors ; Cell Hypoxia/*physiology ; Cell Line ; Humans ; Hydroxylation ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mass Spectrometry ; Mice ; Mixed Function Oxygenases/metabolism ; Molecular Sequence Data ; Mutation ; Oxygen/*physiology ; Proline/metabolism ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/chemistry/genetics/*metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; *Transcriptional Activation
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  • 51
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gershenwald, Jeffrey E -- Fidler, Isaiah J -- New York, N.Y. -- Science. 2002 Jun 7;296(5574):1811-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12052939" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endothelial Growth Factors/antagonists & inhibitors/*metabolism ; Fibrosarcoma/metabolism/*pathology/physiopathology/secondary ; Humans ; *Lymphatic Metastasis/prevention & control ; Lymphatic System/*pathology/physiology ; Lymphedema/chemically induced ; Melanoma, Experimental/metabolism/*pathology/physiopathology/secondary ; Mice ; Neoplasms/pathology ; Vascular Endothelial Growth Factor C
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  • 52
    Publication Date: 2002-01-12
    Description: T-bet is a member of the T-box family of transcription factors that appears to regulate lineage commitment in CD4 T helper (TH) lymphocytes in part by activating the hallmark TH1 cytokine, interferon-gamma (IFN-gamma). IFN-gamma is also produced by natural killer (NK) cells and most prominently by CD8 cytotoxic T cells, and is vital for the control of microbial pathogens. Although T-bet is expressed in all these cell types, it is required for control of IFN-gamma production in CD4 and NK cells, but not in CD8 cells. This difference is also apparent in the function of these cell subsets. Thus, the regulation of a single cytokine, IFN-gamma, is controlled by distinct transcriptional mechanisms within the T cell lineage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Szabo, Susanne J -- Sullivan, Brandon M -- Stemmann, Claudia -- Satoskar, Abhay R -- Sleckman, Barry P -- Glimcher, Laurie H -- New York, N.Y. -- Science. 2002 Jan 11;295(5553):338-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11786644" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD4-Positive T-Lymphocytes/*immunology/physiology ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cytotoxicity, Immunologic ; Gene Targeting ; Immunization ; Immunoglobulin G/biosynthesis ; Interferon-gamma/*biosynthesis ; Interleukin-4/biosynthesis ; Interleukin-5/biosynthesis ; Killer Cells, Natural/immunology/metabolism ; Leishmania major ; Leishmaniasis, Cutaneous/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Box Domain Proteins ; T-Lymphocytes, Cytotoxic/*immunology ; Th1 Cells/*immunology ; Transcription Factors/deficiency/*genetics/*physiology
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-01-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghosh, Anirvan -- New York, N.Y. -- Science. 2002 Jan 18;295(5554):449-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. aghosh@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11799227" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Ephrin-B2 ; Glutamic Acid/metabolism ; Hippocampus/metabolism/physiology ; Ligands ; Membrane Proteins/*metabolism/pharmacology ; Mice ; *Neuronal Plasticity ; Neurons/metabolism/physiology ; Phosphorylation ; Protein Structure, Tertiary ; Receptor Protein-Tyrosine Kinases/chemistry/genetics/*metabolism ; Receptor, EphB4 ; Receptors, Eph Family ; Receptors, N-Methyl-D-Aspartate/chemistry/*metabolism ; Signal Transduction ; Synapses/*metabolism ; Synaptic Membranes/metabolism ; src-Family Kinases/metabolism
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  • 54
    Publication Date: 2002-08-24
    Description: Insulin secretion from intact mouse pancreatic islets was investigated with two-photon excitation imaging. Insulin granule exocytosis occurred mainly toward the interstitial space, away from blood vessels. The fusion pore was unusually stable with a lifetime of 1.8 seconds. Opening of the 1.4-nanometer-diameter pore was preceded by unrestricted lateral diffusion of lipids along the inner wall of the pore, supporting the idea that this structure is composed of membrane lipids. When the pore dilated to 12 nanometers, the granules rapidly flattened and discharged their contents. Thus, our methodology reveals fusion pore dynamics in intact tissues at nanometer resolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takahashi, Noriko -- Kishimoto, Takuya -- Nemoto, Tomomi -- Kadowaki, Takashi -- Kasai, Haruo -- New York, N.Y. -- Science. 2002 Aug 23;297(5585):1349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Physiology, National Institute for Physiological Sciences, and the Graduate University of Advanced Studies, Myodaiji, Okazaki 444-8585, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193788" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/physiology/*ultrastructure ; Cell Polarity ; Colforsin/pharmacology ; Diffusion ; *Exocytosis ; Extracellular Space ; Fluorescence ; Glucose/pharmacology ; Guinea Pigs ; Image Processing, Computer-Assisted ; Insulin/*secretion ; Intracellular Membranes/physiology/ultrastructure ; Islets of Langerhans/blood supply/*physiology/secretion/*ultrastructure ; Kinetics ; Membrane Fusion ; Membrane Lipids/physiology ; Mice ; Mice, Inbred ICR ; Permeability ; Pyridinium Compounds ; Quaternary Ammonium Compounds ; Rhodamines ; Secretory Vesicles/physiology/*ultrastructure
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  • 55
    Publication Date: 2002-07-13
    Description: Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. N-methyl-N'-nitro-N-nitrosoguanidine, H2O2, and N-methyl-d-aspartate induce AIF translocation and cell death, which is prevented by PARP inhibitors or genetic knockout of PARP-1, but is caspase independent. Microinjection of an antibody to AIF protects against PARP-1-dependent cytotoxicity. These data support a model in which PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent pathway of programmed cell death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Seong-Woon -- Wang, Hongmin -- Poitras, Marc F -- Coombs, Carmen -- Bowers, William J -- Federoff, Howard J -- Poirier, Guy G -- Dawson, Ted M -- Dawson, Valina L -- New York, N.Y. -- Science. 2002 Jul 12;297(5579):259-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12114629" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Animals ; Antibodies/immunology ; *Apoptosis ; Apoptosis Inducing Factor ; Caspase Inhibitors ; Caspases/metabolism ; Cell Nucleus/metabolism ; Cells, Cultured ; Cytochrome c Group/metabolism ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Flavoproteins/immunology/*metabolism ; Hydrogen Peroxide/pharmacology ; Membrane Potentials ; Membrane Proteins/immunology/*metabolism ; Methylnitronitrosoguanidine/pharmacology ; Mice ; Mice, Knockout ; Mitochondria/metabolism/physiology ; N-Methylaspartate/metabolism/pharmacology ; NAD/metabolism ; Neurons/cytology/physiology ; Oxidative Stress ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/genetics/*metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-12-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, Ian C -- Stainier, Didier Y R -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2141-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA. ianjr88@itsa.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481123" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bromodeoxyuridine/metabolism ; *Cell Cycle Proteins ; Cell Differentiation ; *Cell Division ; Extremities/physiology ; Heart/*physiology ; Heart Injuries/pathology/physiopathology ; Heart Ventricles/surgery ; Humans ; Mice ; Mutation ; Myocytes, Cardiac/*physiology ; *Protein Kinases ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Protein-Tyrosine Kinases/genetics/metabolism ; *Regeneration/genetics/physiology ; Zebrafish/genetics/*physiology ; *Zebrafish Proteins
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  • 57
    Publication Date: 2002-12-14
    Description: The master circadian oscillator in the hypothalamic suprachiasmatic nucleus is entrained to the day/night cycle by retinal photoreceptors. Melanopsin (Opn4), an opsin-based photopigment, is a primary candidate for photoreceptor-mediated entrainment. To investigate the functional role of melanopsin in light resetting of the oscillator, we generated melanopsin-null mice (Opn4-/-). These mice entrain to a light/dark cycle and do not exhibit any overt defect in circadian activity rhythms under constant darkness. However, they display severely attenuated phase resetting in response to brief pulses of monochromatic light, highlighting the critical role of melanopsin in circadian photoentrainment in mammals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Panda, Satchidananda -- Sato, Trey K -- Castrucci, Ana Maria -- Rollag, Mark D -- DeGrip, Willem J -- Hogenesch, John B -- Provencio, Ignacio -- Kay, Steve A -- MH 62405/MH/NIMH NIH HHS/ -- MH51573/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 13;298(5601):2213-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12481141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/physiology ; Circadian Rhythm/*physiology ; Darkness ; Female ; Gene Targeting ; *Light ; Light Signal Transduction ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; Retinal Ganglion Cells/physiology ; Rod Opsins/genetics/*physiology ; Suprachiasmatic Nucleus/physiology
