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  • Mutation  (125)
  • Male  (121)
  • Phenotype  (42)
  • American Association for the Advancement of Science (AAAS)  (253)
  • American Association of Petroleum Geologists (AAPG)
  • 2000-2004  (253)
  • 2000  (253)
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  • American Association for the Advancement of Science (AAAS)  (253)
  • American Association of Petroleum Geologists (AAPG)
  • Springer  (18)
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  • 2000-2004  (253)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-05
    Description: The assumption that human mitochondrial DNA is inherited from one parent only and therefore does not recombine is questionable. Linkage disequilibrium in human and chimpanzee mitochondrial DNA declines as a function of the distance between sites. This pattern can be attributed to one mechanism only: recombination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Awadalla, P -- Eyre-Walker, A -- Smith, J M -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2524-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 1JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617471" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; DNA, Mitochondrial/*genetics ; Evolution, Molecular ; Fathers ; Female ; Hominidae/*genetics ; Humans ; *Linkage Disequilibrium ; Male ; NADH Dehydrogenase/genetics ; Pan troglodytes/*genetics ; Polymorphism, Restriction Fragment Length ; *Recombination, Genetic
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  • 2
    Publication Date: 2000-01-05
    Description: Mice lacking mCry1 and mCry2 are behaviorally arrhythmic. As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and mPer2 mRNA levels are constitutively high. These findings indicate that the biological clock is eliminated in the absence of both mCRY1 and mCRY2 (mammalian cryptochromes 1 and 2) and support the idea that mammalian CRY proteins act in the negative limb of the circadian feedback loop. The mCry double-mutant mice retain the ability to have mPer1 and mPer2 expression induced by a brief light stimulus known to phase-shift the biological clock in wild-type animals. Thus, mCRY1 and mCRY2 are dispensable for light-induced phase shifting of the biological clock.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okamura, H -- Miyake, S -- Sumi, Y -- Yamaguchi, S -- Yasui, A -- Muijtjens, M -- Hoeijmakers, J H -- van der Horst, G T -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2531-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Brain Science, Kobe University School of Medicine, Kobe 650-0017, Japan. okamurah@kobe-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617474" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*physiology ; Cell Cycle Proteins ; Circadian Rhythm/*physiology ; Cryptochromes ; *Drosophila Proteins ; *Eye Proteins ; Feedback ; Flavoproteins/genetics/*physiology ; Gene Expression Regulation ; In Situ Hybridization ; *Light ; Liver/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation ; Nuclear Proteins/*genetics ; Period Circadian Proteins ; *Photoreceptor Cells, Invertebrate ; Polymerase Chain Reaction ; RNA, Messenger/genetics/metabolism ; Receptors, G-Protein-Coupled ; Retina/metabolism ; Suprachiasmatic Nucleus/metabolism ; Transcription Factors
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  • 3
    Publication Date: 2000-01-05
    Description: The nematode pharynx has a potassium channel with unusual properties, which allows the muscles to repolarize quickly and with the proper delay. Here, the Caenorhabditis elegans exp-2 gene is shown to encode this channel. EXP-2 is a Kv-type (voltage-activated) potassium channel that has inward-rectifying properties resembling those of the structurally dissimilar human ether-a-go-go-related gene (HERG) channel. Null and gain-of-function mutations affect pharyngeal muscle excitability in ways that are consistent with the electrophysiological behavior of the channel, and thereby demonstrate a direct link between the kinetics of this unusual channel and behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791429/" 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/PMC3791429/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, M W -- Fleischhauer, R -- Dent, J A -- Joho, R H -- Avery, L -- HL46154/HL/NHLBI NIH HHS/ -- NS28407/NS/NINDS NIH HHS/ -- R01 HL046154/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2501-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA. wdavis@biology.utah.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617464" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Feeding Behavior ; Genes, Helminth ; Genes, Reporter ; Ion Channel Gating ; Kinetics ; Membrane Potentials ; Models, Molecular ; Muscles/metabolism ; Mutation ; Neurons/metabolism ; Oocytes/metabolism ; Pharyngeal Muscles/physiology ; Potassium Channels/chemistry/genetics/*physiology ; Protein Conformation ; RNA, Complementary/genetics ; Recombinant Fusion Proteins/biosynthesis ; Xenopus laevis
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2434-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636797" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*physiology ; Brain/metabolism ; CLOCK Proteins ; Circadian Rhythm/*physiology ; Darkness ; Drosophila/genetics/physiology ; *Drosophila Proteins ; Gene Expression Regulation ; Genes, Insect ; Light ; Mutation ; Neurons/metabolism ; Neuropeptides/genetics/*physiology ; Transcription Factors/genetics/physiology
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  • 5
    Publication Date: 2000-03-24
    Description: Selective microtubule orientation toward spatially defined cortical sites is critical to polarized cellular processes as diverse as axon outgrowth and T cell cytotoxicity. In yeast, oriented cytoplasmic microtubules align the mitotic spindle between mother and bud. The cortical marker protein Kar9 localizes to the bud tip and is required for the orientation of microtubules toward this region. Here, we show that Kar9 directs microtubule orientation by acting through Bim1, a conserved microtubule-binding protein. Bim1 homolog EB1 was originally identified through its interaction with adenomatous polyposis coli (APC) tumor suppressor, raising the possibility that an APC-EB1 linkage orients microtubules in higher cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korinek, W S -- Copeland, M J -- Chaudhuri, A -- Chant, J -- GM07620-19/GM/NIGMS NIH HHS/ -- GM07620-20/GM/NIGMS NIH HHS/ -- GM49782/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2257-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10731146" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein ; Cell Cycle Proteins/genetics/*metabolism ; Cell Nucleus/physiology ; Cytoskeletal Proteins/metabolism ; Microtubule Proteins/genetics/*metabolism ; Microtubule-Associated Proteins/metabolism ; Microtubules/metabolism/*physiology ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Phenotype ; Protein Binding ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/cytology/genetics/*physiology ; *Saccharomyces cerevisiae Proteins ; Spindle Apparatus/*physiology ; Two-Hybrid System Techniques
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Mutation at the mouse progressive ankylosis (ank) locus causes a generalized, progressive form of arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction. Here, we show that the ank locus encodes a multipass transmembrane protein (ANK) that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. A highly conserved gene is present in humans and other vertebrates. These results identify ANK-mediated control of pyrophosphate levels as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, A M -- Johnson, M D -- Kingsley, D M -- 5T32GM07365/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):265-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology and Howard Hughes Medical Institute, Beckman Center B300, Stanford University School of Medicine, Stanford, CA 94305-5327, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894769" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis/*genetics/metabolism/pathology ; Base Sequence ; Biological Transport ; COS Cells ; Calcinosis/*genetics ; Chromosome Mapping ; Cloning, Molecular ; Dna ; Diphosphates/*metabolism ; Durapatite/metabolism ; Gene Expression ; Genetic Complementation Test ; Humans ; Membrane Proteins/*genetics/metabolism/*physiology ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation ; Phenotype ; Phosphate Transport Proteins ; Physical Chromosome Mapping ; Sequence Homology, Nucleic Acid ; Tissue Distribution
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  • 7
    Publication Date: 2000-08-01
    Description: The path of the nucleic acids through a transcription elongation complex was tracked by mapping cross-links between bacterial RNA polymerase (RNAP) and transcript RNA or template DNA onto the x-ray crystal structure. In the resulting model, the downstream duplex DNA is nestled in a trough formed by the beta' subunit and enclosed on top by the beta subunit. In the RNAP channel, the RNA/DNA hybrid extends from the enzyme active site, along a region of the beta subunit harboring rifampicin resistance mutations, to the beta' subunit "rudder." The single-stranded RNA is then extruded through another channel formed by the beta-subunit flap domain. The model provides insight into the functional properties of the transcription complex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Korzheva, N -- Mustaev, A -- Kozlov, M -- Malhotra, A -- Nikiforov, V -- Goldfarb, A -- Darst, S A -- GM30717/GM/NIGMS NIH HHS/ -- GM49242/GM/NIGMS NIH HHS/ -- GM53759/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):619-25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Public Health Research Institute, 455 First Avenue, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10915625" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Cross-Linking Reagents ; Crystallography, X-Ray ; DNA/chemistry/genetics/*metabolism ; DNA Primers ; DNA-Directed RNA Polymerases/*chemistry/genetics/metabolism ; Models, Molecular ; Mutation ; Nucleic Acid Conformation ; Nucleic Acid Hybridization ; Oligodeoxyribonucleotides/chemistry/metabolism ; Oligoribonucleotides/chemistry/metabolism ; Protein Conformation ; Protein Structure, Tertiary ; RNA, Messenger/chemistry/genetics/*metabolism ; Templates, Genetic ; Thermus/enzymology ; *Transcription, Genetic
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-24
    Description: The 120-megabase euchromatic portion of the Drosophila melanogaster genome has been sequenced. Because the genome is compact and many genetic tools are available, and because fly cell biology and development have much in common with mammals, this sequence may be the Rosetta stone for deciphering the human genome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kornberg, T B -- Krasnow, M A -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2218-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10731136" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biology ; Cloning, Molecular ; DNA Transposable Elements ; Drosophila melanogaster/*genetics/physiology ; Genes, Insect ; *Genetics, Medical ; *Genome ; *Genome, Human ; Humans ; Mutation ; Physical Chromosome Mapping ; *Sequence Analysis, DNA
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  • 9
    Publication Date: 2000-03-17
    Description: Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuoka, T -- Hirata, M -- Tanaka, H -- Takahashi, Y -- Murata, T -- Kabashima, K -- Sugimoto, Y -- Kobayashi, T -- Ushikubi, F -- Aze, Y -- Eguchi, N -- Urade, Y -- Yoshida, N -- Kimura, K -- Mizoguchi, A -- Honda, Y -- Nagai, H -- Narumiya, S -- New York, N.Y. -- Science. 2000 Mar 17;287(5460):2013-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10720327" target="_blank"〉PubMed〈/a〉
    Keywords: Allergens/immunology ; Animals ; Asthma/immunology/metabolism/pathology/*physiopathology ; Bronchial Hyperreactivity ; Bronchoalveolar Lavage Fluid/cytology/immunology ; Crosses, Genetic ; Female ; Gene Targeting ; Humans ; Immunoglobulin E/blood ; Interferon-gamma/metabolism ; Interleukins/metabolism ; Lung/immunology/metabolism/pathology ; Lymphocytes/immunology ; Male ; Mast Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Mucus/secretion ; Ovalbumin/immunology ; Prostaglandin D2/metabolism/*physiology ; *Receptors, Immunologic ; Receptors, Prostaglandin/genetics/metabolism/*physiology ; Respiratory Mucosa/secretion
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Persaud, R -- New York, N.Y. -- Science. 2000 May 12;288(5468):975.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10841715" target="_blank"〉PubMed〈/a〉
    Keywords: Canada/epidemiology ; Depression/*epidemiology/etiology ; Depressive Disorder/*epidemiology/etiology ; Female ; Humans ; Male
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  • 11
    Publication Date: 2000-09-01
    Description: Activation of the transcription factor nuclear factor (NF)-kappaB by proinflammatory stimuli leads to increased expression of genes involved in inflammation. Activation of NF-kappaB requires the activity of an inhibitor of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier). An amino-terminal alpha-helical region of NEMO associated with a carboxyl-terminal segment of IKKalpha and IKKbeta that we term the NEMO-binding domain (NBD). A cell-permeable NBD peptide blocked association of NEMO with the IKK complex and inhibited cytokine-induced NF-kappaB activation and NF-kappaB-dependent gene expression. The peptide also ameliorated inflammatory responses in two experimental mouse models of acute inflammation. The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉May, M J -- D'Acquisto, F -- Madge, L A -- Glockner, J -- Pober, J S -- Ghosh, S -- AI 33443/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1550-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968790" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemistry/pharmacology ; COS Cells ; Cells, Cultured ; E-Selectin/biosynthesis/genetics ; Endothelium, Vascular/metabolism ; Gene Expression Regulation ; HeLa Cells ; Humans ; I-kappa B Kinase ; Inflammation/drug therapy ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Mutation ; NF-kappa B/*metabolism ; Peptides/chemistry/*pharmacology ; Point Mutation ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry/genetics/*metabolism ; Recombinant Fusion Proteins/metabolism
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  • 12
    Publication Date: 2000-03-31
    Description: The maternal determinant Bicoid (Bcd) represents the paradigm of a morphogen that provides positional information for pattern formation. However, as bicoid seems to be a recently acquired gene in flies, the question was raised as to how embryonic patterning is achieved in organisms with more ancestral modes of development. Because the phylogenetically conserved Hunchback (Hb) protein had previously been shown to act as a morphogen in abdominal patterning, we asked which functions of Bcd could be performed by Hb. By reestablishing a proposed ancient regulatory circuitry in which maternal Hb controls zygotic hunchback expression, we show that Hb is able to form thoracic segments in the absence of Bcd.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wimmer, E A -- Carleton, A -- Harjes, P -- Turner, T -- Desplan, C -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2476-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lehrstuhl Genetik, Universitat Bayreuth, 95447 Bayreuth, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10741965" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Body Patterning ; DNA-Binding Proteins/genetics/*physiology ; Drosophila/*embryology/genetics ; *Drosophila Proteins ; Embryonic Development ; Female ; Gene Expression Regulation, Developmental ; Genes, Insect ; Homeodomain Proteins/genetics/*physiology ; Insect Proteins/genetics/*physiology ; Male ; Mutation ; Phenotype ; Promoter Regions, Genetic ; Thorax/embryology ; Trans-Activators/genetics/*physiology ; Transcription Factors/genetics/*physiology ; Transgenes ; Zinc Fingers ; Zygote/physiology
