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  • 1
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    Identification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzyme (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉Glycogen is the primary storage form of glucose. Glycogen synthesis and breakdown are tightly controlled by glycogen synthase (GYS) and phosphorylase, respectively. The enzyme responsible for dephosphorylating GYS and phosphorylase, which results in their activation (GYS) or inactivation (phosphorylase) to robustly stimulate glycogen synthesis, is protein phosphatase 1 (PP1). However, our understanding of how PP1 recruits these substrates is limited. Here, we show how PP1, together with its muscle glycogen–targeting (G〈sub〉M〈/sub〉) regulatory subunit, recruits and selectively dephosphorylates its substrates. Our molecular data reveal that the G〈sub〉M〈/sub〉 carbohydrate binding module (G〈sub〉M〈/sub〉〈sup〉CBM21〈/sup〉), which is amino-terminal to the G〈sub〉M〈/sub〉 PP1 binding domain, has a dual function in directing PP1 substrate specificity: It either directly recruits substrates (i.e., GYS) or recruits them indirectly by localization (via glycogen for phosphorylase). Our data provide the molecular basis for PP1 regulation by G〈sub〉M〈/sub〉 and reveal how PP1-mediated dephosphorylation is driven by scaffolding-based substrate recruitment.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Transient episodes of mild environmental oxygenation and oxidative continental weathering during the late Archean (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-11-22
    Description: It is not known whether environmental O 2 levels increased in a linear fashion or fluctuated dynamically between the evolution of oxygenic photosynthesis and the later Great Oxidation Event. New rhenium-osmium isotope data from the late Archean Mount McRae Shale, Western Australia, reveal a transient episode of oxidative continental weathering more than 50 million years before the onset of the Great Oxidation Event. A depositional age of 2495 ± 14 million years and an initial 187 Os/ 188 Os of 0.34 ± 0.19 were obtained for rhenium- and molybdenum-rich black shales. The initial 187 Os/ 188 Os is higher than the mantle/extraterrestrial value of 0.11, pointing to mild environmental oxygenation and oxidative mobilization of rhenium, molybdenum, and radiogenic osmium from the upper continental crust and to contemporaneous transport of these metals to seawater. By contrast, stratigraphically overlying black shales are rhenium- and molybdenum-poor and have a mantle-like initial 187 Os/ 188 Os of 0.06 ± 0.09, indicating a reduced continental flux of rhenium, molybdenum, and osmium to seawater because of a drop in environmental O 2 levels. Transient oxygenation events, like the one captured by the Mount McRae Shale, probably separated intervals of less oxygenated conditions during the late Archean.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Enhanced positive cloud-to-ground lightning in thunderstorms ingesting smoke from fires (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-10-02
    Description: Smoke from forest fires in southern Mexico was advected into the U.S. southern plains from April to June 1998. Cloud-to-ground lightning (CG) flash data from the National Lightning Detection Network matched against satellite-mapped aerosol plumes imply that thunderstorms forming in smoke-contaminated air masses generated large amounts of lightning with positive polarity (+CGs). During 2 months, nearly half a million flashes in the southern plains exhibited +CG percentages that were triple the climatological norm. The peak currents in these +CGs were double the expected value. These thunderstorms also produced abnormally high numbers of mesospheric optical sprites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lyons -- Nelson -- Williams -- Cramer -- Turner -- New York, N.Y. -- Science. 1998 Oct 2;282(5386):77-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉W. A. Lyons and T. E. Nelson, FMA Research Inc., Yucca Ridge Field Station, Fort Collins, CO 80524, USA. E. R. Williams, Parsons Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. J. A. Cramer and T. R. Turner, Glo.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9756479" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Genome maps 10. Comparative genomics. Mammalian radiations. Wall chart (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Brien, S J -- Eisenberg, J F -- Miyamoto, M -- Hedges, S B -- Kumar, S -- Wilson, D E -- Menotti-Raymond, M -- Murphy, W J -- Nash, W G -- Lyons, L A -- Menninger, J C -- Stanyon, R -- Wienberg, J -- Copeland, N G -- Jenkins, N A -- Gellin, J -- Yerle, M -- Andersson, L -- Womack, J -- Broad, T -- Postlethwait, J -- Serov, O -- Bailey, E -- James, M R -- Marshall Graves, J A -- New York, N.Y. -- Science. 1999 Oct 15;286(5439):463-78.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Cancer Institute, Frederick, MD, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10577209" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; *Chromosome Mapping ; Chromosome Painting ; *Genome ; *Genome, Human ; Humans ; Mammals/*genetics ; Nucleic Acid Hybridization ; Phylogeny
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Geomicrobiology of subglacial ice above Lake Vostok, Antarctica (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-12-11
    Description: Data from ice 3590 meters below Vostok Station indicate that the ice was accreted from liquid water associated with Lake Vostok. Microbes were observed at concentrations ranging from 2.8 x 10(3) to 3.6 x 10(4) cells per milliliter; no biological incorporation of selected organic substrates or bicarbonate was detected. Bacterial 16S ribosomal DNA genes revealed low diversity in the gene population. The phylotypes were closely related to extant members of the alpha- and beta-Proteobacteria and the Actinomycetes. Extrapolation of the data from accretion ice to Lake Vostok implies that Lake Vostok may support a microbial population, despite more than 10(6) years of isolation from the atmosphere.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Priscu, J C -- Adams, E E -- Lyons, W B -- Voytek, M A -- Mogk, D W -- Brown, R L -- McKay, C P -- Takacs, C D -- Welch, K A -- Wolf, C F -- Kirshtein, J D -- Avci, R -- New York, N.Y. -- Science. 1999 Dec 10;286(5447):2141-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, Montana State University, Bozeman, MT 59717, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10591642" target="_blank"〉PubMed〈/a〉