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-12-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boehning, Darren -- Snyder, Solomon H -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2339-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12493901" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Autonomic Nervous System/metabolism ; Basic Helix-Loop-Helix Transcription Factors ; Behavior, Animal ; Brain/metabolism ; CLOCK Proteins ; Carbon Monoxide/*metabolism/pharmacology ; *Circadian Rhythm/genetics ; DNA/metabolism ; Diffusion ; Dimerization ; Helix-Loop-Helix Motifs ; Heme/metabolism ; Heme Oxygenase (Decyclizing)/metabolism ; Mice ; Models, Genetic ; NAD/metabolism ; NADP/metabolism ; Nerve Tissue Proteins/*chemistry/*metabolism ; Neurons/*metabolism ; Neurotransmitter Agents/metabolism ; Oxidation-Reduction ; Protein Structure, Tertiary ; Synaptic Transmission ; Trans-Activators/metabolism ; Transcription Factors/*chemistry/*metabolism ; Transcription, Genetic
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  • 59
    Publication Date: 2002-02-23
    Description: The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamination by genetic analysis of the roles of the class III POU domain transcription factors, Brn-1 and Brn-2, expressed during the development of the forebrain and coexpressed in most layer II-V cortical neurons. Brn-1 and Brn-2 appear to critically control the initiation of radial migration, redundantly regulating the cell-autonomous expression of the p35 and p39 regulatory subunits of Cdk5 in migrating cortical neurons, with Brn-1(-/-)/Brn-2(-/-) mice exhibiting cortical inversion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McEvilly, Robert J -- de Diaz, Marcela Ortiz -- Schonemann, Marcus D -- Hooshmand, Farideh -- Rosenfeld, Michael G -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1528-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0648, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11859196" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/cytology/embryology/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; Cell Line ; Cell Movement ; Cerebral Cortex/cytology/embryology/*metabolism ; Cyclin-Dependent Kinase 5 ; Cyclin-Dependent Kinases/metabolism ; Extracellular Matrix Proteins/genetics/metabolism ; Female ; Gene Targeting ; Hippocampus/cytology/embryology/metabolism ; Homeodomain Proteins ; In Situ Hybridization ; Male ; Mice ; Mutation ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/*physiology ; Neuropeptides/genetics/*physiology ; POU Domain Factors ; Serine Endopeptidases ; Trans-Activators/genetics/*physiology ; Transcription Factors/genetics/*physiology ; *Transcription, Genetic
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  • 60
    Publication Date: 2002-09-07
    Description: Distal limb development and specification of digit identities in tetrapods are under the control of a mesenchymal organizer called the polarizing region. Sonic Hedgehog (SHH) is the morphogenetic signal produced by the polarizing region in the posterior limb bud. Ectopic anterior SHH signaling induces digit duplications and has been suspected as a major cause underlying congenital malformations that result in digit polydactyly. Here, we report that the polydactyly of Gli3-deficient mice arises independently of SHH signaling. Disruption of one or both Gli3 alleles in mouse embryos lacking Shh progressively restores limb distal development and digit formation. Our genetic analysis indicates that SHH signaling counteracts GLI3-mediated repression of key regulator genes, cell survival, and distal progression of limb bud development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉te Welscher, Pascal -- Zuniga, Aimee -- Kuijper, Sanne -- Drenth, Thijs -- Goedemans, Hans J -- Meijlink, Frits -- Zeller, Rolf -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):827-30. Epub 2002 Sep 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Faculty of Biology, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215652" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors ; Cell Death ; DNA-Binding Proteins/genetics/*physiology ; Extremities/*embryology ; Fibroblast Growth Factors/genetics/metabolism ; Gene Expression Regulation, Developmental ; Genes, Homeobox ; Hedgehog Proteins ; Homeodomain Proteins/genetics/metabolism ; *Intercellular Signaling Peptides and Proteins ; Kruppel-Like Transcription Factors ; Limb Buds/cytology/embryology/metabolism ; Membrane Proteins/genetics/metabolism ; Mice ; Mutation ; *Nerve Tissue Proteins ; Oncogene Proteins/genetics/metabolism ; Polydactyly/genetics ; Proteins/genetics/physiology ; Receptors, Cell Surface ; Signal Transduction ; Trans-Activators/genetics/*physiology ; Transcription Factors/genetics/metabolism/*physiology ; Zebrafish Proteins
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  • 61
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-11-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ting, Alice Y -- Endy, Drew -- New York, N.Y. -- Science. 2002 Nov 8;298(5596):1189-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12424362" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Nucleus/metabolism ; Chemokine CCL5/genetics ; Chemokine CXCL10 ; Chemokines, CXC/genetics ; Computer Simulation ; Cytoplasm/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Feedback, Physiological ; *Gene Expression Regulation ; Humans ; I-kappa B Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Models, Biological ; NF-kappa B/*metabolism ; Proto-Oncogene Proteins/genetics/metabolism ; *Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism/pharmacology
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-09-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gura, Trisha -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):1982-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242421" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Animals ; *Biotechnology/economics ; Chemistry, Pharmaceutical ; Clinical Trials as Topic ; Computational Biology ; Databases, Genetic ; Disease Models, Animal ; *Drug Design ; *Drug Industry/economics ; *Genomics/economics ; Humans ; Investments ; Mice ; *Pharmaceutical Preparations ; Private Sector ; Public Sector
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  • 63
    Publication Date: 2002-07-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Browder, Timothy -- Folkman, Judah -- Hahnfeldt, Philip -- Heymach, John -- Hlatky, Lynn -- Kieran, Mark -- Rogers, Michael S -- New York, N.Y. -- Science. 2002 Jul 26;297(5581):471; discussion 471.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12143876" target="_blank"〉PubMed〈/a〉
    Keywords: Angiogenesis Inhibitors/*therapeutic use ; Animals ; *Genes, p53 ; Growth Substances/metabolism ; Humans ; Mice ; Neoplasms, Experimental/blood supply/*drug therapy/genetics/pathology ; Neovascularization, Pathologic ; Receptor Protein-Tyrosine Kinases/immunology/metabolism ; Receptors, Growth Factor/immunology/metabolism ; Receptors, Vascular Endothelial Growth Factor ; Tumor Cells, Cultured
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-04-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vane, John R -- New York, N.Y. -- Science. 2002 Apr 19;296(5567):474-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London EC1M 6BQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11964462" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Carotid Artery Injuries/pathology ; Cell Division ; Clinical Trials as Topic ; Cyclooxygenase 1 ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/*adverse effects/pharmacology/therapeutic use ; Epoprostenol/*metabolism ; Homeostasis ; Humans ; Isoenzymes/antagonists & inhibitors ; Lactones/*adverse effects/pharmacology/therapeutic use ; Membrane Proteins ; Mice ; Muscle, Smooth, Vascular/cytology ; Myocardial Infarction/epidemiology ; Naproxen/therapeutic use ; Platelet Activation/*drug effects ; Prostaglandin-Endoperoxide Synthases ; Receptors, Epoprostenol ; Receptors, Prostaglandin/genetics/metabolism ; Receptors, Thromboxane/genetics/metabolism ; Sulfones ; Thromboxane A2/*metabolism
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  • 65