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  • 13
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: On page 441 of this issue, evolutionary biologists showcase the purple-throated carib hummingbird as a rare example of food supply--in this case, flower shape--spurring the evolution of a sexual dimorphism, or a feature that differs between males and females. On St. Lucia, an island in the West Indies, female caribs sport bills a third longer and twice as curved as those of their male counterparts--one of the most extreme bill differences between the sexes in any hummingbird species. In the paper, the researchers link these "whoppingly dimorphic bills" to the specific flowers the male and female caribs frequent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brown, K -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):369-71.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939937" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Beak/*anatomy & histology ; *Biological Evolution ; Birds/*anatomy & histology/physiology ; Ecosystem ; Feeding Behavior ; Female ; Male ; Plant Structures/anatomy & histology ; Saint Lucia ; *Sex Characteristics ; Zingiberales/*anatomy & histology
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: Experts in the young field of violence epidemiology blame guns and crack cocaine for America's deadly crime surge in the early 1990s. Explaining the subsequent decline in violent crime rates has been more difficult, however. Some of the factors that seem to have helped squelch crime could be temporary, such as low unemployment rates. But others, including a growing intolerance for violence as a means of settling interpersonal disputes, seem to have become cultural norms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmuth, L -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):582-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939973" target="_blank"〉PubMed〈/a〉
    Keywords: Abortion, Legal ; Crack Cocaine ; Domestic Violence/statistics & numerical data ; Female ; Firearms ; Homicide/*statistics & numerical data ; Humans ; Male ; Police ; Prisons ; Street Drugs ; United States ; Violence/*statistics & numerical data
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  • 15
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sodha, N -- Williams, R -- Mangion, J -- Bullock, S L -- Yuille, M R -- Eeles, R A -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):359.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Royal Marsden NHS Trust, Sutton, Surrey SM2 5PT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939935" target="_blank"〉PubMed〈/a〉
    Keywords: Checkpoint Kinase 2 ; Chromosomes, Human, Pair 15/genetics ; DNA Mutational Analysis ; Exons ; Gene Duplication ; Genetic Variation ; Humans ; Li-Fraumeni Syndrome/*genetics ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Protein Kinases/*genetics ; *Protein-Serine-Threonine Kinases ; Sequence Homology, Nucleic Acid
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  • 16
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-10-14
    Description: Model organisms such as yeast have proved exceptionally valuable for revealing new information about the molecular pathways involved in the aging of cells. In her Perspective, Campisi comments on new work showing that caloric restriction increases longevity in yeast by activating the SIR2 gene, which alters the compactness of chromatin and thus regulates gene expression (Lin et al.).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Campisi, J -- New York, N.Y. -- Science. 2000 Sep 22;289(5487):2062-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. jcampisi@lbl.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11032557" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*physiology ; Animals ; Cell Division ; Chromatin/*physiology ; DNA Repair ; DNA Replication ; DNA, Circular/metabolism ; DNA, Fungal/metabolism ; DNA, Ribosomal/metabolism ; *Energy Intake ; *Gene Silencing ; Glucose/metabolism ; Histone Deacetylases/genetics/*metabolism ; Histones/metabolism ; Longevity ; Mutation ; NAD/metabolism ; Reactive Oxygen Species/metabolism ; Recombination, Genetic ; Saccharomyces cerevisiae/genetics/*physiology ; *Silent Information Regulator Proteins, Saccharomyces cerevisiae ; Sirtuin 2 ; Sirtuins ; Trans-Activators/genetics/*metabolism
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  • 17
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: Some 110 scientists from a range of disciplines gathered in the overcast British midlands for the 5th International Ancient DNA Conference, held here from 12 to 14 July. Among the attractions were new insights into the diets of early Americans gleaned from ancient human coprolites and intriguing reports of nuclear DNA and ancient viral sequences extracted from mammoth bones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stokstad, E -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):530-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939960" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone and Bones/virology ; DNA/*analysis/history ; DNA, Viral/analysis/*history ; Diet/*history ; Elephants/*genetics/virology ; Feces/*chemistry ; Female ; Fossils ; History, Ancient ; Humans ; Male ; Texas
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  • 18
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-29
    Description: A fundamental question in aging research is whether humans and other species possess an immutable life-span limit. We examined the maximum age at death in Sweden, which rose from about 101 years during the 1860s to about 108 years during the 1990s. The pace of increase was 0.44 years per decade before 1969 but accelerated to 1. 11 years per decade after that date. More than 70 percent of the rise in the maximum age at death from 1861 to 1999 is attributable to reductions in death rates above age 70. The rest are due to increased numbers of survivors to old age (both larger birth cohorts and increased survivorship from infancy to age 70). The more rapid rise in the maximum age since 1969 is due to the faster pace of old-age mortality decline during recent decades.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilmoth, J R -- Deegan, L J -- Lundstrom, H -- Horiuchi, S -- K02-AG00778/AG/NIA NIH HHS/ -- R01-AG11552/AG/NIA NIH HHS/ -- R01-AG14698/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 29;289(5488):2366-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Demography, University of California, Berkeley, CA 94720-2120, USA. jrw@demog.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11009426" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Humans ; Life Expectancy/trends ; Life Tables ; *Longevity ; Male ; Mortality/trends ; Probability ; Sweden
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  • 19
    Publication Date: 2000-05-29
    Description: Pathogenic mycobacteria, including the agent of tuberculosis, Mycobacterium tuberculosis, must replicate in macrophages for long-term persistence within their niche during chronic infection: organized collections of macrophages and lymphocytes called granulomas. We identified several genes preferentially expressed when Mycobacterium marinum, the cause of fish and amphibian tuberculosis, resides in host granulomas and/or macrophages. Two were homologs of M. tuberculosis PE/PE-PGRS genes, a family encoding numerous repetitive glycine-rich proteins of unknown function. Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophages and with decreased persistence in granulomas. Our results establish a direct role in virulence for some PE-PGRS proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramakrishnan, L -- Federspiel, N A -- Falkow, S -- AI 32396/AI/NIAID NIH HHS/ -- K08 AI 01400/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 May 26;288(5470):1436-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. lalitar@cmgm.stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10827956" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/chemistry/*genetics ; Cells, Cultured ; Disease Models, Animal ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Glycine/analysis ; Granuloma/*microbiology/pathology ; Humans ; Macrophages/*microbiology ; Mutation ; Mycobacterium Infections, Nontuberculous/*microbiology/pathology ; Mycobacterium marinum/*genetics/growth & development/*pathogenicity ; Mycobacterium tuberculosis/genetics/pathogenicity ; Promoter Regions, Genetic ; Rana pipiens ; Tuberculosis/microbiology ; Virulence
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-02-26
    Description: Repetition priming has been characterized neurophysiologically as a decreased response following stimulus repetition. The present study used event-related functional magnetic resonance imaging to investigate whether this repetition-related response is sensitive to stimulus familiarity. A right fusiform region exhibited an attenuated response to the repetition of familiar stimuli, both faces and symbols, but exhibited an enhanced response to the repetition of unfamiliar stimuli. Moreover, both repetition effects were modulated by lag between successive presentations. Further experiments replicated the interactions between repetition, familiarity, and lag and demonstrated the persistence of these effects over multiple repetitions. Priming-related responses are therefore not unitary but depend on the presence or absence of preexisting stimulus representations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Henson, R -- Shallice, T -- Dolan, R -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1269-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Department of Cognitive Neurology, Institute of Neurology, Institute of Cognitive Neuroscience and Department of Psychology, University College London, London WC1E 6BT, UK. r.henson@ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678834" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain Mapping ; Face ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Memory/*physiology ; *Pattern Recognition, Visual ; Regression Analysis ; Temporal Lobe/*physiology ; Time Factors
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  • 21
    Publication Date: 2000-02-26
    Description: The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line-derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonial cells that include the stem cells for spermatogenesis. Gene-targeted mice with one GDNF-null allele show depletion of stem cell reserves, whereas mice overexpressing GDNF show accumulation of undifferentiated spermatogonia. They are unable to respond properly to differentiation signals and undergo apoptosis upon retinoic acid treatment. Nonmetastatic testicular tumors are regularly formed in older GDNF-overexpressing mice. Thus, GDNF contributes to paracrine regulation of spermatogonial self-renewal and differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meng, X -- Lindahl, M -- Hyvonen, M E -- Parvinen, M -- de Rooij, D G -- Hess, M W -- Raatikainen-Ahokas, A -- Sainio, K -- Rauvala, H -- Lakso, M -- Pichel, J G -- Westphal, H -- Saarma, M -- Sariola, H -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1489-93.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Programs of Developmental Biology, Molecular Neurobiology, Electron Microscopy Unit, Institute of Biotechnology, Viikki Biocenter, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688798" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/drug effects ; Cell Cycle ; Cell Differentiation/drug effects ; Cobalt/metabolism ; *Drosophila Proteins ; Female ; Gene Expression ; Gene Targeting ; Glial Cell Line-Derived Neurotrophic Factor ; Glial Cell Line-Derived Neurotrophic Factor Receptors ; Male ; Mice ; Mice, Transgenic ; Mitosis ; *Nerve Growth Factors ; Nerve Tissue Proteins/genetics/*physiology ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins c-ret ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; Sertoli Cells/cytology/physiology ; *Spermatogenesis ; Spermatogonia/*cytology/drug effects ; Stem Cells/*cytology ; Testicular Neoplasms/pathology ; Testis/anatomy & histology ; Vitamin A/pharmacology
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  • 22
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-10-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, R -- New York, N.Y. -- Science. 2000 Sep 29;289(5488):2253-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11041782" target="_blank"〉PubMed〈/a〉
    Keywords: DNA, Mitochondrial/genetics ; Europe ; History, Ancient ; Humans ; Ice ; Italy ; Male ; *Mummies ; Paleodontology ; Paleopathology
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  • 23
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-10-13
    Description: Stromal cells are thought to generate specific regulatory microenviroments or "niches" that control stem cell behavior. Characterizing stem cell niches in vivo remains an important goal that has been difficult to achieve. The individual ovarioles of the Drosophila ovary each contain about two germ line stem cells that maintain oocyte production. Here we show that anterior ovariolar somatic cells comprising three cell types act as a germ line stem cell niche. Germ line stem cells lost by normal or induced differentiation are efficiently replaced, and the ability to repopulate the niche increases the functional lifetime of ovarioles in vivo. Our studies implicate one of the somatic cell types, the cap cells, as a key niche component.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xie, T -- Spradling, A C -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2000 Oct 13;290(5490):328-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Embryology, Howard Hughes Medical Institute, Carnegie Institution of Washington, 115 West University Parkway, Baltimore, MD 21210, USA. tgx@stowers-institute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11030649" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Cell Communication ; Cell Differentiation ; Drosophila/*cytology/physiology ; Female ; Germ Cells/*cytology/physiology ; Intercellular Junctions/physiology ; Models, Biological ; Mutation ; Oocytes/*cytology/physiology ; Ovary/cytology ; Stem Cells/*cytology/physiology ; Stromal Cells/cytology/physiology ; Transgenes
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  • 24
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LeClerc, J E -- Cebula, T A -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):391-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939947" target="_blank"〉PubMed〈/a〉
    Keywords: *Adenosine Triphosphatases ; Bacterial Proteins/genetics ; Base Pair Mismatch ; Chronic Disease ; Cystic Fibrosis/complications/*microbiology ; DNA Repair ; *DNA-Binding Proteins ; *Escherichia coli Proteins ; Humans ; Lung/*microbiology ; MutS DNA Mismatch-Binding Protein ; *Mutation ; Phenotype ; Pseudomonas Infections/complications/*microbiology ; Pseudomonas aeruginosa/*genetics ; *Recombination, Genetic ; Selection, Genetic
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yan, H -- Kinzler, K W -- Vogelstein, B -- New York, N.Y. -- Science. 2000 Sep 15;289(5486):1890-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and the Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11012364" target="_blank"〉PubMed〈/a〉
    Keywords: Genetic Techniques ; *Genetic Testing/methods ; *Genetics, Medical/trends ; Humans ; Mutation ; Sociology
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  • 26
    Publication Date: 2000-07-06