    Keywords: Antarctic Regions ; Bacteria/classification/genetics/*isolation & purification ; Bacterial Physiological Phenomena ; DNA, Bacterial/genetics/isolation & purification ; DNA, Ribosomal/genetics/isolation & purification ; Fresh Water/chemistry/*microbiology ; Genes, rRNA ; *Ice ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Minerals/analysis ; Pressure ; Proteobacteria/classification/genetics/isolation & purification/physiology ; RNA, Ribosomal, 16S/genetics ; Temperature ; Water Microbiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Interlocked feedback loops within the Drosophila circadian oscillator (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-10-26
    Description: Drosophila Clock (dClk) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning. dClk mRNA cycling is shown here to be regulated by PERIOD-TIMELESS (PER-TIM)-mediated release of dCLK- and CYCLE (CYC)-dependent repression. Lack of both PER-TIM derepression and dCLK-CYC repression results in high levels of dClk mRNA, which implies that a separate dClk activator is present. These results demonstrate that the Drosophila circadian feedback loop is composed of two interlocked negative feedback loops: a per-tim loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a dClk loop, which is repressed by dCLK-CYC and derepressed by PER-TIM.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glossop, N R -- Lyons, L C -- Hardin, P E -- NS-31214/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Oct 22;286(5440):766-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biochemistry and Biological Clocks Program, University of Houston, Houston, TX 77204-5513, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10531060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Clocks ; CLOCK Proteins ; *Circadian Rhythm ; Dimerization ; Drosophila/*genetics/metabolism ; *Drosophila Proteins ; Feedback ; *Gene Expression Regulation ; Genes, Insect ; Insect Proteins/genetics ; Models, Genetic ; Mutation ; Nuclear Proteins/metabolism ; Period Circadian Proteins ; RNA, Messenger/genetics/metabolism ; Transcription Factors/*genetics/metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Recent origin of Plasmodium falciparum from a single progenitor (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-07-21
    Description: Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts efforts to control disease caused by this parasite. Genetic variation in antigenic, drug resistance, and pathogenesis determinants is abundant, consistent with an ancient origin of P. falciparum, whereas DNA variation at silent (synonymous) sites in coding sequences appears virtually absent, consistent with a recent origin of the parasite. To resolve this paradox, we analyzed introns and demonstrated that these are deficient in single-nucleotide polymorphisms, as are synonymous sites in coding regions. These data establish the recent origin of P. falciparum and further provide an explanation for the abundant diversity observed in antigen and other selected genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Volkman, S K -- Barry, A E -- Lyons, E J -- Nielsen, K M -- Thomas, S M -- Choi, M -- Thakore, S S -- Day, K P -- Wirth, D F -- Hartl, D L -- New York, N.Y. -- Science. 2001 Jul 20;293(5529):482-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Harvard-Oxford Malaria Genome Diversity Project, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11463913" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Agriculture ; Alternative Splicing ; Animals ; Base Sequence ; *Biological Evolution ; Genes, Protozoan ; *Genetic Variation ; Humans ; *Introns ; Malaria, Falciparum/epidemiology/parasitology/transmission ; *Microsatellite Repeats ; Molecular Sequence Data ; Mutation ; Plasmodium/genetics ; Plasmodium falciparum/*genetics ; *Polymorphism, Single Nucleotide
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 8
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    Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-06-20
    Description: The shaker-2 mouse mutation, the homolog of human DFNB3, causes deafness and circling behavior. A bacterial artificial chromosome (BAC) transgene from the shaker-2 critical region corrected the vestibular defects, deafness, and inner ear morphology of shaker-2 mice. An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC. Shaker-2 mice were found to have an amino acid substitution at a highly conserved position within the motor domain of this myosin. Auditory hair cells of shaker-2 mice have very short stereocilia and a long actin-containing protrusion extending from their basal end. This histopathology suggests that Myo15 is necessary for actin organization in the hair cells of the cochlea.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Probst, F J -- Fridell, R A -- Raphael, Y -- Saunders, T L -- Wang, A -- Liang, Y -- Morell, R J -- Touchman, J W -- Lyons, R H -- Noben-Trauth, K -- Friedman, T B -- Camper, S A -- Z01 DC 00035/DC/NIDCD NIH HHS/ -- Z01 DC 00038/DC/NIDCD NIH HHS/ -- Z01 DC 02407/DC/NIDCD NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1998 May 29;280(5368):1444-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, 4701 MSRB III, University of Michigan, 1500 West Medical Center Drive, Ann Arbor, MI 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9603735" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Brain/metabolism ; Chromosomes, Bacterial ; Deafness/*genetics/pathology/therapy ; Ear, Inner/metabolism ; Female ; Genetic Complementation Test ; Hair Cells, Auditory/ultrastructure ; Humans ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mice, Transgenic ; Myosins/chemistry/*genetics/metabolism ; Phenotype ; Point Mutation ; Transgenes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
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    Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-09-28
    Description: Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin α3β1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.
    Keywords: Medicine, Diseases, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Glia as architects of central nervous system formation and function (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-10-12
    Description: Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, and microglia each influence nervous system development, from neuronal birth, migration, axon specification, and growth through circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, and network-level activity through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health, and function.
    Keywords: Neuroscience
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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