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-03-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karre, Klas -- New York, N.Y. -- Science. 2002 Mar 15;295(5562):2029-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11896262" target="_blank"〉PubMed〈/a〉
    Keywords: Acute Disease ; Animals ; *Antigens, Ly ; Graft vs Host Disease/immunology ; Graft vs Leukemia Effect/immunology ; H-2 Antigens/immunology ; HLA Antigens/*immunology ; *Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; Host vs Graft Reaction/immunology ; Humans ; Killer Cells, Natural/*immunology/transplantation ; Lectins, C-Type ; Leukemia/immunology/*therapy ; Leukemia, Myeloid/immunology/*therapy ; Ligands ; Membrane Glycoproteins/metabolism ; Mice ; Receptors, Immunologic/metabolism ; Receptors, KIR ; Receptors, NK Cell Lectin-Like ; Transplantation Conditioning
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  • 66
    Publication Date: 2002-03-02
    Description: The gastrointestinal tract is lined by a layer of mucus comprised of highly glycosylated proteins called mucins. To evaluate the importance of mucin in intestinal carcinogenesis, we constructed mice genetically deficient in Muc2, the most abundant secreted gastrointestinal mucin. Muc2-/- mice displayed aberrant intestinal crypt morphology and altered cell maturation and migration. Most notably, the mice frequently developed adenomas in the small intestine that progressed to invasive adenocarcinoma, as well as rectal tumors. Thus, Muc2 is involved in the suppression of colorectal cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Velcich, Anna -- Yang, WanCai -- Heyer, Joerg -- Fragale, Alessandra -- Nicholas, Courtney -- Viani, Stephanie -- Kucherlapati, Raju -- Lipkin, Martin -- Yang, Kan -- Augenlicht, Leonard -- CA 72835/CA/NCI NIH HHS/ -- CA 90808/CA/NCI NIH HHS/ -- P0 CA 13330/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 1;295(5560):1726-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, 111 East 210 Street, Bronx, NY 10467, USA. velcich@aecom.yu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11872843" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/chemistry/pathology ; Adenoma/chemistry/pathology ; Animals ; Apoptosis ; Cell Differentiation ; Cell Division ; Cell Lineage ; Cell Movement ; Colon/chemistry/cytology/pathology ; Colorectal Neoplasms/*etiology/metabolism/pathology ; Cytoskeletal Proteins/analysis ; Disease Progression ; Duodenal Neoplasms/chemistry/pathology ; Duodenum/chemistry/cytology/pathology ; Epithelial Cells/chemistry/physiology ; Female ; Gene Targeting ; Goblet Cells/cytology ; Intestinal Mucosa/chemistry/cytology/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mucin-2 ; Mucins/analysis/*genetics/*physiology ; Proto-Oncogene Proteins c-myc/analysis ; *Trans-Activators ; beta Catenin
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  • 67
    Publication Date: 2002-01-19
    Description: To explore neuronal mechanisms underlying long-term consequences of stress, we studied stress-induced changes in the neuritic translocation of acetylcholinesterase (AChE) splice variants. Under normal conditions, we found the synaptic AChE-S mRNA and protein in neurites. Corticosterone, anticholinesterases, and forced swim, each facilitated a rapid (minutes), yet long-lasting (weeks), shift from AChE-S to the normally rare AChE-R mRNA, promoted AChE-R mRNA translocation into neurites, and induced enzyme secretion. Weeks after stress, electrophysiological measurements in hippocampus slices displayed apparently normal evoked synaptic responses but extreme hypersensitivity to both anticholinesterases and atropine. Our findings suggest that neuronal hypersensitivity under stress involves neuritic replacement of AChE-S with AChE-R.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meshorer, Eran -- Erb, Christina -- Gazit, Roi -- Pavlovsky, Lev -- Kaufer, Daniela -- Friedman, Alon -- Glick, David -- Ben-Arie, Nissim -- Soreq, Hermona -- New York, N.Y. -- Science. 2002 Jan 18;295(5554):508-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, The Institute of Life Sciences and The Eric Roland Center for Neurodegenerative Diseases, The Hebrew University of Jerusalem, Israel 91904.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11799248" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Acetylcholinesterase/*genetics/*metabolism ; Action Potentials ; *Alternative Splicing ; Animals ; Atropine/pharmacology ; Cells, Cultured ; Cerebellum/cytology ; Cholinesterase Inhibitors/pharmacology ; Corticosterone/pharmacology ; Hippocampus/cytology/metabolism/physiology ; In Situ Hybridization, Fluorescence ; In Vitro Techniques ; Mice ; Mice, Transgenic ; Neurites/*metabolism ; Neurons/*metabolism ; Oligonucleotides, Antisense/pharmacology ; PC12 Cells ; Physostigmine/pharmacology ; RNA, Messenger/genetics/*metabolism ; Rats ; Stress, Physiological/genetics/*physiopathology ; Time Factors
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  • 68
    Publication Date: 2002-06-08
    Description: Analysis of recombination between loci (linkage analysis) has been a cornerstone of human genetic research, enabling investigators to localize and, ultimately, identify genetic loci. However, despite these efforts little is known about patterns of meiotic exchange in human germ cells or the mechanisms that control these patterns. Using recently developed immunofluorescence methodology to examine exchanges in human spermatocytes, we have identified remarkable variation in the rate of recombination within and among individuals. Subsequent analyses indicate that, in humans and mice, this variation is linked to differences in the length of the synaptonemal complex. Thus, at least in mammals, a physical structure, the synaptonemal complex, reflects genetic rather than physical distance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lynn, Audrey -- Koehler, Kara E -- Judis, LuAnn -- Chan, Ernest R -- Cherry, Jonathan P -- Schwartz, Stuart -- Seftel, Allen -- Hunt, Patricia A -- Hassold, Terry J -- HD07518/HD/NICHD NIH HHS/ -- HD21341/HD/NICHD NIH HHS/ -- HD37502/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2222-5. Epub 2002 Jun 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Case Western Reserve University, Cleveland, OH, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12052900" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Animals ; Carrier Proteins ; Chromosomes, Human/physiology/*ultrastructure ; Crossing Over, Genetic ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; *Meiosis ; Mice ; Mice, Inbred Strains ; Microscopy, Fluorescence ; Middle Aged ; Neoplasm Proteins/analysis ; Nuclear Proteins ; *Recombination, Genetic ; Spermatocytes/physiology/*ultrastructure ; Synaptonemal Complex/*ultrastructure
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉von Andrian, Ulrich H -- New York, N.Y. -- Science. 2002 Jun 7;296(5574):1815-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. uva@cbr.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12052942" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigen Presentation ; Antigens/immunology ; Cell Movement ; Dendritic Cells/*immunology/physiology ; Lasers ; Lymph Nodes/*immunology ; *Lymphocyte Activation ; Mice ; Microscopy/methods ; Microscopy, Confocal/methods ; Microscopy, Fluorescence ; Organ Culture Techniques ; Ovalbumin/immunology ; Oxygen/physiology ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/cytology/*immunology/physiology ; T-Lymphocytes, Helper-Inducer/immunology/physiology ; Thymus Gland/cytology/immunology
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-11-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hempstead, Barbara L -- Salzer, James L -- New York, N.Y. -- Science. 2002 Nov 8;298(5596):1184-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. blhempst@med.Cornell.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12424359" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Brain-Derived Neurotrophic Factor/pharmacology/*physiology ; Central Nervous System/physiology ; Ligands ; Mice ; Models, Neurological ; Myelin Sheath/*physiology ; Nerve Regeneration ; Neurotrophin 3/pharmacology/*physiology ; Oligodendroglia/physiology ; Paracrine Communication ; Peripheral Nervous System/physiology ; Receptor, Nerve Growth Factor ; Receptor, trkC/*physiology ; Receptors, Nerve Growth Factor/*physiology ; Schwann Cells/*physiology ; Signal Transduction
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2002 Jun 21;296(5576):2121-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12077377" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arteries/*embryology ; Axons/physiology ; Body Patterning ; Endothelial Growth Factors/pharmacology/*physiology ; Humans ; Lymphokines/pharmacology/*physiology ; Mice ; Mobius Syndrome/pathology ; Morphogenesis ; Mutation ; Peripheral Nervous System/*embryology/metabolism ; Skin/blood supply/embryology/innervation ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
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  • 72