    Description: A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-alpha and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chan, F K -- Chun, H J -- Zheng, L -- Siegel, R M -- Bui, K L -- Lenardo, M J -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2351-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875917" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Antigens, CD/chemistry/metabolism ; Apoptosis ; Binding Sites ; Cross-Linking Reagents ; Dimerization ; Energy Transfer ; Fluorescence ; Humans ; Ligands ; Macromolecular Substances ; Mutation ; Protein Conformation ; Protein Structure, Tertiary ; Receptors, Tumor Necrosis Factor/*chemistry/*metabolism ; Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; Recombinant Fusion Proteins/chemistry/metabolism ; *Signal Transduction ; Succinimides ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/*metabolism
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  • 27
    Publication Date: 2000-07-15
    Description: Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lopez-Coviella, I -- Berse, B -- Krauss, R -- Thies, R S -- Blusztajn, J K -- P01 AG09525/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):313-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894782" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/biosynthesis ; Animals ; Bone Morphogenetic Proteins/*physiology ; Carrier Proteins/genetics ; Cells, Cultured ; Central Nervous System ; Choline O-Acetyltransferase/genetics ; Embryo, Mammalian/metabolism ; Fibroblast Growth Factor 2/physiology ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Growth Differentiation Factor 2 ; *Membrane Transport Proteins ; Mice ; Neurons/metabolism ; Phenotype ; RNA, Messenger/metabolism ; Septum of Brain/embryology/metabolism ; Spinal Cord/embryology/metabolism ; Up-Regulation ; Vesicular Acetylcholine Transport Proteins ; *Vesicular Transport Proteins
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  • 28
    Publication Date: 2000-11-25
    Description: We generated a mutant of the red fluorescent protein drFP583. The mutant (E5) changes its fluorescence from green to red over time. The rate of color conversion is independent of protein concentration and therefore can be used to trace time-dependent expression. We used in vivo labeling with E5 to measure expression from the heat shock-dependent promoter in Caenorhabditis elegans and from the Otx-2 promoter in developing Xenopus embryos. Thus, E5 is a "fluorescent timer" that can be used to monitor both activation and down-regulation of target promoters on the whole-organism scale.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Terskikh, A -- Fradkov, A -- Ermakova, G -- Zaraisky, A -- Tan, P -- Kajava, A V -- Zhao, X -- Lukyanov, S -- Matz, M -- Kim, S -- Weissman, I -- Siebert, P -- 1 RO3 TW01362-01/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1585-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine, Stanford University, Stanford, CA 94305, USA. Alexey.Terskikh@Stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090358" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/embryology/metabolism ; Caenorhabditis elegans/embryology/genetics ; Cell Line ; Color ; Fluorescence ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Gene Expression Regulation, Developmental ; Heat-Shock Proteins/genetics ; *Homeodomain Proteins ; Humans ; Luminescent Proteins/*chemistry/*genetics/metabolism ; Mutation ; Nerve Tissue Proteins/genetics ; Otx Transcription Factors ; *Promoter Regions, Genetic ; Temperature ; Time Factors ; Trans-Activators/genetics ; Xenopus laevis/embryology
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  • 29
    Publication Date: 2000-03-10
    Description: The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tettelin, H -- Saunders, N J -- Heidelberg, J -- Jeffries, A C -- Nelson, K E -- Eisen, J A -- Ketchum, K A -- Hood, D W -- Peden, J F -- Dodson, R J -- Nelson, W C -- Gwinn, M L -- DeBoy, R -- Peterson, J D -- Hickey, E K -- Haft, D H -- Salzberg, S L -- White, O -- Fleischmann, R D -- Dougherty, B A -- Mason, T -- Ciecko, A -- Parksey, D S -- Blair, E -- Cittone, H -- Clark, E B -- Cotton, M D -- Utterback, T R -- Khouri, H -- Qin, H -- Vamathevan, J -- Gill, J -- Scarlato, V -- Masignani, V -- Pizza, M -- Grandi, G -- Sun, L -- Smith, H O -- Fraser, C M -- Moxon, E R -- Rappuoli, R -- Venter, J C -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1809-15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Institute for Genomic Research (TIGR), 9712 Medical Center Drive, Rockville, MD 20850, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710307" target="_blank"〉PubMed〈/a〉
    Keywords: Antigenic Variation ; Antigens, Bacterial/immunology ; Bacteremia/microbiology ; Bacterial Capsules/genetics ; Bacterial Proteins/genetics/physiology ; DNA Transposable Elements ; Evolution, Molecular ; Fimbriae, Bacterial/genetics ; *Genome, Bacterial ; Humans ; Meningitis, Meningococcal/microbiology ; Meningococcal Infections/microbiology ; Molecular Sequence Data ; Mutation ; Neisseria meningitidis/classification/*genetics/*pathogenicity/physiology ; Open Reading Frames ; Operon ; Phylogeny ; Recombination, Genetic ; *Sequence Analysis, DNA ; Serotyping ; Transformation, Bacterial ; Virulence/genetics
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  • 30
    Publication Date: 2000-11-04
    Description: Construction of four dams on the lower Snake River (in northwestern United States) between 1961 and 1975 altered salmon spawning habitat, elevated smolt and adult migration mortality, and contributed to severe declines of Snake River salmon populations. By applying a matrix model to long-term population data, we found that (i) dam passage improvements have dramatically mitigated direct mortality associated with dams; (ii) even if main stem survival were elevated to 100%, Snake River spring/summer chinook salmon (Oncorhynchus tshawytscha) would probably continue to decline toward extinction; and (iii) modest reductions in first-year mortality or estuarine mortality would reverse current population declines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kareiva, P -- Marvier, M -- McClure, M -- New York, N.Y. -- Science. 2000 Nov 3;290(5493):977-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Marine Fisheries Service, Northwest Fisheries Science Center, 2725 Montlake Boulevard East, Seattle, WA 98112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11062128" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Conservation of Natural Resources ; *Ecosystem ; Female ; Fresh Water ; Male ; Models, Biological ; Models, Statistical ; Northwestern United States ; Population Dynamics ; *Salmon/growth & development/physiology ; Survival Rate
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  • 31
    Publication Date: 2000-03-31
    Description: A major modification to the sterile insect technique is described, in which transgenic insects homozygous for a dominant, repressible, female-specific lethal gene system are used. We demonstrate two methods that give the required genetic characteristics in an otherwise wild-type genetic background. The first system uses a sex-specific promoter or enhancer to drive the expression of a repressible transcription factor, which in turn controls the expression of a toxic gene product. The second system uses non-sex-specific expression of the repressible transcription factor to regulate a selectively lethal gene product. Both methods work efficiently in Drosophila melanogaster, and we expect these principles to be widely applicable to more economically important organisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thomas, D D -- Donnelly, C A -- Wood, R J -- Alphey, L S -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2474-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10741964" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Crosses, Genetic ; DNA-Binding Proteins ; *Drosophila Proteins ; Drosophila melanogaster/*genetics ; Egg Proteins/genetics ; Enhancer Elements, Genetic ; Fat Body/metabolism ; Female ; Gene Expression Regulation ; *Genes, Dominant ; *Genes, Insect ; *Genes, Lethal ; Genes, ras ; Homozygote ; Male ; Models, Biological ; Nuclear Proteins/genetics ; *Pest Control, Biological ; Promoter Regions, Genetic ; Tetracycline/pharmacology ; Trans-Activators/genetics ; Transcription Factors/genetics
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Many South Africans long dreamed of the day when the oppressive apartheid system would end. That day has come, but now the country faces a new disaster: one of the world's worst HIV epidemics--and most confusing government responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, J -- New York, N.Y. -- Science. 2000 Jun 23;288(5474):2168-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10896606" target="_blank"〉PubMed〈/a〉
    Keywords: *Acquired Immunodeficiency Syndrome/epidemiology ; Anti-HIV Agents/therapeutic use ; Disease Outbreaks ; Female ; Government ; HIV Infections/drug therapy/epidemiology ; Humans ; Male ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy ; Public Policy ; *Research ; South Africa/epidemiology
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmer, C -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):525-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939959" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Behavior, Animal ; Biological Evolution ; *Fear ; Female ; Humans ; Male ; *Personality ; Rats ; Toxoplasma/*physiology ; Toxoplasmosis, Animal/parasitology/*psychology ; Toxoplasmosis, Cerebral/parasitology/*psychology
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  • 34
    Publication Date: 2000-06-10
    Description: Theories of the regulation of cognition suggest a system with two necessary components: one to implement control and another to monitor performance and signal when adjustments in control are needed. Event-related functional magnetic resonance imaging and a task-switching version of the Stroop task were used to examine whether these components of cognitive control have distinct neural bases in the human brain. A double dissociation was found. During task preparation, the left dorsolateral prefrontal cortex (Brodmann's area 9) was more active for color naming than for word reading, consistent with a role in the implementation of control. In contrast, the anterior cingulate cortex (Brodmann's areas 24 and 32) was more active when responding to incongruent stimuli, consistent with a role in performance monitoring.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacDonald, A W 3rd -- Cohen, J D -- Stenger, V A -- Carter, C S -- New York, N.Y. -- Science. 2000 Jun 9;288(5472):1835-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10846167" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Brain Mapping ; Cerebral Cortex/*physiology ; Cognition/*physiology ; Color ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Prefrontal Cortex/*physiology ; Reading
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  • 35
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-19
    Description: A task force here has been studying cases of variant Creutzfeldt-Jakob disease (vCJD), an incurable malady of the brain and nervous system that has been linked to eating beef or other products from cattle infected with bovine spongiform encephalopathy or "mad cow disease." The team's goal is to find out just how the patients got infected and how many of them there may ultimately be. The number of confirmed or probable vCJD cases in the United Kingdom is still relatively small--a total of 80 as Science went to press--and recent estimates of the number of potential cases are lower than was once feared. Yet the task force's own recent results show that the incidence of vCJD is rising, and researchers remain determined to try to solve the riddles posed by vCJD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, M -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1452-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10991726" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bias (Epidemiology) ; Cattle ; Cluster Analysis ; Creutzfeldt-Jakob Syndrome/*epidemiology/transmission ; Disease Outbreaks ; Encephalopathy, Bovine Spongiform/epidemiology/transmission ; Female ; *Food ; Great Britain/epidemiology ; Humans ; Incidence ; Male ; Meat ; Surveys and Questionnaires
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  • 36
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Certain genes are only expressed at one allele, a phenomenon called imprinting. Although it is well established that one allele of certain imprinted genes is silenced through methylation, this does not appear to be the case for all imprinted genes. In a thoughtful Perspective, Thorvaldsen and Bartolomei discuss new findings showing that insertion of insulator elements (boundary regions) between the promoter of a gene and its enhancer (a sequence that boosts gene expression) may be another way in which genes are silenced during imprinting.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thorvaldsen, J L -- Bartolomei, M S -- New York, N.Y. -- Science. 2000 Jun 23;288(5474):2145-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. thorvald@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10896590" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; *DNA Methylation ; DNA-Binding Proteins/metabolism ; Dinucleoside Phosphates ; Enhancer Elements, Genetic ; Fathers ; Female ; *Gene Silencing ; *Genomic Imprinting ; Humans ; Insulin-Like Growth Factor II/genetics ; Male ; Models, Genetic ; Mothers ; Muscle Proteins/genetics ; Ovum/metabolism ; Promoter Regions, Genetic ; RNA, Long Noncoding ; *RNA, Untranslated ; Regulatory Sequences, Nucleic Acid ; *Repressor Proteins ; Spermatozoa/metabolism ; Transcription Factors/metabolism ; Zinc Fingers
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-10
    Description: A Drosophila model for Huntington's and other polyglutamine diseases was used to screen for genetic factors modifying the degeneration caused by expression of polyglutamine in the eye. Among 7000 P-element insertions, several suppressor strains were isolated, two of which led to the discovery of the suppressor genes described here. The predicted product of one, dHDJ1, is homologous to human heat shock protein 40/HDJ1. That of the second, dTPR2, is homologous to the human tetratricopeptide repeat protein 2. Each of these molecules contains a chaperone-related J domain. Their suppression of polyglutamine toxicity was verified in transgenic flies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kazemi-Esfarjani, P -- Benzer, S -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1837-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. parsa@its.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710314" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Cloning, Molecular ; Crosses, Genetic ; DNA Transposable Elements ; Disease Models, Animal ; *Drosophila Proteins ; Drosophila melanogaster/anatomy & histology/embryology/*genetics/metabolism ; Expressed Sequence Tags ; Eye/metabolism ; Eye Abnormalities ; Female ; Genes, Insect ; *Genes, Suppressor ; HSP40 Heat-Shock Proteins ; Heat-Shock Proteins/chemistry/*genetics/physiology ; Male ; Molecular Sequence Data ; *Nerve Degeneration ; Neurodegenerative Diseases ; Peptides/genetics/*metabolism ; Phenotype ; Proteins/chemistry ; Repetitive Sequences, Nucleic Acid ; Retina/metabolism ; Suppression, Genetic
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-23