    Publication Date: 2002-06-29
    Description: Myeloperoxidase (MPO) is an abundant mammalian phagocyte hemoprotein thought to primarily mediate host defense reactions. Although its microbicidal functions are well established in vitro, humans deficient in MPO are not at unusual risk of infection. MPO was observed herein to modulate the vascular signaling and vasodilatory functions of nitric oxide (NO) during acute inflammation. After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant. Altered vascular responsiveness was due to catalytic consumption of NO by substrate radicals generated by MPO. Thus MPO can directly modulate vascular inflammatory responses by regulating NO bioavailability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eiserich, Jason P -- Baldus, Stephan -- Brennan, Marie-Luise -- Ma, Wenxin -- Zhang, Chunxiang -- Tousson, Albert -- Castro, Laura -- Lusis, Aldons J -- Nauseef, William M -- White, C Roger -- Freeman, Bruce A -- I01 BX000513/BX/BLRD VA/ -- R01 HL067930/HL/NHLBI NIH HHS/ -- R03 TW005682/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Jun 28;296(5577):2391-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Division of Nephrology, University of California, Davis, CA 95616, USA. jpeiserich@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12089442" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta ; Catalysis ; Cattle ; Cells, Cultured ; Chromans/metabolism/pharmacology ; Coculture Techniques ; Cyclic GMP/metabolism ; Endothelium, Vascular/enzymology/*physiology ; Endotoxemia/enzymology ; Humans ; Hydrogen Peroxide/metabolism/pharmacology ; Inflammation/*enzymology/physiopathology ; Leukocytes/*enzymology ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular/metabolism ; Mutation ; Nitric Oxide/*metabolism ; Oxidation-Reduction ; Peroxidase/genetics/*metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transfection ; Tumor Cells, Cultured ; *Vasodilation
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  • 73
    Publication Date: 2002-07-27
    Description: Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570540/" 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/PMC2570540/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mahdavi, Jafar -- Sonden, Berit -- Hurtig, Marina -- Olfat, Farzad O -- Forsberg, Lina -- Roche, Niamh -- Angstrom, Jonas -- Larsson, Thomas -- Teneberg, Susann -- Karlsson, Karl-Anders -- Altraja, Siiri -- Wadstrom, Torkel -- Kersulyte, Dangeruta -- Berg, Douglas E -- Dubois, Andre -- Petersson, Christoffer -- Magnusson, Karl-Eric -- Norberg, Thomas -- Lindh, Frank -- Lundskog, Bertil B -- Arnqvist, Anna -- Hammarstrom, Lennart -- Boren, Thomas -- P30 DK52574/DK/NIDDK NIH HHS/ -- R01 AI38166/AI/NIAID NIH HHS/ -- R01 CA082312/CA/NCI NIH HHS/ -- R01 CA082312-08/CA/NCI NIH HHS/ -- R01 DK53727/DK/NIDDK NIH HHS/ -- R03 AI49161/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 26;297(5581):573-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Odontology/Oral Microbiology, Umea University, SE-901 87 Umea, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12142529" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Bacterial/chemistry/genetics/isolation & purification/*metabolism ; Amino Acid Sequence ; Animals ; Antigens, CD15/*metabolism ; *Bacterial Adhesion ; Carbohydrate Sequence ; Carrier Proteins/genetics/metabolism ; Gastric Mucosa/immunology/metabolism/*microbiology ; Gastritis/immunology/metabolism/*microbiology ; Genes, Bacterial ; Glycoconjugates/metabolism ; Helicobacter Infections/immunology/metabolism/*microbiology ; Helicobacter pylori/genetics/isolation & purification/*physiology ; Humans ; Macaca mulatta ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Oligosaccharides/*metabolism ; Sialic Acids/metabolism
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  • 74
    Publication Date: 2002-10-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chenn, Anjen -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):766-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611-3008, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12399574" target="_blank"〉PubMed〈/a〉
    Keywords: Adherens Junctions/physiology/ultrastructure ; Animals ; Apoptosis ; Awards and Prizes ; *Cell Cycle ; Cell Differentiation ; Cell Division ; Cerebral Cortex/anatomy & histology/*growth & development ; Cytoskeletal Proteins/*metabolism ; Humans ; Mice ; Mice, Transgenic ; Neurons/*cytology/physiology ; Signal Transduction ; Stem Cells/cytology/*physiology ; Trans-Activators/*metabolism ; beta Catenin
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  • 75
    Publication Date: 2002-06-18
    Description: Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T cells) exhibited an early block in T cell maturation but later developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma1 (PLC-gamma1) and of nuclear factor of activated T cells, calcium influx, interleukin-2 production, and cell death were reduced or abrogated in T cells from LAT mutant mice. In contrast, TCR-induced Erk activation was intact. These results identify a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T cell development and homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sommers, Connie L -- Park, Cheung-Seog -- Lee, Jan -- Feng, Chiguang -- Fuller, Claudette L -- Grinberg, Alexander -- Hildebrand, Jay A -- Lacana, Emanuela -- Menon, Rashmi K -- Shores, Elizabeth W -- Samelson, Lawrence E -- Love, Paul E -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2040-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12065840" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptor Proteins, Signal Transducing ; Animals ; Antibodies, Antinuclear/blood ; Antigens, CD5/analysis ; Autoimmune Diseases/immunology ; CD4-Positive T-Lymphocytes/immunology/physiology ; Calcium/metabolism ; Calcium Signaling ; Carrier Proteins/*genetics/*physiology ; Cell Division ; Interleukin-2/biosynthesis ; Isoenzymes/*metabolism ; Lymphocyte Activation ; Lymphoproliferative Disorders/*etiology/immunology/pathology ; MAP Kinase Signaling System ; *Membrane Proteins ; Mice ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinases/metabolism ; Phenotype ; Phospholipase C gamma ; Phosphoproteins/*genetics/*physiology ; Phosphorylation ; *Point Mutation ; Receptors, Antigen, T-Cell/immunology/metabolism ; Signal Transduction ; T-Lymphocyte Subsets/immunology/physiology ; T-Lymphocytes/*immunology/physiology ; Thymus Gland/cytology/immunology/pathology ; Transcription Factors/metabolism ; Type C Phospholipases/*metabolism ; ras Proteins/metabolism
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  • 76
    Publication Date: 2002-06-01
    Description: The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mural, Richard J -- Adams, Mark D -- Myers, Eugene W -- Smith, Hamilton O -- Miklos, George L Gabor -- Wides, Ron -- Halpern, Aaron -- Li, Peter W -- Sutton, Granger G -- Nadeau, Joe -- Salzberg, Steven L -- Holt, Robert A -- Kodira, Chinnappa D -- Lu, Fu -- Chen, Lin -- Deng, Zuoming -- Evangelista, Carlos C -- Gan, Weiniu -- Heiman, Thomas J -- Li, Jiayin -- Li, Zhenya -- Merkulov, Gennady V -- Milshina, Natalia V -- Naik, Ashwinikumar K -- Qi, Rong -- Shue, Bixiong Chris -- Wang, Aihui -- Wang, Jian -- Wang, Xin -- Yan, Xianghe -- Ye, Jane -- Yooseph, Shibu -- Zhao, Qi -- Zheng, Liansheng -- Zhu, Shiaoping C -- Biddick, Kendra -- Bolanos, Randall -- Delcher, Arthur L -- Dew, Ian M -- Fasulo, Daniel -- Flanigan, Michael J -- Huson, Daniel H -- Kravitz, Saul A -- Miller, Jason R -- Mobarry, Clark M -- Reinert, Knut -- Remington, Karin A -- Zhang, Qing -- Zheng, Xiangqun H -- Nusskern, Deborah R -- Lai, Zhongwu -- Lei, Yiding -- Zhong, Wenyan -- Yao, Alison -- Guan, Ping -- Ji, Rui-Ru -- Gu, Zhiping -- Wang, Zhen-Yuan -- Zhong, Fei -- Xiao, Chunlin -- Chiang, Chia-Chien -- Yandell, Mark -- Wortman, Jennifer R -- Amanatides, Peter G -- Hladun, Suzanne L -- Pratts, Eric C -- Johnson, Jeffery E -- Dodson, Kristina L -- Woodford, Kerry J -- Evans, Cheryl A -- Gropman, Barry -- Rusch, Douglas B -- Venter, Eli -- Wang, Mei -- Smith, Thomas J -- Houck, Jarrett T -- Tompkins, Donald E -- Haynes, Charles -- Jacob, Debbie -- Chin, Soo H -- Allen, David R -- Dahlke, Carl E -- Sanders, Robert -- Li, Kelvin -- Liu, Xiangjun -- Levitsky, Alexander A -- Majoros, William H -- Chen, Quan -- Xia, Ashley C -- Lopez, John R -- Donnelly, Michael T -- Newman, Matthew H -- Glodek, Anna -- Kraft, Cheryl L -- Nodell, Marc -- Ali, Feroze -- An, Hui-Jin -- Baldwin-Pitts, Danita -- Beeson, Karen Y -- Cai, Shuang -- Carnes, Mark -- Carver, Amy -- Caulk, Parris M -- Center, Angela -- Chen, Yen-Hui -- Cheng, Ming-Lai -- Coyne, My D -- Crowder, Michelle -- Danaher, Steven -- Davenport, Lionel B -- Desilets, Raymond -- Dietz, Susanne M -- Doup, Lisa -- Dullaghan, Patrick -- Ferriera, Steven -- Fosler, Carl R -- Gire, Harold C -- Gluecksmann, Andres -- Gocayne, Jeannine D -- Gray, Jonathan -- Hart, Brit -- Haynes, Jason -- Hoover, Jeffery -- Howland, Tim -- Ibegwam, Chinyere -- Jalali, Mena -- Johns, David -- Kline, Leslie -- Ma, Daniel S -- MacCawley, Steven -- Magoon, Anand -- Mann, Felecia -- May, David -- McIntosh, Tina C -- Mehta, Somil -- Moy, Linda -- Moy, Mee C -- Murphy, Brian J -- Murphy, Sean D -- Nelson, Keith A -- Nuri, Zubeda -- Parker, Kimberly A -- Prudhomme, Alexandre C -- Puri, Vinita N -- Qureshi, Hina -- Raley, John C -- Reardon, Matthew S -- Regier, Megan A -- Rogers, Yu-Hui C -- Romblad, Deanna L -- Schutz, Jakob -- Scott, John L -- Scott, Richard -- Sitter, Cynthia D -- Smallwood, Michella -- Sprague, Arlan C -- Stewart, Erin -- Strong, Renee V -- Suh, Ellen -- Sylvester, Karena -- Thomas, Reginald -- Tint, Ni Ni -- Tsonis, Christopher -- Wang, Gary -- Wang, George -- Williams, Monica S -- Williams, Sherita M -- Windsor, Sandra M -- Wolfe, Keriellen -- Wu, Mitchell M -- Zaveri, Jayshree -- Chaturvedi, Kabir -- Gabrielian, Andrei E -- Ke, Zhaoxi -- Sun, Jingtao -- Subramanian, Gangadharan -- Venter, J Craig -- Pfannkoch, Cynthia M -- Barnstead, Mary -- Stephenson, Lisa D -- New York, N.Y. -- Science. 2002 May 31;296(5573):1661-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. richard.mural@celera.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12040188" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Chromosomes/*genetics ; Chromosomes, Human/genetics ; Computational Biology ; Conserved Sequence ; Databases, Nucleic Acid ; Evolution, Molecular ; Genes ; Genetic Markers ; *Genome ; *Genome, Human ; Genomics ; Humans ; Mice ; Mice, Inbred A/genetics ; Mice, Inbred DBA/genetics ; Mice, Inbred Strains/*genetics ; Molecular Sequence Data ; Physical Chromosome Mapping ; Proteins/chemistry/genetics ; Sequence Alignment ; *Sequence Analysis, DNA ; Species Specificity ; *Synteny
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  • 77
    Publication Date: 2002-02-02
    Description: The mouse vomeronasal organ (VNO) is thought to mediate social behaviors and neuroendocrine changes elicited by pheromonal cues. The molecular mechanisms underlying the sensory response to pheromones and the behavioral repertoire induced through the VNO are not fully characterized. Using the tools of mouse genetics and multielectrode recording, we demonstrate that the sensory activation of VNO neurons requires TRP2, a putative ion channel of the transient receptor potential family that is expressed exclusively in these neurons. Moreover, we show that male mice deficient in TRP2 expression fail to display male-male aggression, and they initiate sexual and courtship behaviors toward both males and females. Our study suggests that, in the mouse, sensory activation of the VNO is essential for sex discrimination of conspecifics and thus ensures gender-specific behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stowers, Lisa -- Holy, Timothy E -- Meister, Markus -- Dulac, Catherine -- Koentges, Georgy -- DC03903/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1493-500. Epub 2002 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11823606" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Animals ; Chemoreceptor Cells/*physiology ; Crosses, Genetic ; Cues ; Electrophysiology ; Electroporation ; Female ; Gene Targeting ; Male ; Maternal Behavior ; Membrane Proteins/*genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Mutation ; Neurons, Afferent/*physiology ; Odors ; Olfactory Bulb/physiology ; Olfactory Mucosa/physiology ; Pheromones/*physiology/urine ; Sex Characteristics ; *Sexual Behavior, Animal ; Signal Transduction ; TRPC Cation Channels ; Video Recording ; Vomeronasal Organ/*innervation/physiology
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Strauss, Evelyn -- New York, N.Y. -- Science. 2002 Jan 4;295(5552):28-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11778018" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*genetics ; Aging, Premature/genetics ; Animals ; Cell Division ; *Genes, p53 ; Longevity/genetics ; Mice ; Mutation ; Neoplasms/*genetics/prevention & control ; Tumor Suppressor Protein p53/*physiology
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  • 79
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-10-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2002 Oct 11;298(5592):341-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12376675" target="_blank"〉PubMed〈/a〉
    Keywords: Acetaminophen/administration & dosage/adverse effects/metabolism/*toxicity ; Analgesics, Non-Narcotic/administration & dosage/adverse ; effects/metabolism/toxicity ; Androstanols/pharmacology ; Animals ; Benzoquinones/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Drug Overdose ; Glutathione/metabolism ; Glutathione S-Transferase pi ; Glutathione Transferase/metabolism ; Humans ; Imines/metabolism ; Isoenzymes/metabolism ; Liver/*drug effects/*metabolism ; Liver Failure, Acute/*chemically induced ; Mice ; Mice, Transgenic ; Phenobarbital/metabolism/pharmacology ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/genetics/*metabolism ; Transcription Factors/antagonists & inhibitors/genetics/*metabolism
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  • 80
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-07-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2002 Jul 12;297(5579):174-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12114601" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Bioterrorism ; DNA, Viral/*chemical synthesis ; Databases, Nucleic Acid ; Mice ; Poliomyelitis/prevention & control/virology ; *Poliovirus/genetics/pathogenicity/physiology ; RNA, Viral/*chemical synthesis/*genetics ; Vaccination ; Variola virus ; Virulence ; Virus Assembly ; Virus Replication
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  • 81
    Publication Date: 2002-09-14
    Description: Mechanisms regulating self-renewal and cell fate decisions in mammalian stem cells are poorly understood. We determined global gene expression profiles for mouse and human hematopoietic stem cells and other stages of the hematopoietic hierarchy. Murine and human hematopoietic stem cells share a number of expressed gene products, which define key conserved regulatory pathways in this developmental system. Moreover, in the mouse, a portion of the genetic program of hematopoietic stem cells is shared with embryonic and neural stem cells. This overlapping set of gene products represents a molecular signature of stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ivanova, Natalia B -- Dimos, John T -- Schaniel, Christoph -- Hackney, Jason A -- Moore, Kateri A -- Lemischka, Ihor R -- DK42989/DK/NIDDK NIH HHS/ -- DK54493/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 18;298(5593):601-4. Epub 2002 Sep 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12228721" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Communication ; Cell Cycle ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cell Separation ; Cells, Cultured ; Computational Biology ; Embryo, Mammalian/cytology ; Expressed Sequence Tags ; *Gene Expression ; *Gene Expression Profiling ; Genes, Homeobox ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*physiology ; Humans ; Mice ; Neurons/cytology ; Oligonucleotide Array Sequence Analysis ; Signal Transduction ; Stem Cells/*physiology ; Totipotent Stem Cells/*physiology ; Transcription, Genetic
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  • 82
    Publication Date: 2002-04-06
    Description: Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at the site of tissue injury, and impaired activation of transforming growth factor-beta1. This phenotype was partially reversed by reconstitution with CD44+ cells, thus demonstrating a critical role for this receptor in resolving lung inflammation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teder, Priit -- Vandivier, R William -- Jiang, Dianhua -- Liang, Jiurong -- Cohn, Lauren -- Pure, Ellen -- Henson, Peter M -- Noble, Paul W -- HL60539/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Apr 5;296(5565):155-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11935029" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD44/*physiology ; Apoptosis ; Bleomycin ; Bone Marrow Transplantation ; Bronchoalveolar Lavage Fluid/chemistry/cytology ; Cell Count ; Chemokines/genetics/metabolism ; Chimera ; Humans ; Hyaluronic Acid/analysis/metabolism ; Lung/immunology/metabolism/*pathology ; Lung Diseases, Interstitial/*immunology/metabolism/*pathology ; Macrophages, Alveolar/physiology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration ; Neutrophils ; Phagocytosis ; Phenotype ; Pulmonary Alveoli/immunology/metabolism/pathology ; RNA, Messenger/genetics/metabolism ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta1
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  • 83
    Publication Date: 2002-10-12