    Description: Multicellular organisms use the products of highly polymorphic genes to distinguish self from conspecific nonself cells or tissues. These allorecognition polymorphisms may regulate somatic interactions between hosts and pathogens or between competitors (to avoid various forms of parasitism), as well as reproductive interactions between mates or between gametes (to avoid inbreeding). In both cases, rare alleles may be advantageous, but it remains unclear which mechanism maintains the genetic polymorphism for specificity in self/nonself recognition. Contrary to earlier reports, we show that mate selection cannot be a strong force maintaining allorecognition polymorphism in two colonial marine invertebrates. Instead, the regulation of intraspecific competitive interactions appears to promote the evolution of polymorphisms in these species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grosberg, R K -- Hart, M W -- New York, N.Y. -- Science. 2000 Sep 22;289(5487):2111-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Evolution and Ecology and Center for Population Biology, One Shields Drive, University of California, Davis, CA 95616, USA. rkgrosberg@ucdavis.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11000110" target="_blank"〉PubMed〈/a〉
    Keywords: *Alleles ; Animals ; Biological Evolution ; Cnidaria/*genetics/physiology ; Crosses, Genetic ; Female ; Genes ; Genotype ; Major Histocompatibility Complex ; Male ; *Polymorphism, Genetic ; *Sexual Behavior, Animal ; Urochordata/*genetics/physiology
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balter, M -- Gibbons, A -- New York, N.Y. -- Science. 2000 May 12;288(5468):948-50.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10841709" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Animals ; Asia ; Emigration and Immigration ; Europe ; Female ; *Fossils ; Geologic Sediments ; Georgia (Republic) ; History, Ancient ; *Hominidae/anatomy & histology/classification ; Humans ; Male ; Paleodontology ; Skull/*anatomy & histology
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  • 40
    Publication Date: 2000-08-05
    Description: The circadian oscillator of the cyanobacterium Synechococcus elongatus, like those in eukaryotes, is entrained by environmental cues. Inactivation of the gene cikA (circadian input kinase) shortens the circadian period of gene expression rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The CikA protein sequence reveals that it is a divergent bacteriophytochrome with characteristic histidine protein kinase motifs and a cryptic response regulator motif. CikA is likely a key component of a pathway that provides environmental input to the circadian oscillator in S. elongatus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmitz, O -- Katayama, M -- Williams, S B -- Kondo, T -- Golden, S S -- GM37040/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):765-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Texas A&M University, College Station, TX 77843-3258, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10926536" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Amino Acid Motifs ; Amino Acid Sequence ; *Bacterial Proteins ; *Biological Clocks/genetics/physiology ; *Circadian Rhythm/genetics/physiology ; Cyanobacteria/genetics/*physiology ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genes, Reporter ; Luminescent Measurements ; Molecular Sequence Data ; Mutation ; Phenotype ; Protein Kinases/chemistry/*genetics/physiology ; Sequence Alignment
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  • 41
    Publication Date: 2000-08-26
    Description: Polyadenylate [poly(A)] polymerase (PAP) catalyzes the addition of a polyadenosine tail to almost all eukaryotic messenger RNAs (mRNAs). The crystal structure of the PAP from Saccharomyces cerevisiae (Pap1) has been solved to 2.6 angstroms, both alone and in complex with 3'-deoxyadenosine triphosphate (3'-dATP). Like other nucleic acid polymerases, Pap1 is composed of three domains that encircle the active site. The arrangement of these domains, however, is quite different from that seen in polymerases that use a template to select and position their incoming nucleotides. The first two domains are functionally analogous to polymerase palm and fingers domains. The third domain is attached to the fingers domain and is known to interact with the single-stranded RNA primer. In the nucleotide complex, two molecules of 3'-dATP are bound to Pap1. One occupies the position of the incoming base, prior to its addition to the mRNA chain. The other is believed to occupy the position of the 3' end of the mRNA primer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bard, J -- Zhelkovsky, A M -- Helmling, S -- Earnest, T N -- Moore, C L -- Bohm, A -- R01 GM57218-01A2/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 25;289(5483):1346-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10958780" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Deoxyadenine Nucleotides/*chemistry/*metabolism ; Hydrogen Bonding ; Manganese/metabolism ; Models, Molecular ; Mutation ; Polynucleotide Adenylyltransferase/*chemistry/genetics/*metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA/metabolism ; RNA, Messenger/metabolism ; Ribosomal Protein S6 ; Ribosomal Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology
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  • 42
    Publication Date: 2000-11-25
    Description: The endoplasmic reticulum (ER) supports disulfide bond formation by a poorly understood mechanism requiring protein disulfide isomerase (PDI) and ERO1. In yeast, Ero1p-mediated oxidative folding was shown to depend on cellular flavin adenine dinucleotide (FAD) levels but not on ubiquinone or heme, and Ero1p was shown to be a FAD-binding protein. We reconstituted efficient oxidative folding in vitro using FAD, PDI, and Ero1p. Disulfide formation proceeded by direct delivery of oxidizing equivalents from Ero1p to folding substrates via PDI. This kinetic shuttling of oxidizing equivalents could allow the ER to support rapid disulfide formation while maintaining the ability to reduce and rearrange incorrect disulfide bonds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tu, B P -- Ho-Schleyer, S C -- Travers, K J -- Weissman, J S -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1571-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090354" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Carboxypeptidases/chemistry/metabolism ; Cathepsin A ; Chemistry, Physical ; Disulfides/chemistry ; Endoplasmic Reticulum/*metabolism ; Flavin-Adenine Dinucleotide/*metabolism ; Glutathione/metabolism ; Glycoproteins/*metabolism ; Microsomes/metabolism ; Mutation ; Oxidation-Reduction ; Oxidoreductases Acting on Sulfur Group Donors ; Physicochemical Phenomena ; Protein Disulfide-Isomerases/genetics/*metabolism ; *Protein Folding ; Ribonuclease, Pancreatic/chemistry/metabolism ; Saccharomyces cerevisiae/metabolism ; *Saccharomyces cerevisiae Proteins
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barinaga, M -- New York, N.Y. -- Science. 2000 May 12;288(5468):943-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10841707" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; Biological Clocks/genetics/*physiology ; CLOCK Proteins ; Cell Cycle Proteins ; Cell Nucleus/metabolism ; Circadian Rhythm/genetics/*physiology ; Cryptochromes ; Drosophila/metabolism ; *Drosophila Proteins ; *Eye Proteins ; Feedback ; Flavoproteins/genetics/*metabolism ; *Gene Expression Regulation ; Mice ; Mutation ; Nuclear Proteins/genetics/*metabolism ; Period Circadian Proteins ; *Photoreceptor Cells, Invertebrate ; Receptors, G-Protein-Coupled ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/*metabolism
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-05-08
    Description: The telomerase ribonucleoprotein has a phylogenetically divergent RNA subunit, which contains a short template for telomeric DNA synthesis. To understand how telomerase RNA participates in mechanistic aspects of telomere synthesis, we studied a conserved secondary structure adjacent to the template. Disruption of this structure caused DNA synthesis to proceed beyond the normal template boundary, resulting in altered telomere sequences, telomere shortening, and cellular growth defects. Compensatory mutations restored normal telomerase function. Thus, the RNA structure, rather than its sequence, specifies the template boundary. This study reveals a specific function for an RNA structure in the enzymatic action of telomerase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tzfati, Y -- Fulton, T B -- Roy, J -- Blackburn, E H -- GM26259/GM/NIGMS NIH HHS/ -- T32CA09270/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 May 5;288(5467):863-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-0414, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10797010" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Cloning, Molecular ; DNA, Fungal/biosynthesis ; Genes, Fungal ; Kluyveromyces/*enzymology/genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; RNA, Fungal/*chemistry/genetics/*metabolism ; Telomerase/*chemistry/genetics/*metabolism ; Telomere/genetics/metabolism ; Templates, Genetic
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-11-10
    Description: The behavioral and ecological factors involved in immune system evolution remain poorly explored. We present a phylogenetic analysis of white blood cell counts in primates to test three hypotheses related to disease risk: increases in risk are expected with group size or population density, exposure to soil-borne pathogens, and mating promiscuity. White blood cell counts were significantly greater in species where females have more mating partners, indicating that the risk of sexually transmitted disease is likely to be a major factor leading to systematic differences in the primate immune system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nunn, C L -- Gittleman, J L -- Antonovics, J -- GM60766-01/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 10;290(5494):1168-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Gilmer Hall, University of Virginia, Charlottesville, VA 22904-4328, USA. charlie.nunn@virginia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11073457" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Zoo ; Biological Evolution ; Body Weight ; Female ; Haplorhini/blood/*immunology ; Immune System/*physiology ; *Leukocyte Count ; Male ; Population Density ; Primate Diseases/epidemiology/immunology ; Risk Factors ; *Sexual Behavior, Animal ; Sexually Transmitted Diseases/epidemiology/immunology/veterinary ; Species Specificity
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-21
    Description: We describe a single RNA sequence that can assume either of two ribozyme folds and catalyze the two respective reactions. The two ribozyme folds share no evolutionary history and are completely different, with no base pairs (and probably no hydrogen bonds) in common. Minor variants of this sequence are highly active for one or the other reaction, and can be accessed from prototype ribozymes through a series of neutral mutations. Thus, in the course of evolution, new RNA folds could arise from preexisting folds, without the need to carry inactive intermediate sequences. This raises the possibility that biological RNAs having no structural or functional similarity might share a common ancestry. Furthermore, functional and structural divergence might, in some cases, precede rather than follow gene duplication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schultes, E A -- Bartel, D P -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):448-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10903205" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Catalysis ; Evolution, Molecular ; Gene Duplication ; Hepatitis Delta Virus/enzymology/genetics ; Molecular Sequence Data ; Mutation ; Nucleic Acid Conformation ; Point Mutation ; RNA/metabolism ; RNA, Catalytic/*chemistry/genetics/*metabolism
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  • 47
    Publication Date: 2000-11-10
    Description: Reciprocal gene activation and restriction during cell type differentiation from a common lineage is a hallmark of mammalian organogenesis. A key question, then, is whether a critical transcriptional activator of cell type-specific gene targets can also restrict expression of the same genes in other cell types. Here, we show that whereas the pituitary-specific POU domain factor Pit-1 activates growth hormone gene expression in one cell type, the somatotrope, it restricts its expression from a second cell type, the lactotrope. This distinction depends on a two-base pair spacing in accommodation of the bipartite POU domains on a conserved growth hormone promoter site. The allosteric effect on Pit-1, in combination with other DNA binding factors, results in the recruitment of a corepressor complex, including nuclear receptor corepressor N-CoR, which, unexpectedly, is required for active long-term repression of the growth hormone gene in lactotropes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scully, K M -- Jacobson, E M -- Jepsen, K -- Lunyak, V -- Viadiu, H -- Carriere, C -- Rose, D W -- Hooshmand, F -- Aggarwal, A K -- Rosenfeld, M G -- R01 DK18477/DK/NIDDK NIH HHS/ -- R01 DK54802/DK/NIDDK NIH HHS/ -- R01 GM49327/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Nov 10;290(5494):1127-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Endocrinology and Metabolism, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11073444" target="_blank"〉PubMed〈/a〉
    Keywords: Allosteric Regulation ; Animals ; Base Sequence ; Binding Sites ; Cell Line ; Conserved Sequence ; Crystallization ; DNA/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Female ; *Gene Expression Regulation ; Genes, Reporter ; Growth Hormone/*genetics ; Male ; Mice ; Mice, Transgenic ; Models, Molecular ; Molecular Sequence Data ; Nuclear Proteins/genetics/metabolism ; Nuclear Receptor Co-Repressor 1 ; Pituitary Gland/cytology/*metabolism ; Prolactin/*genetics ; Promoter Regions, Genetic ; Protein Conformation ; Protein Structure, Tertiary ; Rats ; Repressor Proteins/chemistry/genetics/*metabolism ; Transcription Factor Pit-1 ; Transcription Factors/chemistry/genetics/*metabolism ; Transcriptional Activation
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-10-29
    Description: Songbirds learn a correspondence between vocal-motor output and auditory feedback during development. For neurons in a motor cortex analog of adult zebra finches, we show that the timing and structure of activity elicited by the playback of song during sleep matches activity during daytime singing. The motor activity leads syllables, and the matching sensory response depends on a sequence of typically up to three of the preceding syllables. Thus, sensorimotor correspondence is reflected in temporally precise activity patterns of single neurons that use long sensory memories to predict syllable sequences. Additionally, "spontaneous" activity of these neurons during sleep matches their sensorimotor activity, a form of song "replay." These data suggest a model whereby sensorimotor correspondences are stored during singing but do not modify behavior, and off-line comparison (e.g., during sleep) of rehearsed motor output and predicted sensory feedback is used to adaptively shape motor output.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dave, A S -- Margoliash, D -- MH11615/MH/NIMH NIH HHS/ -- MH59831/MH/NIMH NIH HHS/ -- MH60276/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2000 Oct 27;290(5492):812-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Organismal Biology and Anatomy, University of Chicago, 1027 East 57 Street, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11052946" target="_blank"〉PubMed〈/a〉
    Keywords: *Acoustic Stimulation ; Action Potentials ; Animals ; Feedback ; Learning/*physiology ; Male ; Motor Neurons/physiology ; Neurons/*physiology ; Neurons, Afferent/physiology ; Prosencephalon/*physiology ; Sleep/physiology ; Songbirds/*physiology ; Vocalization, Animal/*physiology
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  • 49
    Publication Date: 2000-02-11