    Description: We have identified the xenobiotic receptor CAR (constitutive androstane receptor) as a key regulator of acetaminophen metabolism and hepatotoxicity. Known CAR activators as well as high doses of acetaminophen induced expression of three acetaminophen-metabolizing enzymes in wild-type but not in CAR null mice, and the CAR null mice were resistant to acetaminophen toxicity. Inhibition of CAR activity by administration of the inverse agonist ligand androstanol 1 hour after acetaminophen treatment blocked hepatotoxicity in wild type but not in CAR null mice. These results suggest an innovative therapeutic approach for treating the adverse effects of acetaminophen and potentially other hepatotoxic agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jun -- Huang, Wendong -- Chua, Steven S -- Wei, Ping -- Moore, David D -- R01 DK46546/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 11;298(5592):422-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12376703" target="_blank"〉PubMed〈/a〉
    Keywords: Acetaminophen/metabolism/*toxicity ; Acetylcysteine/pharmacology ; Alanine Transaminase/blood ; Analgesics, Non-Narcotic/metabolism/toxicity ; Androstanols/pharmacology ; Animals ; Aryl Hydrocarbon Hydroxylases/genetics/metabolism ; Benzoquinones/metabolism ; Cytochrome P-450 CYP1A2/genetics/metabolism ; Cytochrome P-450 CYP2E1/genetics/metabolism ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System/genetics/metabolism ; Glutathione/metabolism ; Glutathione S-Transferase pi ; Glutathione Transferase/genetics/metabolism ; Humans ; Imines/metabolism ; Isoenzymes/genetics/metabolism ; Liver/*drug effects/*metabolism/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Oxidoreductases, N-Demethylating/genetics/metabolism ; Phenobarbital/pharmacology ; Pyridines/pharmacology ; RNA, Messenger/genetics/metabolism ; Receptors, Cytoplasmic and Nuclear/agonists/antagonists & ; inhibitors/genetics/*metabolism ; Time Factors ; Transcription Factors/agonists/antagonists & inhibitors/genetics/*metabolism
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  • 84
    Publication Date: 2002-02-09
    Description: Dip-pen nanolithography was used to construct arrays of proteins with 100- to 350-nanometer features. These nanoarrays exhibit almost no detectable nonspecific binding of proteins to their passivated portions even in complex mixtures of proteins, and therefore provide the opportunity to study a variety of surface-mediated biological recognition processes. For example, reactions involving the protein features and antigens in complex solutions can be screened easily by atomic force microscopy. As further proof-of-concept, these arrays were used to study cellular adhesion at the submicrometer scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Ki-Bum -- Park, So-Jung -- Mirkin, Chad A -- Smith, Jennifer C -- Mrksich, Milan -- New York, N.Y. -- Science. 2002 Mar 1;295(5560):1702-5. Epub 2002 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Northwestern University, Department of Chemistry and Center for Nanofabrication and Molecular Self-Assembly, 2145 Sheridan Road, Evanston, IL 60208, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834780" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Adsorption ; Animals ; Cell Adhesion ; *Fibronectins/chemistry/metabolism ; Focal Adhesions ; *Immunoglobulin G/chemistry/metabolism ; Mice ; Microscopy, Atomic Force ; Miniaturization ; *Muramidase/chemistry/metabolism ; *Nanotechnology ; Palmitic Acids/*chemistry ; Protein Binding ; *Proteins/chemistry/metabolism ; Receptor Aggregation ; Recombinant Proteins/chemistry/metabolism
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  • 85
    Publication Date: 2002-10-26
    Description: Obligate intracellular apicomplexan parasites rely on gliding motion powered by their actomyosin system to disperse throughout tissues and to penetrate host cells. Toxoplasma gondii myosin A has been implicated in this process, but direct proof has been lacking. We designed a genetic screen to generate a tetracycline-inducible transactivator system in T. gondii. The MyoA gene was disrupted in the presence of a second regulatable copy of MyoA. Conditional removal of this myosin caused severe impairment in host cell invasion and parasite spreading in cultured cells, and unambiguously established the pathogenic function of this motor in an animal model.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meissner, Markus -- Schluter, Dirk -- Soldati, Dominique -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):837-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Imperial College of Science, Technology and Medicine, Imperial College Road, London SW7 2AZ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12399593" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcimycin/pharmacology ; Calcium/metabolism ; Cell Line ; Cells, Cultured ; Exocytosis ; Genetic Vectors ; Humans ; Mice ; Movement ; Nonmuscle Myosin Type IIA/genetics/*physiology ; Organelles/metabolism ; Protozoan Proteins/genetics/physiology ; Tetracycline/pharmacology ; Toxoplasma/genetics/growth & development/*pathogenicity/*physiology ; Toxoplasmosis, Animal/*parasitology ; Trans-Activators/metabolism ; Transfection ; Transgenes ; Virulence ; Virulence Factors/*physiology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 86
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-10-26
    Description: In its earliest clinical phase, Alzheimer's disease characteristically produces a remarkably pure impairment of memory. Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid beta protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Selkoe, Dennis J -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):789-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurologic Diseases, Brigham and Women's Hospital, and the Harvard Center for Neurodegeneration and Repair, Boston, MA 02115, USA. selkoe@cnd.bwh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12399581" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/pathology/*physiopathology ; Amyloid beta-Peptides/genetics/*metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Animals ; Brain/pathology/*physiopathology ; Cognition ; Humans ; Long-Term Potentiation ; Membrane Proteins/genetics ; Memory ; Mice ; Mice, Transgenic ; Presenilin-1 ; Synapses/*physiology/ultrastructure ; Synaptic Transmission
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  • 87
    Publication Date: 2002-02-23
    Description: The area of contact between a T cell and an antigen-presenting cell (APC) is known as the immunological synapse. Although its exact function is unknown, one model suggests that it allows for T cell receptor (TCR) clustering and for sustained signaling in T cells for many hours. Here we demonstrate that TCR-mediated tyrosine kinase signaling in naive T cells occurred primarily at the periphery of the synapse and was largely abated before mature immunological synapses had formed. These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Kyeong-Hee -- Holdorf, Amy D -- Dustin, Michael L -- Chan, Andrew C -- Allen, Paul M -- Shaw, Andrey S -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1539-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, Box 8118, Saint Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11859198" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/*immunology ; Cell Division ; Cells, Cultured ; Down-Regulation ; Endocytosis ; Enzyme Activation ; Image Processing, Computer-Assisted ; Intercellular Junctions/*immunology/metabolism ; *Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1/metabolism ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism ; Mice ; Mice, Transgenic ; Peptides/immunology ; Protein-Tyrosine Kinases/metabolism ; Receptor Aggregation ; Receptors, Antigen, T-Cell/immunology/*metabolism ; *Signal Transduction ; T-Lymphocytes/*immunology/metabolism ; Time Factors ; ZAP-70 Protein-Tyrosine Kinase
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  • 88
    Publication Date: 2002-08-17
    Description: Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass spectrometry identified the active derivative of MMP-9, both in vitro and in vivo, as a stable sulfinic or sulfonic acid, whose formation was triggered by S-nitrosylation. These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gu, Zezong -- Kaul, Marcus -- Yan, Boxu -- Kridel, Steven J -- Cui, Jiankun -- Strongin, Alex -- Smith, Jeffrey W -- Liddington, Robert C -- Lipton, Stuart A -- AR08505/AR/NIAMS NIH HHS/ -- P01 HD29587/HD/NICHD NIH HHS/ -- R01 AR42750/AR/NIAMS NIH HHS/ -- R01 CA 69306/CA/NCI NIH HHS/ -- R01 EY05477/EY/NEI NIH HHS/ -- R01 EY09024/EY/NEI NIH HHS/ -- R01 NS41207/NS/NINDS NIH HHS/ -- T32 AG00252/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 16;297(5584):1186-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neuroscience and Aging, Program in Cell Adhesion and Extracellular Matrix Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12183632" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Brain Ischemia/*enzymology/pathology ; Cell Line ; Cells, Cultured ; Cerebral Cortex/blood supply/*enzymology/pathology ; Cysteine/*analogs & derivatives/metabolism/pharmacology ; Enzyme Activation ; Enzyme Precursors/genetics/metabolism ; Humans ; Matrix Metalloproteinase 9/chemistry/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Molecular ; Neurons/*physiology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Nitric Oxide Synthase Type I ; Oxidation-Reduction ; Phenylmercuric Acetate/*analogs & derivatives/pharmacology ; Rats ; Recombinant Proteins/metabolism ; Reperfusion ; S-Nitrosothiols/*metabolism/pharmacology ; Signal Transduction ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 89