    Description: DARPP-32, a dopamine- and adenosine 3',5'-monophosphate (cAMP)-regulated phosphoprotein (32 kilodaltons in size), is an obligate intermediate in progesterone (P)-facilitated sexual receptivity in female rats and mice. The facilitative effect of P on sexual receptivity in female rats was blocked by antisense oligonucleotides to DARPP-32. Homozygous mice carrying a null mutation for the DARPP-32 gene exhibited minimal levels of P-facilitated sexual receptivity when compared to their wild-type littermates. P significantly increased hypothalamic cAMP levels and cAMP-dependent protein kinase activity. These increases were not inhibited by a D1 subclass dopamine receptor antagonist. P also enhanced phosphorylation of DARPP-32 on threonine 34 in the hypothalamus of mice. DARPP-32 activation is thus an obligatory step in progestin receptor regulation of sexual receptivity in rats and mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, S K -- Fienberg, A A -- O'Callaghan, J P -- Snyder, G L -- Allen, P B -- Dash, P K -- Moore, A N -- Mitchell, A J -- Bibb, J -- Greengard, P -- O'Malley, B W -- MH49662/MH/NIMH NIH HHS/ -- MH57442/MH/NIMH NIH HHS/ -- NS 35457/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1053-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. smani@bcm.tmc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669419" target="_blank"〉PubMed〈/a〉
    Keywords: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology ; Animals ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dopamine/pharmacology ; Dopamine Agonists/pharmacology ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Female ; Hypothalamus/metabolism ; Injections, Intraventricular ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Nerve Tissue Proteins ; Oligonucleotides, Antisense/pharmacology ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Posture ; Progesterone/*pharmacology ; Proteins/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Progesterone/metabolism ; Serotonin/pharmacology ; Sexual Behavior, Animal/*drug effects ; Signal Transduction
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  • 50
    Publication Date: 2000-05-20
    Description: The lungs of cystic fibrosis (CF) patients are chronically infected for years by one or a few lineages of Pseudomonas aeruginosa. These bacterial populations adapt to the highly compartmentalized and anatomically deteriorating lung environment of CF patients, as well as to the challenges of the immune defenses and antibiotic therapy. These selective conditions are precisely those that recent theoretical studies predict for the evolution of mechanisms that augment the rate of variation. Determination of spontaneous mutation rates in 128 P. aeruginosa isolates from 30 CF patients revealed that 36% of the patients were colonized by a hypermutable (mutator) strain that persisted for years in most patients. Mutator strains were not found in 75 non-CF patients acutely infected with P. aeruginosa. This investigation also reveals a link between high mutation rates in vivo and the evolution of antibiotic resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oliver, A -- Canton, R -- Campo, P -- Baquero, F -- Blazquez, J -- New York, N.Y. -- Science. 2000 May 19;288(5469):1251-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Unit for Cystic Fibrosis, Hospital Ramon y Cajal, National Institute of Health (INSALUD), 28034 Madrid, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10818002" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics/radiation effects ; Bronchi/microbiology/pathology ; Chronic Disease ; Cystic Fibrosis/epidemiology/genetics/*microbiology ; Drug Resistance, Microbial ; Genetic Variation ; Humans ; *Mutation ; Phenotype ; Pseudomonas Infections/epidemiology/genetics/*microbiology ; Pseudomonas aeruginosa/drug effects/*genetics/isolation & purification/radiation ; effects ; Random Amplified Polymorphic DNA Technique ; Spain/epidemiology
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  • 51
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marean, C W -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2174-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anthropology, State University of New York, Stony Brook, NY 11794, USA. curtis.marean@sunysb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10744540" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animal Husbandry/*history ; Animals ; *Animals, Domestic/anatomy & histology/physiology ; Archaeology ; Female ; *Goats/anatomy & histology/physiology ; History, Ancient ; Humans ; Iran ; Iraq ; Male ; Sex Characteristics ; Sheep/anatomy & histology/physiology
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-15
    Description: Working out how organs form during embryonic development is a fascinating area of research. In a witty Perspective, Jeff Hardin describes new findings (Nishiwaki et al.) that reveal the many intricate steps needed for gonads to form in the worm C. elegans. Two key players, GON-1 and MIG-17, are metalloproteases that may help migration of distal tip cells by degrading extracellular matrix components.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hardin, J -- New York, N.Y. -- Science. 2000 Jun 23;288(5474):2142-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology and Program in Cellular and Molecular Biology, University of Wisconsin, 1117 West Johnson Street, Madison, WI 53706, USA. jdhardin@facstaff.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10896589" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/cytology/*enzymology/genetics/growth & development ; *Caenorhabditis elegans Proteins ; Cell Movement ; Disintegrins/chemistry/genetics/*metabolism ; Extracellular Matrix/*metabolism ; Gene Expression Regulation, Developmental ; Genes, Helminth ; Gonads/cytology/growth & development/metabolism ; Larva/cytology/enzymology/growth & development ; Metalloendopeptidases/chemistry/genetics/*metabolism ; Morphogenesis ; Muscles/cytology/enzymology ; Mutation
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-02-26
    Description: Spider flagelliform silk is one of the most elastic natural materials known. Extensive sequencing of spider silk genes has shown that the exons and introns of the flagelliform gene underwent intragenic concerted evolution. The intron sequences are more homogenized within a species than are the exons. This pattern can be explained by extreme mutation and recombination pressures on the internally repetitive exons. The iterated sequences within exons encode protein structures that are critical to the function of silks. Therefore, attributes that make silks exceptional biomaterials may also hinder the fixation of optimally adapted protein sequences.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, C Y -- Lewis, R V -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1477-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Wyoming, Laramie, WY 82071-3944, USA. hayashi@uwyo.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10688794" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Crossing Over, Genetic ; DNA/genetics ; DNA Replication ; *Evolution, Molecular ; *Exons ; Gene Conversion ; *Genes ; *Introns ; Molecular Sequence Data ; Mutation ; Proteins/chemistry/*genetics ; Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Selection, Genetic ; Species Specificity ; Spiders/*genetics
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  • 54
    Publication Date: 2000-01-05
    Description: Mutations in copper, zinc superoxide dismutase (SOD) have been implicated in the selective death of motor neurons in 2 percent of amyotrophic lateral sclerosis (ALS) patients. The loss of zinc from either wild-type or ALS-mutant SODs was sufficient to induce apoptosis in cultured motor neurons. Toxicity required that copper be bound to SOD and depended on endogenous production of nitric oxide. When replete with zinc, neither ALS-mutant nor wild-type copper, zinc SODs were toxic, and both protected motor neurons from trophic factor withdrawal. Thus, zinc-deficient SOD may participate in both sporadic and familial ALS by an oxidative mechanism involving nitric oxide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Estevez, A G -- Crow, J P -- Sampson, J B -- Reiter, C -- Zhuang, Y -- Richardson, G J -- Tarpey, M M -- Barbeito, L -- Beckman, J S -- R01 HL58209/HL/NHLBI NIH HHS/ -- R01 NS33291/NS/NINDS NIH HHS/ -- R01 NS36761/NS/NINDS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2498-500.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617463" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/drug therapy/*enzymology/genetics/pathology ; Animals ; *Apoptosis ; Brain-Derived Neurotrophic Factor/pharmacology ; Cells, Cultured ; Chelating Agents/pharmacology ; Copper/metabolism ; Fluoresceins/metabolism ; Liposomes ; Motor Neurons/*cytology/metabolism ; Mutation ; Nitrates/metabolism ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/metabolism ; Nitric Oxide Synthase Type I ; Oxidation-Reduction ; Rats ; Superoxide Dismutase/chemistry/genetics/*metabolism/toxicity ; Superoxides/metabolism ; Zinc/*metabolism
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  • 55
    Publication Date: 2000-01-05
    Description: The hCHK2 gene encodes the human homolog of the yeast Cds1 and Rad53 G2 checkpoint kinases, whose activation in response to DNA damage prevents cellular entry into mitosis. Here, it is shown that heterozygous germ line mutations in hCHK2 occur in Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in the TP53 gene. These observations suggest that hCHK2 is a tumor suppressor gene conferring predisposition to sarcoma, breast cancer, and brain tumors, and they also provide a link between the central role of p53 inactivation in human cancer and the well-defined G2 checkpoint in yeast.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bell, D W -- Varley, J M -- Szydlo, T E -- Kang, D H -- Wahrer, D C -- Shannon, K E -- Lubratovich, M -- Verselis, S J -- Isselbacher, K J -- Fraumeni, J F -- Birch, J M -- Li, F P -- Garber, J E -- Haber, D A -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital Center for Cancer Risk Analysis and Harvard Medical School, Building 149, Charlestown, MA 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617473" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Apoptosis ; Brain Neoplasms/genetics ; Breast Neoplasms/genetics ; Checkpoint Kinase 2 ; Female ; G1 Phase ; *G2 Phase ; *Genes, Tumor Suppressor ; Genes, p53 ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome/enzymology/*genetics/pathology ; Male ; Pedigree ; Polymorphism, Genetic ; Protein Kinases/genetics ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Sarcoma/genetics ; Signal Transduction ; Tumor Cells, Cultured
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-05
    Description: How does imitation occur? How can the motor plans necessary for imitating an action derive from the observation of that action? Imitation may be based on a mechanism directly matching the observed action onto an internal motor representation of that action ("direct matching hypothesis"). To test this hypothesis, normal human participants were asked to observe and imitate a finger movement and to perform the same movement after spatial or symbolic cues. Brain activity was measured with functional magnetic resonance imaging. If the direct matching hypothesis is correct, there should be areas that become active during finger movement, regardless of how it is evoked, and their activation should increase when the same movement is elicited by the observation of an identical movement made by another individual. Two areas with these properties were found in the left inferior frontal cortex (opercular region) and the rostral-most region of the right superior parietal lobule.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iacoboni, M -- Woods, R P -- Brass, M -- Bekkering, H -- Mazziotta, J C -- Rizzolatti, G -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2526-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Mapping Center, Neuropsychiatric Institute, Department of Psychiatry, UCLA School of Medicine, Los Angeles, CA 90095-7085, USA. iacoboni@loni.ucla.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617472" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Brain Mapping ; Cues ; Female ; Fingers/physiology ; Frontal Lobe/*physiology ; Humans ; Imitative Behavior/*physiology ; Magnetic Resonance Imaging ; Male ; Movement ; Neurons/physiology ; Parietal Lobe/*physiology
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, E -- New York, N.Y. -- Science. 1999 Dec 17;286(5448):2244-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636774" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviruses, Human/*genetics ; Adolescent ; Advisory Committees ; *Clinical Trials as Topic ; Fatal Outcome ; Genetic Therapy/*adverse effects ; Genetic Vectors/*adverse effects ; Humans ; Male ; National Institutes of Health (U.S.) ; Ornithine Carbamoyltransferase/genetics ; Ornithine Carbamoyltransferase Deficiency Disease/*therapy ; *Research Subjects ; United States
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  • 58
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, E -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2431.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636794" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/chemistry/*pharmacology/therapeutic use ; Cell Division/drug effects ; DNA/metabolism ; Genes, p53 ; Humans ; Mice ; Mutation ; Neoplasms, Experimental/drug therapy/pathology ; *Protein Folding ; Pyrimidines/chemistry/*pharmacology ; Tumor Suppressor Protein p53/*chemistry/genetics/*metabolism
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Resznick, D N -- Ghalambor, C -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2458-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, Riverside, CA 92521, USA. david.reznick@ucr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636809" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging/genetics ; Animals ; *Biological Evolution ; Drosophila/genetics/physiology ; Female ; *Longevity/genetics ; Male ; *Reproduction/genetics ; Selection, Genetic
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tonks, N K -- Myers, M P -- New York, N.Y. -- Science. 1999 Dec 10;286(5447):2096-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. tonks@cshl.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10617421" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Cell Membrane/metabolism ; Crystallography, X-Ray ; *Genes, Tumor Suppressor ; Humans ; Hydrogen Bonding ; Membrane Lipids/metabolism ; Models, Biological ; Mutation ; Neoplasms/*etiology/genetics ; PTEN Phosphohydrolase ; Phosphatidylinositol 3-Kinases/chemistry/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Phosphoric Monoester Hydrolases/*chemistry/genetics/*metabolism ; Phosphorylation ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Signal Transduction ; *Tumor Suppressor Proteins
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2437.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636799" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; Cell Cycle ; Cell Line ; *Cloning, Organism ; Embryo, Mammalian/*cytology ; *Mice/embryology/genetics ; Mice, Knockout ; Mice, Mutant Strains ; Mutation ; Nuclear Transfer Techniques ; Stem Cells/*cytology/physiology
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  • 62
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hagmann, M -- New York, N.Y. -- Science. 1999 Dec 24;286(5449):2433-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10636795" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Cycle ; Checkpoint Kinase 2 ; Genes, Tumor Suppressor ; Genes, p53 ; Humans ; Li-Fraumeni Syndrome/enzymology/*genetics/pathology ; Mutation ; Phosphorylation ; *Protein Kinases ; Protein-Serine-Threonine Kinases/*genetics/metabolism ; Signal Transduction ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/genetics/metabolism
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-06
    Description: All animal cells have a polarity, that is, different proteins are clustered in distinct domains of the plasma membrane and these regions carry out different jobs. As Peifer discusses in a lively Perspective, new work (Bilder et al.) identifies some of the molecular characters that direct proteins to their different cellular destinations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peifer, M -- New York, N.Y. -- Science. 2000 Jul 7;289(5476):67-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA. peifer@unc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10928931" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Transport ; *Cell Division ; Cell Membrane/metabolism ; *Cell Polarity ; Cell Transformation, Neoplastic ; Cytoplasm/metabolism ; Drosophila/cytology/genetics/metabolism ; *Drosophila Proteins ; Epithelial Cells/cytology/metabolism ; Genes, Tumor Suppressor ; Insect Proteins/chemistry/genetics/metabolism ; Intercellular Junctions/metabolism ; Membrane Proteins/chemistry/*metabolism ; Mutation ; Neoplasms/*etiology/metabolism ; Phenotype ; Protein Structure, Tertiary ; *Tumor Suppressor Proteins
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dobson, A -- Lyles, A -- New York, N.Y. -- Science. 2000 May 12;288(5468):985-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, Princeton University, NJ 08544, USA. andy@eno.princeton.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10841720" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Husbandry ; Animals ; Animals, Zoo ; Breeding ; *Conservation of Natural Resources ; Female ; *Ferrets/genetics/physiology ; Founder Effect ; Genetics, Population ; Male ; Northwestern United States ; Predatory Behavior ; Sciuridae ; Southwestern United States
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  • 65
    Publication Date: 2000-09-16
    Description: Double-stranded RNA (dsRNA) inhibits expression of homologous genes by a process involving messenger RNA degradation. To gain insight into the mechanism of degradation, we examined how RNA interference is affected by mutations in the smg genes, which are required for nonsense-mediated decay. For three of six smg genes tested, mutations resulted in animals that were initially silenced by dsRNA but then recovered; wild-type animals remained silenced. The levels of target messenger RNAs were restored during recovery, and RNA editing and degradation of the dsRNA were identical to those of the wild type. We suggest that persistence of RNA interference relies on a subset of smg genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Domeier, M E -- Morse, D P -- Knight, S W -- Portereiko, M -- Bass, B L -- Mango, S E -- 42014/PHS HHS/ -- 5P30CA42014/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Sep 15;289(5486):1928-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Huntsman Cancer Institute Center for Children and Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10988072" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/metabolism ; Alleles ; Animals ; Caenorhabditis elegans/genetics/*metabolism ; *Caenorhabditis elegans Proteins ; Gene Silencing ; Helminth Proteins/genetics/*metabolism ; Mutation ; Myosin Heavy Chains/genetics/metabolism ; Nonmuscle Myosin Type IIB ; Phosphoproteins/genetics/*metabolism ; RNA Stability ; RNA, Double-Stranded/metabolism/pharmacology ; RNA, Helminth/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-19
    Description: Some experts are growing concerned that Ritalin, a stimulant of the central nervous system used to calm a type of fidgety behavior called "attention-deficit hyperactivity disorder" (ADHD), is overused. Most psychiatrists think, however, that stimulants are being underprescribed, because too many cases of ADHD are going untreated. Now, an authoritative study published in this month's Journal of the American Academy of Child and Adolescent Psychiatry shows that Ritalin is being given to many children who don't fit the diagnosis of ADHD, while others who do are not receiving the drug.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marshall, E -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):721.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10950713" target="_blank"〉PubMed〈/a〉
    Keywords: Attention Deficit Disorder with Hyperactivity/*diagnosis/*drug ; therapy/epidemiology ; Central Nervous System Stimulants/*therapeutic use ; Child ; Drug Utilization ; Female ; Humans ; Male ; Methylphenidate/*therapeutic use ; United States/epidemiology
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):22-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10766625" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/therapeutic use ; Anti-HIV Agents/therapeutic use ; Clinical Trials as Topic/*standards ; *Disclosure ; Disease Transmission, Infectious ; *Ethics, Medical ; Female ; HIV Infections/drug therapy/*transmission/*virology ; HIV-1/*physiology ; Humans ; Male ; Moral Obligations ; Publishing ; Research Subjects ; *Sexual Partners ; Uganda ; Viral Load
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-06
    Description: What makes some people big and others small--obviously our genes, but which ones? Working out the complex of genes that control such quantitative traits in animals and plants is one of the big challenges facing geneticists. In his Perspective, Doebley discusses new results that identify the fw2.2 gene as one of the genes determining fruit size in the tomato (Frary et al.).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doebley, J -- New York, N.Y. -- Science. 2000 Jul 7;289(5476):71-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, University of Wisconsin, Madison, WI 53706, USA. jdoebley@facstaff.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10928932" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Cloning, Molecular ; Fruit/growth & development ; *Genes, Plant ; Lycopersicon esculentum/*genetics/growth & development ; Phenotype ; Plant Proteins/chemistry/*genetics/physiology ; *Quantitative Trait, Heritable ; Transformation, Genetic
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-07
    Description: Loss of cell polarity and tissue architecture are characteristics of malignant cancers derived from epithelial tissues. We provide evidence from Drosophila that a group of membrane-associated proteins act in concert to regulate both epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction-localized protein required for polarization of embryonic and, as demonstrated here, imaginal disc and follicular epithelia. We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia, and that scrib also acts as a tumor suppressor. Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. scrib, dlg, and lgl show strong genetic interactions. Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bilder, D -- Li, M -- Perrimon, N -- New York, N.Y. -- Science. 2000 Jul 7;289(5476):113-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. bilder@rascal.med.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10884224" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Membrane/metabolism ; *Cell Polarity ; Cell Transformation, Neoplastic ; Cytoplasm/metabolism ; Drosophila/*cytology/genetics/growth & development ; *Drosophila Proteins ; Embryo, Nonmammalian/cytology ; Epidermis/embryology/metabolism/ultrastructure ; Epithelial Cells/cytology/metabolism ; Female ; Genes, Insect ; *Genes, Tumor Suppressor ; Insect Proteins/genetics/*metabolism ; Intercellular Junctions/metabolism/ultrastructure ; Membrane Proteins/genetics/*metabolism ; Morphogenesis ; Mutation ; Phenotype ; *Tumor Suppressor Proteins
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  • 70
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, G -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1381.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10722378" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*cytology ; Cell Death ; Cell Division ; Male ; Neurons/*cytology/physiology ; Songbirds/anatomy & histology/*physiology ; Vocalization, Animal
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  • 71
    Publication Date: 2000-08-05
    Description: LEAFY (LFY) and APETALA1 (AP1) encode unrelated transcription factors that activate overlapping sets of homeotic genes in Arabidopsis flowers. Sector analysis and targeted expression in transgenic plants were used to study whether LFY and AP1 can participate in cell-cell signaling between and within different layers of the floral meristem. LFY signaled equally well from all layers and had substantial long-range action within layers. Nonautonomous action of LFY was accompanied by movement of the protein to adjacent cells, where it directly activated homeotic target genes. In contrast, AP1 had only limited nonautonomous effects, apparently mediated by downstream genes because activation of early target genes by AP1 was cell-autonomous.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sessions, A -- Yanofsky, M F -- Weigel, D -- New York, N.Y. -- Science. 2000 Aug 4;289(5480):779-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10926540" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/genetics/growth & development/*metabolism ; *Arabidopsis Proteins ; DNA Nucleotidyltransferases/genetics/metabolism ; Gene Expression Regulation, Plant ; Genes, Homeobox ; Genes, Plant ; Homeodomain Proteins/genetics/*metabolism ; MADS Domain Proteins ; Meristem/genetics/metabolism ; Phenotype ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; RNA, Plant/genetics/metabolism ; *Signal Transduction ; Transcription Factors/genetics/*metabolism
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  • 72
    Publication Date: 2000-12-02
    Description: After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III beta-tubulin) and were able to activate the transcription factor cAMP response element-binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brazelton, T R -- Rossi, F M -- Keshet, G I -- Blau, H M -- AG09521/AG/NIA NIH HHS/ -- CA59717/CA/NCI NIH HHS/ -- HD18179/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 1;290(5497):1775-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pharmacology, CCSR 4215, 269 Campus Drive, Stanford University, Stanford, CA 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11099418" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers/analysis ; Bone Marrow Cells/*cytology ; *Bone Marrow Transplantation ; Brain/*cytology ; Cell Differentiation ; Cell Size ; Cyclic AMP Response Element-Binding Protein/metabolism ; Flow Cytometry ; Gene Expression ; Green Fluorescent Proteins ; Luminescent Proteins/analysis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Confocal ; Nerve Tissue Proteins/analysis/genetics ; Neurons/chemistry/*cytology/metabolism ; Olfactory Bulb/cytology ; Phenotype ; Phosphorylation
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: Researchers are increasingly coming to view violence as the end result of multiple risk factors that may include a biological vulnerability that can be brought out or reinforced by social environment. Longitudinal studies are demonstrating that children who become chronically violent adults generally are difficult from early childhood. But just which early risk factors are most powerful, and how they interact, is proving very tough to sort out.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, C -- New York, N.Y. -- Science. 2000 Jul 28;289(5479):580-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939972" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; *Aggression/psychology ; Behavior Therapy ; Central Nervous System/physiology ; Child ; Child, Preschool ; Female ; Genes ; Humans ; Juvenile Delinquency ; Longitudinal Studies ; Male ; Parenting ; Personality Disorders/psychology ; Psychotropic Drugs/therapeutic use ; Risk Factors ; *Social Environment ; *Violence/psychology
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  • 74
    Publication Date: 2000-12-23
    Description: Plasma Abeta42 (amyloid beta42 peptide) is invariably elevated in early-onset familial Alzheimer's disease (AD), and it is also increased in the first-degree relatives of patients with typical late-onset AD (LOAD). To detect LOAD loci that increase Abeta42, we used plasma Abeta42 as a surrogate trait and performed linkage analysis on extended AD pedigrees identified through a LOAD patient with extremely high plasma Abeta. Here, we report linkage to chromosome 10 with a maximal lod score of 3.93 at 81 centimorgans close to D10S1225. Remarkably, linkage to the same region was obtained independently in a genome-wide screen of LOAD sibling pairs. These results provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase Abeta.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ertekin-Taner, N -- Graff-Radford, N -- Younkin, L H -- Eckman, C -- Baker, M -- Adamson, J -- Ronald, J -- Blangero, J -- Hutton, M -- Younkin, S G -- AG06656/AG/NIA NIH HHS/ -- MH59490/MH/NIMH NIH HHS/ -- P50 AG16574/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 22;290(5500):2303-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11125143" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/*blood/*genetics ; Amyloid beta-Peptides/*blood/genetics ; Chromosomes, Human, Pair 10/*genetics ; Female ; *Genetic Linkage ; Genetic Markers ; Genetic Predisposition to Disease ; Humans ; Lod Score ; Male ; Middle Aged ; Pedigree ; Peptide Fragments/*blood/genetics ; Phenotype ; *Quantitative Trait, Heritable
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharp, P A -- Zamore, P D -- New York, N.Y. -- Science. 2000 Mar 31;287(5462):2431-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. sharppa@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10766620" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*genetics ; *Caenorhabditis elegans Proteins ; *DNA Transposable Elements ; Female ; *Gene Expression Regulation ; *Gene Silencing ; Genes, Helminth ; Helminth Proteins/genetics/physiology ; Male ; Mutation ; RNA, Double-Stranded/*genetics ; RNA, Helminth/*genetics/metabolism ; RNA, Messenger/*genetics/metabolism
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-03-10
    Description: Drosophila exhibits a circadian rest-activity cycle, but it is not known whether fly rest constitutes sleep or is mere inactivity. It is shown here that, like mammalian sleep, rest in Drosophila is characterized by an increased arousal threshold and is homeostatically regulated independently of the circadian clock. As in mammals, rest is abundant in young flies, is reduced in older flies, and is modulated by stimulants and hypnotics. Several molecular markers modulated by sleep and waking in mammals are modulated by rest and activity in Drosophila, including cytochrome oxidase C, the endoplasmic reticulum chaperone protein BiP, and enzymes implicated in the catabolism of monoamines. Flies lacking one such enzyme, arylalkylamine N-acetyltransferase, show increased rest after rest deprivation. These results implicate the catabolism of monoamines in the regulation of sleep and waking in the fly and suggest that Drosophila may serve as a model system for the genetic dissection of sleep.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shaw, P J -- Cirelli, C -- Greenspan, R J -- Tononi, G -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1834-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710313" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arylamine N-Acetyltransferase/genetics/metabolism ; Behavior, Animal/drug effects ; Biogenic Monoamines/metabolism ; Caffeine/pharmacology ; Carrier Proteins/genetics/metabolism ; Circadian Rhythm/*physiology ; Cytochrome P-450 Enzyme System/genetics/metabolism ; *Drosophila Proteins ; Drosophila melanogaster/drug effects/genetics/*physiology ; Fatty Acid Synthases/genetics/metabolism ; Female ; Gene Dosage ; Gene Expression Profiling ; Genes, Insect ; HSC70 Heat-Shock Proteins ; *HSP70 Heat-Shock Proteins ; Homeostasis ; Hydroxyzine/pharmacology ; Mutation ; Rest/physiology ; Sleep/drug effects/*physiology ; Transcription, Genetic ; Wakefulness/drug effects/physiology