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-05-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brophy, Peter J -- New York, N.Y. -- Science. 2002 May 3;296(5569):862-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Preclinical Veterinary Sciences, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK. peter.brophy@ed.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988561" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigens, Bacterial ; Axons/physiology ; Cell Death ; Cell Differentiation ; Cell Membrane/metabolism ; Coculture Techniques ; Cytoskeletal Proteins/metabolism ; Demyelinating Diseases/*microbiology ; Dystroglycans ; Dystrophin/metabolism ; Glycolipids/metabolism ; Humans ; Laminin/metabolism ; Leprosy/*microbiology/pathology/*physiopathology ; Membrane Glycoproteins/metabolism ; Membrane Proteins/metabolism ; Mice ; *Muscle Proteins ; Mycobacterium leprae/growth & development/metabolism/*pathogenicity ; Myelin Sheath/*physiology ; Schwann Cells/cytology/*microbiology/*physiology ; Utrophin
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  • 90
    Publication Date: 2002-02-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Der Merwe, P Anton -- Davis, Simon J -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1479-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. anton.vandermerwe@path.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11859183" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antigen-Presenting Cells/*immunology ; Antigens, CD ; Antigens, CD28/immunology/metabolism ; Antigens, CD80/immunology/metabolism ; Antigens, Differentiation/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; CTLA-4 Antigen ; Dimerization ; Histocompatibility Antigens Class II/metabolism ; *Immunoconjugates ; Immunoglobulin alpha-Chains/immunology/metabolism ; Intercellular Junctions/*immunology ; Ligands ; Lipid Bilayers ; Lymphocyte Activation ; Mice ; Peptides/immunology/metabolism ; Receptor Aggregation ; Receptors, Antigen, T-Cell/*immunology ; Signal Transduction ; T-Lymphocytes/*immunology ; Time Factors
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  • 91
    Publication Date: 2002-10-26
    Description: N-methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but also mediate essential neuronal excitation. To treat stroke without blocking NMDARs, we transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95. This procedure dissociated NMDARs from downstream neurotoxic signaling without blocking synaptic activity or calcium influx. The peptides, when applied either before or 1 hour after an insult, protected cultured neurons from excitotoxicity, reduced focal ischemic brain damage in rats, and improved their neurological function. This approach circumvents the negative consequences associated with blocking NMDARs and may constitute a practical stroke therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aarts, Michelle -- Liu, Yitao -- Liu, Lidong -- Besshoh, Shintaro -- Arundine, Mark -- Gurd, James W -- Wang, Yu-Tian -- Salter, Michael W -- Tymianski, Michael -- NS 39060/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):846-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Toronto Western Hospital Research Institute, 11-416 MC-PAV, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12399596" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Brain/*drug effects/metabolism ; Brain Ischemia/*drug therapy/metabolism ; Calcium/metabolism ; Cells, Cultured ; Cerebral Infarction/*drug therapy/metabolism ; Cyclic GMP/metabolism ; Guanylate Kinase ; In Vitro Techniques ; Intracellular Signaling Peptides and Proteins ; Male ; Membrane Proteins ; Mice ; Mice, Inbred C57BL ; N-Methylaspartate/pharmacology ; Nerve Tissue Proteins/chemistry/*metabolism ; Neurons/drug effects/physiology ; Patch-Clamp Techniques ; Peptides/administration & dosage/*pharmacology/therapeutic use ; Protein Binding ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*chemistry/*metabolism ; Recombinant Fusion Proteins/administration & dosage/pharmacology/therapeutic use ; Signal Transduction ; Synaptic Transmission/drug effects
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  • 92
    Publication Date: 2002-03-23
    Description: The deposition of amyloid-beta (Abeta) peptides into amyloid plaques precedes the cognitive dysfunction of Alzheimer's disease (AD) by years. Biomarkers indicative of brain amyloid burden could be useful for identifying individuals at high risk for developing AD. As in AD in humans, baseline plasma Abeta levels in a transgenic mouse model of AD did not correlate with brain amyloid burden. However, after peripheral administration of a monoclonal antibody to Abeta (m266), we observed a rapid increase in plasma Abeta and the magnitude of this increase was highly correlated with amyloid burden in the hippocampus and cortex. This method may be useful for quantifying brain amyloid burden in patients at risk for or those who have been diagnosed with AD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeMattos, Ronald B -- Bales, Kelly R -- Cummins, David J -- Paul, Steven M -- Holtzman, David M -- AG20222/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2002 Mar 22;295(5563):2264-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for the Study of Nervous System Injury, Alzheimer's Disease Research Center, Department of Neurology, Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11910111" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*blood/genetics/*metabolism/pathology ; Amino Acid Substitution ; Amyloid beta-Peptides/*blood/chemistry/genetics/*metabolism ; Amyloidosis/blood/genetics/metabolism/pathology ; Animals ; Antibodies, Monoclonal/immunology ; Brain/*metabolism/pathology ; Cerebral Cortex/metabolism/pathology ; *Disease Models, Animal ; Hippocampus/metabolism/pathology ; Humans ; Mice ; Protein Transport ; Solubility ; Time Factors
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  • 93
    Publication Date: 2002-12-10
    Description: Spermatogenesis is a highly specialized process of cellular differentiation to produce spermatozoa. This differentiation process accompanies morphological changes that are controlled by a number of genes expressed in a stage-specific manner during spermatogenesis. Here we show that in mice, the absence of a testis-specific, cytoplasmic polyadenylate [poly(A)] polymerase, TPAP, results in the arrest of spermiogenesis. TPAP-deficient mice display impaired expression of haploid-specific genes that are required for the morphogenesis of germ cells. The TPAP deficiency also causes incomplete elongation of poly(A) tails of particular transcription factor messenger RNAs. Although the overall cellular level of the transcription factor TAF10 is unaffected, TAF10 is insufficiently transported into the nucleus of germ cells. We propose that TPAP governs germ cell morphogenesis by modulating specific transcription factors at posttranscriptional and posttranslational levels.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kashiwabara, Shin-Ichi -- Noguchi, Junko -- Zhuang, Tiangang -- Ohmura, Ko -- Honda, Arata -- Sugiura, Shin -- Miyamoto, Kiyoko -- Takahashi, Satoru -- Inoue, Kimiko -- Ogura, Atsuo -- Baba, Tadashi -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):1999-2002.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Applied Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471261" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cytoplasm/enzymology ; Female ; Gene Expression Regulation, Developmental ; Gene Targeting ; In Situ Nick-End Labeling ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Nuclear Proteins/genetics/metabolism ; Organ Size ; Poly A/metabolism ; Polynucleotide Adenylyltransferase/genetics/*metabolism ; Protein Biosynthesis ; RNA, Messenger/*metabolism ; Spermatids/physiology ; Spermatocytes/physiology ; *Spermatogenesis ; Spermatozoa/*physiology ; Testis/*enzymology/metabolism ; Transcription Factors/genetics/metabolism ; Transcription, Genetic ; mRNA Cleavage and Polyadenylation Factors/genetics/metabolism
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  • 94