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  • 77
    Publication Date: 2000-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williamson, T L -- Corson, L B -- Huang, L -- Burlingame, A -- Liu, J -- Bruijn, L I -- Cleveland, D W -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):399.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10798964" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/*enzymology/genetics/pathology ; Animals ; Apoptosis ; Cells, Cultured ; Copper/metabolism ; Humans ; Mice ; Motor Neurons/metabolism/*pathology ; Mutation ; Neurofilament Proteins/metabolism ; Nitrates/metabolism ; Superoxide Dismutase/*genetics/*metabolism ; Yeasts/cytology/metabolism ; Zinc/*metabolism/toxicity
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-01
    Description: Mechanosensory transduction underlies a wide range of senses, including proprioception, touch, balance, and hearing. The pivotal element of these senses is a mechanically gated ion channel that transduces sound, pressure, or movement into changes in excitability of specialized sensory cells. Despite the prevalence of mechanosensory systems, little is known about the molecular nature of the transduction channels. To identify such a channel, we analyzed Drosophila melanogaster mechanoreceptive mutants for defects in mechanosensory physiology. Loss-of-function mutations in the no mechanoreceptor potential C (nompC) gene virtually abolished mechanosensory signaling. nompC encodes a new ion channel that is essential for mechanosensory transduction. As expected for a transduction channel, D. melanogaster NOMPC and a Caenorhabditis elegans homolog were selectively expressed in mechanosensory organs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walker, R G -- Willingham, A T -- Zuker, C S -- 5T32GM08107/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2229-34.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Howard Hughes Medical Institute, University of California, San Diego,CA 92093-0649, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10744543" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Adaptation, Physiological ; Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics/physiology ; Chromosome Mapping ; Cloning, Molecular ; Dendrites/physiology ; *Drosophila Proteins ; Drosophila melanogaster/genetics/*physiology ; Gene Expression Profiling ; Genes, Insect ; Hair Cells, Auditory/physiology ; Insect Proteins/chemistry/genetics/physiology ; Ion Channels/chemistry/*genetics/*physiology ; Mechanoreceptors/*physiology ; Molecular Sequence Data ; Mutation ; Neurons, Afferent/*physiology ; Patch-Clamp Techniques ; Physical Stimulation ; Proprioception ; Sensation/physiology ; Sense Organs/physiology ; Signal Transduction ; Touch ; Transient Receptor Potential Channels
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  • 79
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Helmuth, L -- New York, N.Y. -- Science. 2000 Jun 2;288(5471):1562-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10858128" target="_blank"〉PubMed〈/a〉
    Keywords: *Clinical Trials as Topic ; Female ; Financing, Government ; Humans ; Male ; National Institutes of Health (U.S.) ; Publishing ; *Research Subjects ; Research Support as Topic ; *Sex Characteristics ; United States ; *Women's Health
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  • 80
    Publication Date: 2000-02-05
    Description: The dynamics of multiple Plasmodium infections in asymptomatic children living under intense malaria transmission pressure provide evidence for a density-dependent regulation that transcends species as well as genotype. This regulation, in combination with species- and genotype-specific immune responses, results in nonindependent, sequential episodes of infection with each species.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bruce, M C -- Donnelly, C A -- Alpers, M P -- Galinski, M R -- Barnwell, J W -- Walliker, D -- Day, K P -- AI24710/AI/NIAID NIH HHS/ -- AI37545/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Feb 4;287(5454):845-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for the Epidemiology of Infectious Disease, Department of Zoology, University of Oxford, Oxford, OX1 3FY, UK. marian.bruce@ceid.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10657296" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Animals ; Child ; Child, Preschool ; Female ; Genotype ; Humans ; Malaria/immunology/*parasitology ; Malaria Vaccines ; Male ; Papua New Guinea ; Parasitemia/*parasitology ; Plasmodium/genetics/*physiology ; Plasmodium falciparum/physiology ; Plasmodium malariae/physiology ; Plasmodium vivax/physiology ; Species Specificity
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  • 81
    Publication Date: 2000-07-15
    Description: The spindle checkpoint was characterized in meiosis of budding yeast. In the absence of the checkpoint, the frequency of meiosis I missegregation increased with increasing chromosome length, reaching 19% for the longest chromosome. Meiosis I nondisjunction in spindle checkpoint mutants could be prevented by delaying the onset of anaphase. In a recombination-defective mutant (spo11Delta), the checkpoint delays the biochemical events of anaphase I, suggesting that chromosomes that are attached to microtubules but are not under tension can activate the spindle checkpoint. Spindle checkpoint mutants reduce the accuracy of chromosome segregation in meiosis I much more than that in meiosis II, suggesting that checkpoint defects may contribute to Down syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shonn, M A -- McCarroll, R -- Murray, A W -- New York, N.Y. -- Science. 2000 Jul 14;289(5477):300-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10894778" target="_blank"〉PubMed〈/a〉
    Keywords: Biomechanical Phenomena ; Chromosome Segregation/*physiology ; Chromosomes, Fungal ; Down Syndrome/genetics ; Endodeoxyribonucleases ; Esterases/genetics ; Kinetochores/physiology ; Meiosis/genetics/*physiology ; Mutation ; Nondisjunction, Genetic ; Recombination, Genetic ; Saccharomycetales/genetics/*physiology ; Spindle Apparatus/*physiology ; Spores, Fungal
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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-05-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koenig, R -- New York, N.Y. -- Science. 2000 Apr 21;288(5465):411.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10798966" target="_blank"〉PubMed〈/a〉
    Keywords: Burial/*history ; Facial Bones/anatomy & histology/injuries ; *Famous Persons ; Greece ; History, Ancient ; Humans ; Male ; Mortuary Practice/history ; Paleontology ; Skull/anatomy & histology
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  • 83
    Publication Date: 2000-12-02
    Description: Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing cells of the myeloid and lymphoid lineages, transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mezey, E -- Chandross, K J -- Harta, G -- Maki, R A -- McKercher, S R -- AI30656/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 1;290(5497):1779-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Basic Neuroscience Program, Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. mezey@codon.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11099419" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/analysis ; Biomarkers/analysis ; Bone Marrow Cells/*cytology/physiology ; *Bone Marrow Transplantation ; Brain/*cytology ; Cell Differentiation ; Cell Movement ; Female ; Immunoenzyme Techniques ; Intermediate Filament Proteins/analysis ; Male ; Mice ; Mice, Knockout ; Microscopy, Confocal ; Nerve Tissue Proteins/analysis/immunology ; Nestin ; Neurons/chemistry/*cytology/immunology ; Phosphopyruvate Hydratase/analysis ; *Stem Cell Transplantation ; Stem Cells/chemistry/*cytology ; Y Chromosome
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  • 84
    Publication Date: 2000-07-06
    Description: Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siegel, R M -- Frederiksen, J K -- Zacharias, D A -- Chan, F K -- Johnson, M -- Lynch, D -- Tsien, R Y -- Lenardo, M J -- NS27177/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2354-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875918" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/*chemistry/genetics/*metabolism ; *Apoptosis ; Autoimmune Diseases/physiopathology ; Cell Line ; Cell Membrane/metabolism ; Cross-Linking Reagents ; Fas Ligand Protein ; Humans ; Ligands ; Lymphocytes/cytology ; Lymphoproliferative Disorders/physiopathology ; Macromolecular Substances ; Membrane Glycoproteins/*metabolism ; Mice ; Mutation ; Point Mutation ; Recombinant Fusion Proteins/chemistry/metabolism ; *Signal Transduction ; Succinimides ; Tumor Cells, Cultured
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  • 85
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-10-29
    Description: During meiosis in Saccharomyces cerevisiae, DNA replication occurs 1. 5 to 2 hours before recombination initiates by DNA double-strand break formation. We show that replication and recombination initiation are directly linked. Blocking meiotic replication prevented double-strand break formation in a replication-checkpoint-independent manner, and delaying replication of a chromosome segment specifically delayed break formation in that segment. Consequently, the time between replication and break formation was held constant in all regions. We suggest that double-strand break formation occurs as part of a process initiated by DNA replication, which thus determines when meiotic recombination initiates on a regional rather than a cell-wide basis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Borde, V -- Goldman, A S -- Lichten, M -- New York, N.Y. -- Science. 2000 Oct 27;290(5492):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry, Division of Basic Science, National Cancer Institute, Bethesda, MD 20892-4255, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11052944" target="_blank"〉PubMed〈/a〉
    Keywords: Chromosomes, Fungal/genetics/metabolism ; DNA Repair ; *DNA Replication ; DNA, Fungal/*metabolism ; Genes, Fungal ; *Meiosis ; Mutation ; *Recombination, Genetic ; Saccharomyces cerevisiae/*genetics/metabolism
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  • 86
    Publication Date: 2000-07-21
    Description: Inbred strains of mice are largely used to identify the genetic basis of normal and pathological behaviors. This report demonstrates that a moderate period of food shortage, an ecologically common experience, can reverse or abolish strain differences in behavioral responses to the abused psychostimulant amphetamine. The period of food shortage occurred when the animals were mature and was terminated before the administration of amphetamine. Strain differences in behavior appear highly dependent on environmental experiences. Consequently, to identify biological determinants of behavior, an integrated approach considering the interaction between environmental and genetic factors needs to be used.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cabib, S -- Orsini, C -- Le Moal, M -- Piazza, P V -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):463-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dipartimento di Psicologia, Universita "La Sapienza" via dei Marsi 78, Roma I-00185, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10903209" target="_blank"〉PubMed〈/a〉
    Keywords: Amphetamine/*pharmacology ; Animals ; Behavior, Animal/*drug effects ; Central Nervous System Stimulants/*pharmacology ; Conditioning (Psychology)/drug effects ; *Food Deprivation ; Genes ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Motor Activity/drug effects ; Phenotype ; Species Specificity ; Substance-Related Disorders/*etiology ; Weight Loss
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  • 87
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-10-20
    Description: Natural selection on mate recognition may often contribute to speciation, resulting in reproductive character displacement. Field populations of Drosophila serrata display reproductive character displacement in cuticular hydrocarbons when sympatric with Drosophila birchii. We exposed field sympatric and allopatric populations of D. serrata to experimental sympatry with D. birchii for nine generations. Cuticular hydrocarbons of field allopatric D. serrata populations evolved to resemble the field sympatric populations, whereas field sympatric D. serrata populations remained unchanged. Our experiment indicates that natural selection on mate recognition resulted in the field pattern of reproductive character displacement.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Higgie, M -- Chenoweth, S -- Blows, M W -- New York, N.Y. -- Science. 2000 Oct 20;290(5491):519-21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology and Entomology, University of Queensland, St. Lucia 4072, Australia. MHiggie@zoology.uq.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11039933" target="_blank"〉PubMed〈/a〉
    Keywords: Analysis of Variance ; Animals ; Australia ; *Biological Evolution ; Discriminant Analysis ; Drosophila/chemistry/*genetics/*physiology ; *Ecosystem ; Female ; Genetic Variation ; Hydrocarbons/analysis ; Male ; Pheromones/analysis ; Reproduction ; *Selection, Genetic ; Sexual Behavior, Animal
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  • 88
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rainey, B P -- Moxon, E R -- New York, N.Y. -- Science. 2000 May 19;288(5469):1186-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. prainey@molbiol.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10841739" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Cystic Fibrosis/drug therapy/microbiology ; Drug Resistance, Microbial ; Humans ; Mutation ; Phenotype ; Pseudomonas aeruginosa/drug effects/*genetics/pathogenicity/physiology
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  • 89
    Publication Date: 2000-10-06
    Description: The signal transducers and activators of transcription (STAT) transcription factors become phosphorylated on tyrosine and translocate to the nucleus after stimulation of cells with growth factors or cytokines. We show that the Rac1 guanosine triphosphatase can bind to and regulate STAT3 activity. Dominant negative Rac1 inhibited STAT3 activation by growth factors, whereas activated Rac1 stimulated STAT3 phosphorylation on both tyrosine and serine residues. Moreover, activated Rac1 formed a complex with STAT3 in mammalian cells. Yeast two-hybrid analysis indicated that STAT3 binds directly to active but not inactive Rac1 and that the interaction occurs via the effector domain. Rac1 may serve as an alternate mechanism for targeting STAT3 to tyrosine kinase signaling complexes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Simon, A R -- Vikis, H G -- Stewart, S -- Fanburg, B L -- Cochran, B H -- Guan, K L -- GM-54304/GM/NIGMS NIH HHS/ -- K08-HL-03547/HL/NHLBI NIH HHS/ -- P30-DK34928/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Oct 6;290(5489):144-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pulmonary and Critical Care Division, Tupper Research Institute, New England Medical Center, Boston, MA 02111, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11021801" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; COS Cells ; Cell Line ; Cercopithecus aethiops ; DNA-Binding Proteins/genetics/*metabolism ; Enzyme Activation ; Epidermal Growth Factor/pharmacology ; Gene Expression Regulation ; Genes, Reporter ; Genetic Vectors ; Guanine Nucleotide Exchange Factors/genetics/metabolism ; Humans ; Janus Kinase 2 ; Mutation ; Neoplasm Proteins ; Phosphorylation ; Phosphoserine/metabolism ; Phosphotyrosine/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proteins/genetics/metabolism ; *Proto-Oncogene Proteins ; Rats ; STAT3 Transcription Factor ; Signal Transduction ; Trans-Activators/genetics/*metabolism ; Transfection ; Two-Hybrid System Techniques ; rac1 GTP-Binding Protein/genetics/*metabolism