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2002 Jun 7;296(5574):1783-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12052928" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cholera/*microbiology ; Feces/*microbiology ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Gene Silencing ; Humans ; Intestines/*microbiology ; Mice ; Vibrio cholerae/genetics/growth & development/*pathogenicity/physiology ; Virulence
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  • 95
    Publication Date: 2002-09-07
    Description: Previous studies have revealed that autoantibodies, complement components, and Fc receptors each participate in the pathogenesis of erosive arthritis in K/BxN mice. However, it is not known which cellular populations are responsive to these inflammatory signals. We find that two strains of mice deficient in mast cells, W/Wv and Sl/Sld, were resistant to development of joint inflammation and that susceptibility was restored in the W/Wv strain by mast cell engraftment. Thus, mast cells may function as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, David M -- Friend, Daniel S -- Gurish, Michael F -- Benoist, Christophe -- Mathis, Diane -- Brenner, Michael B -- 1R01 AR/AI46580-01/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 6;297(5587):1689-92.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12215644" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/*immunology/pathology ; Autoantibodies/*immunology ; Blood Transfusion ; Bone Marrow Transplantation ; Cell Degranulation ; Joints/*immunology/pathology ; Male ; Mast Cells/*immunology/transplantation ; Mice ; Mice, Inbred C57BL
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  • 96
    Publication Date: 2002-08-17
    Description: In striated muscle, the plasma membrane forms tubular invaginations (transverse tubules or T-tubules) that function in depolarization-contraction coupling. Caveolin-3 and amphiphysin were implicated in their biogenesis. Amphiphysin isoforms have a putative role in membrane deformation at endocytic sites. An isoform of amphiphysin 2 concentrated at T-tubules induced tubular plasma membrane invaginations when expressed in nonmuscle cells. This property required exon 10, a phosphoinositide-binding module. In developing myotubes, amphiphysin 2 and caveolin-3 segregated in tubular and vesicular portions of the T-tubule system, respectively. These findings support a role of the bilayer-deforming properties of amphiphysin at T-tubules and, more generally, a physiological role of amphiphysin in membrane deformation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Eunkyung -- Marcucci, Melissa -- Daniell, Laurie -- Pypaert, Marc -- Weisz, Ora A -- Ochoa, Gian-Carlo -- Farsad, Khashayar -- Wenk, Markus R -- De Camilli, Pietro -- CA46128/CA/NCI NIH HHS/ -- NS36251/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 16;297(5584):1193-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12183633" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Caveolin 3 ; Caveolins/metabolism ; Cell Differentiation ; Cell Line ; Cell Membrane/metabolism ; Cell Membrane Structures/metabolism/*ultrastructure ; Cricetinae ; Dynamins ; Exons ; GTP Phosphohydrolases/metabolism ; Liposomes/metabolism ; Mice ; Microscopy, Electron ; Morphogenesis ; *Muscle Development ; Muscle, Skeletal/metabolism/*ultrastructure ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Protein Isoforms ; Protein Structure, Tertiary ; RNA, Small Interfering ; RNA, Untranslated/metabolism ; Recombinant Fusion Proteins/metabolism ; Transfection
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-08-24
    Description: The success of vertebrates was due in part to the acquisition and modification of jaws. Jaws are principally derived from the branchial arches, embryonic structures that exhibit proximodistal polarity. To investigate the mechanisms that specify the identity of skeletal elements within the arches, we examined mice lacking expression of Dlx5 and Dlx6, linked homeobox genes expressed distally but not proximally within the arches. Dlx5/6-/- mutants exhibit a homeotic transformation of lower jaws to upper jaws. We suggest that nested Dlx expression in the arches patterns their proximodistal axes. Evolutionary acquisition and subsequent refinement of jaws may have been dependent on modification of Dlx expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Depew, Michael J -- Lufkin, Thomas -- Rubenstein, John L R -- K02MH01046-01/MH/NIMH NIH HHS/ -- T32DE07204/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 11;298(5592):381-5. Epub 2002 Aug 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Nina Ireland Laboratory of Developmental Neurobiology, 401 Parnassus Avenue, University of California, San Francisco, San Francisco, CA 94143-0984, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12193642" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Evolution ; *Body Patterning ; Branchial Region/embryology/physiology ; Ear Ossicles/embryology ; Gene Deletion ; Gene Expression Regulation, Developmental ; *Genes, Homeobox ; Homeodomain Proteins/*genetics/physiology ; Mandible/anatomy & histology/*embryology ; Maxilla/anatomy & histology/*embryology ; Mice ; Morphogenesis ; Palate/embryology ; Skull/abnormalities/embryology ; Sphenoid Bone/embryology
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  • 98
    Publication Date: 2002-09-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gruber, Stephen B -- Ellis, Nathan A -- Scott, Karen K -- Almog, Ronit -- Kolachana, Prema -- Bonner, Joseph D -- Kirchhoff, Tomas -- Tomsho, Lynn P -- Nafa, Khedoudja -- Pierce, Heather -- Low, Marcelo -- Satagopan, Jaya -- Rennert, Hedy -- Huang, Helen -- Greenson, Joel K -- Groden, Joanna -- Rapaport, Beth -- Shia, Jinru -- Johnson, Stephen -- Gregersen, Peter K -- Harris, Curtis C -- Boyd, Jeff -- Rennert, Gad -- Offit, Kenneth -- R01CA81488/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2002 Sep 20;297(5589):2013.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Internal Medicine and Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12242432" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/*genetics ; Alleles ; Animals ; Bloom Syndrome/genetics ; Case-Control Studies ; Colorectal Neoplasms/*genetics ; DNA Helicases/*genetics ; Female ; Genes, APC ; *Genetic Predisposition to Disease ; *Heterozygote ; Humans ; Israel ; Jews/genetics ; Male ; Mice ; Mutation ; New York ; RecQ Helicases ; Risk Factors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2002-07-20
    Description: Mammalian organogenesis requires the expansion of pluripotent precursor cells before the subsequent determination of specific cell types, but the tissue-specific molecular mechanisms that regulate the initial expansion of primordial cells remain poorly defined. We have genetically established that Six6 homeodomain factor, acting as a strong tissue-specific repressor, regulates early progenitor cell proliferation during mammalian retinogenesis and pituitary development. Six6, in association with Dach corepressors, regulates proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. These data reveal a molecular mechanism by which a tissue-specific transcriptional repressor-corepressor complex can provide an organ-specific strategy for physiological expansion of precursor populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Xue -- Perissi, Valentina -- Liu, Forrest -- Rose, David W -- Rosenfeld, Michael G -- 484/B/Telethon/Italy -- 5F32DK09814/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 16;297(5584):1180-3. Epub 2002 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12130660" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Cycle ; Cell Cycle Proteins/genetics/metabolism ; *Cell Division ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Embryo, Mammalian/cytology ; Eye Proteins/metabolism ; Homeodomain Proteins/*genetics/*metabolism ; Mice ; Nuclear Proteins/metabolism ; Organ Specificity ; Pituitary Gland/*cytology/embryology ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/metabolism ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/metabolism ; Retina/*cytology/embryology ; Retinal Ganglion Cells/cytology/physiology ; Stem Cells/*physiology ; Trans-Activators/*genetics/*metabolism ; Transcription Factors ; Transcription, Genetic ; Transfection ; Tumor Suppressor Proteins/genetics/metabolism ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-02-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seydel, Caroline -- New York, N.Y. -- Science. 2002 Feb 22;295(5559):1451-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11859171" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cold Temperature ; Face/innervation ; Menthol/*metabolism/pharmacology ; Mice ; Neurons, Afferent/*physiology ; Potassium/metabolism ; Potassium Channels/*physiology ; Rats ; Receptors, Drug/*physiology ; Sensation/*physiology ; Thermoreceptors/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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