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  • 90
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-12-09
    Description: Rhodopsin is essential for photoreceptor morphogenesis; photoreceptors lacking rhodopsin degenerate in humans, mice, and Drosophila. Here we report that transgenic expression of a dominant-active Drosophila Rho guanosine triphosphatase, Drac1, rescued photoreceptor morphogenesis in rhodopsin-null mutants; expression of dominant-negative Drac1 resulted in a phenotype similar to that seen in rhodopsin-null mutants. Drac1 was localized in a specialization of the photoreceptor cortical actin cytoskeleton, which was lost in rhodopsin-null mutants. Thus, rhodopsin appears to organize the actin cytoskeleton through Drac1, contributing a structural support essential for photoreceptor morphogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, H Y -- Ready, D F -- EY10306/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 8;290(5498):1978-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11110667" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism/ultrastructure ; Animals ; Animals, Genetically Modified ; Drosophila/genetics/growth & development/metabolism ; *Drosophila Proteins ; Microscopy, Confocal ; Microvilli/metabolism/ultrastructure ; Morphogenesis ; Mutation ; Photoreceptor Cells, Invertebrate/*growth & development/ultrastructure ; Rhodopsin/genetics/*metabolism ; rac GTP-Binding Proteins/*metabolism
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, J -- New York, N.Y. -- Science. 2000 Mar 24;287(5461):2139-41.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10744531" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/*therapeutic use ; Brain Neoplasms/*drug therapy ; Child, Preschool ; Clinical Trials as Topic/*legislation & jurisprudence ; Government ; Humans ; Male ; Medulloblastoma/drug therapy ; Patient Advocacy ; Patient Participation ; Peptides/*therapeutic use ; Politics ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 92
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-07-06
    Description: The end of communism opened up a life of economic uncertainty in the Eastern Bloc. And that, say some social scientists, may be exerting a deadly effect on residents, whose high expectations that their lives would improve were quickly dashed by the bumpy transition to a market economy. Disillusionment led to stress and depression, and depression was a harbinger of death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, R -- New York, N.Y. -- Science. 2000 Jun 9;288(5472):1732-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10877687" target="_blank"〉PubMed〈/a〉
    Keywords: Communism ; Coronary Disease/etiology/*mortality/psychology ; Depression/complications/*epidemiology ; Europe, Eastern ; Female ; Humans ; Life Expectancy ; Male ; *Mortality ; *Political Systems ; Risk Factors ; *Social Change ; Stress, Psychological/complications/*epidemiology
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  • 93
    Publication Date: 2000-02-26
    Description: The Caenorhabditis elegans Bcl-2-like protein CED-9 prevents programmed cell death by antagonizing the Apaf-1-like cell-death activator CED-4. Endogenous CED-9 and CED-4 proteins localized to mitochondria in wild-type embryos, in which most cells survive. By contrast, in embryos in which cells had been induced to die, CED-4 assumed a perinuclear localization. CED-4 translocation induced by the cell-death activator EGL-1 was blocked by a gain-of-function mutation in ced-9 but was not dependent on ced-3 function, suggesting that CED-4 translocation precedes caspase activation and the execution phase of programmed cell death. Thus, a change in the subcellular localization of CED-4 may drive programmed cell death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, F -- Hersh, B M -- Conradt, B -- Zhou, Z -- Riemer, D -- Gruenbaum, Y -- Horvitz, H R -- New York, N.Y. -- Science. 2000 Feb 25;287(5457):1485-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biology, 68-425, 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/10688797" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Animals, Genetically Modified ; *Apoptosis ; Apoptosis Regulatory Proteins ; Caenorhabditis elegans/*cytology/embryology/genetics/*metabolism ; *Caenorhabditis elegans Proteins ; Calcium-Binding Proteins/genetics/*metabolism ; *Caspases ; Cysteine Endopeptidases/genetics/metabolism ; Genes, Helminth ; Helminth Proteins/genetics/*metabolism ; Immunohistochemistry ; Mitochondria/metabolism ; Mutation ; Nuclear Envelope/*metabolism ; Phenotype ; Proto-Oncogene Proteins/genetics/*metabolism ; Proto-Oncogene Proteins c-bcl-2 ; Repressor Proteins/genetics/metabolism
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-04-15
    Description: A variety of molecular chaperones and folding enzymes assist the folding of newly synthesized proteins in the endoplasmic reticulum. Here we investigated why some glycoproteins interact with the molecular chaperone BiP, and others with the calnexin/calreticulin pathway. The folding of Semliki forest virus glycoproteins and influenza hemagglutinin was studied in living cells. The initial choice of chaperone depended on the location of N-linked glycans in the growing nascent chain. Direct interaction with calnexin and calreticulin without prior interaction with BiP occurred if glycans were present within about 50 residues of the protein's NH2-terminus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Molinari, M -- Helenius, A -- New York, N.Y. -- Science. 2000 Apr 14;288(5464):331-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Federal Institute of Technology Zurich (ETHZ), Universitatstrasse 16, CH-8092 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10764645" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; CHO Cells ; Calcium-Binding Proteins/metabolism ; Calnexin ; Calreticulin ; Carrier Proteins/metabolism ; Chemical Precipitation ; Cricetinae ; Dithiothreitol/pharmacology ; Endoplasmic Reticulum/*metabolism ; Glycoproteins/chemistry/*metabolism ; Glycosylation ; *Heat-Shock Proteins ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics/*metabolism ; Molecular Chaperones/*metabolism ; Molecular Weight ; Mutation ; Oxidation-Reduction ; Polysaccharides/chemistry ; Protein Conformation ; *Protein Folding ; Ribonucleoproteins/metabolism ; Semliki forest virus ; Viral Proteins/chemistry/*metabolism
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  • 95
    Publication Date: 2000-12-09
    Description: Diploid yeast cells repeatedly polarize and bud from their poles, probably because of highly stable marks of unknown composition. Here, Rax2, a membrane protein, was shown to behave as such a mark. The Rax2 protein itself was inherited immutably at the cell cortex for multiple generations, and Rax2 was shown to have a half-life exceeding several generations. The persistent inheritance of cortical protein markers would provide a means to couple a cell's history to the future development of a precise morphogenetic form.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, T -- Hiroko, T -- Chaudhuri, A -- Inose, F -- Lord, M -- Tanaka, S -- Chant, J -- Fujita, A -- GM49782/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 8;290(5498):1975-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11110666" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Division ; *Cell Polarity ; Fungal Proteins/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Morphogenesis ; Mutation ; Phenotype ; Recombinant Fusion Proteins/metabolism ; Yeasts/*cytology/genetics/growth & development/metabolism
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-08-12
    Description: Molecules that have similar sequences usually adopt the same structures and have the same functions. In his Perspective, Joyce explains that this is not always the case. In a remarkable study (Schultes and Bartel), an RNA sequence has been designed that can adopt two different structures, each with a different catalytic function. Joyce details how this study sheds light on the evolution of enzymes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Joyce, G F -- New York, N.Y. -- Science. 2000 Jul 21;289(5478):401-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. gjoyce@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10939951" target="_blank"〉PubMed〈/a〉
    Keywords: Base Pairing ; Base Sequence ; Catalysis ; *Evolution, Molecular ; Hepatitis Delta Virus/enzymology/genetics ; Mutation ; Nucleic Acid Conformation ; RNA, Catalytic/*chemistry/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2000-03-10
    Description: Relative quiescence is a defining characteristic of hematopoietic stem cells, while their progeny have dramatic proliferative ability and inexorably move toward terminal differentiation. The quiescence of stem cells has been conjectured to be of critical biologic importance in protecting the stem cell compartment, which we directly assessed using mice engineered to be deficient in the G1 checkpoint regulator, cyclin-dependent kinase inhibitor, p21cip1/waf1 (p21). In the absence of p21, hematopoietic stem cell proliferation and absolute number were increased under normal homeostatic conditions. Exposing the animals to cell cycle-specific myelotoxic injury resulted in premature death due to hematopoietic cell depletion. Further, self-renewal of primitive cells was impaired in serially transplanted bone marrow from p21-/- mice, leading to hematopoietic failure. Therefore, p21 is the molecular switch governing the entry of stem cells into the cell cycle, and in its absence, increased cell cycling leads to stem cell exhaustion. Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, T -- Rodrigues, N -- Shen, H -- Yang, Y -- Dombkowski, D -- Sykes, M -- Scadden, D T -- AI07387/AI/NIAID NIH HHS/ -- DK50234/DK/NIDDK NIH HHS/ -- HL44851/HL/NHLBI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Mar 10;287(5459):1804-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Hematology, AIDS Research Center, Massachusetts General Hospital Cancer Center, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10710306" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimetabolites/pharmacology ; Blood Cell Count ; Bone Marrow Transplantation ; Cell Count ; *Cell Cycle ; Cell Death ; Cell Differentiation ; Cell Division ; Coculture Techniques ; Colony-Forming Units Assay ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/genetics/*physiology ; Female ; Fluorouracil/pharmacology ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology/drug effects/physiology ; Homeostasis ; Male ; Mice ; Mice, Inbred Strains
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 98
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-09-01
    Description: The strength and integrity of our bones depends on maintaining a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. As we age or as a result of disease, this delicate balancing act becomes tipped in favor of osteoclasts so that bone resorption exceeds bone formation, rendering bones brittle and prone to fracture. A better understanding of the biology of osteoclasts and osteoblasts is providing opportunities for developing therapeutics to treat diseases of bone. Drugs that inhibit the formation or activity of osteoclasts are valuable for treating osteoporosis, Paget's disease, and inflammation of bone associated with rheumatoid arthritis or periodontal disease. Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rodan, G A -- Martin, T J -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1508-14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Merck Research Laboratories, West Point, PA 19486, USA. St. Vincent's Institute of Medical Research, Melbourne 3065, Australia. gideon_rodan@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968781" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Diseases/*drug therapy/genetics/physiopathology/therapy ; Bone Resorption/drug therapy ; Calcitonin/therapeutic use ; Diphosphonates/therapeutic use ; Estrogen Receptor Modulators/therapeutic use ; Estrogens/therapeutic use ; Female ; Genetic Therapy ; Growth Substances/therapeutic use ; Humans ; Male ; Osteoclasts/drug effects ; Osteogenesis/drug effects ; Osteoporosis/*drug therapy/genetics/physiopathology/therapy ; Parathyroid Hormone/therapeutic use
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 99
    Publication Date: 2000-12-16
    Description: Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rogina, B -- Reenan, R A -- Nilsen, S P -- Helfand, S L -- AG14532/AG/NIA NIH HHS/ -- AG16667/AG/NIA NIH HHS/ -- R37 AG016667/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2000 Dec 15;290(5499):2137-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Developmental Biology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington CT 06030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11118146" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*genetics ; Amino Acid Sequence ; Animals ; Behavior, Animal ; Biological Transport ; Carrier Proteins/chemistry/*genetics/metabolism ; Crosses, Genetic ; DNA Transposable Elements ; *Dicarboxylic Acid Transporters ; Digestive System/metabolism ; *Drosophila Proteins ; Drosophila melanogaster/*genetics/metabolism/physiology ; Energy Intake ; Energy Metabolism ; Fat Body/metabolism ; Female ; Fertility ; Gene Expression ; *Genes, Insect ; Longevity/*genetics ; Male ; Membrane Proteins/chemistry/metabolism ; Molecular Sequence Data ; Mutagenesis, Insertional ; Mutagenesis, Site-Directed ; *Organic Anion Transporters, Sodium-Dependent ; Sense Organs/cytology/metabolism ; Sequence Homology, Amino Acid ; *Symporters
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  • 100
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-01-29
    Description: Proteins capable of self-perpetuating changes in conformation and function (known as prions) can serve as genetic elements. To test whether novel prions could be created by recombinant methods, a yeast prion determinant was fused to the rat glucocorticoid receptor. The fusion protein existed in different heritable functional states, switched between states at a low spontaneous rate, and could be induced to switch by experimental manipulations. The complete change in phenotype achieved by transferring a prion determinant from one protein to another confirms the protein-only nature of prion inheritance and establishes a mechanism for engineering heritable changes in phenotype that should be broadly applicable.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Lindquist, S -- New York, N.Y. -- Science. 2000 Jan 28;287(5453):661-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 South Maryland Avenue MC1028, Chicago, IL 60637, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10650001" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Fungal Proteins/*chemistry/genetics/*metabolism ; Genes, Reporter ; Guanidine/pharmacology ; Heat-Shock Proteins/pharmacology ; Peptide Termination Factors ; Phenotype ; Prions/*chemistry/genetics/*metabolism ; Rats ; Receptors, Glucocorticoid/chemistry/genetics/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Saccharomyces cerevisiae/chemistry/genetics ; *Saccharomyces cerevisiae Proteins ; Transcription, Genetic ; Transformation, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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