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National Toxicology Program (NTP)
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Laboratory of Structural Biology (LSB)
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Laboratory of Molecular Genetics (LMG)
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Publication History View all

  • [Show abstract] [Hide abstract]
    ABSTRACT: Lacrimal glands provide the important function of lubricating and protecting the ocular surface. Failure of proper lacrimal gland function results in a number of debilitating dry eye diseases. Lacrimal glands secrete lipids, mucins, proteins, salts and water and these secretions are at least partially regulated by neurotransmitter-mediated cell signaling. The predominant signaling mechanism for lacrimal secretion involves activation of phospholipase C, generation of the Ca2+-mobilizing messenger, IP3, and release of Ca2+ stored in the endoplasmic reticulum. The loss of Ca2+ from the endoplasmic reticulum then triggers a process known as store-operated Ca2+ entry, involving a Ca2+ sensor in the endoplasmic reticulum, STIM1, which activates plasma membrane store-operated channels comprised of Orai subunits. Recent studies with deletions of the channel subunit, Orai1, confirm the important role of SOCE in both fluid and protein secretion in lacrimal glands, both in vivo and in vitro.
    Cell calcium 06/2014;
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    ABSTRACT: While primordial life is thought to have been RNA-based (Cech, Cold Spring Harbor Perspect. Biol. 4 (2012) a006742), all living organisms store genetic information in DNA, which is chemically more stable. Distinctions between the RNA and DNA worlds and our views of "DNA" synthesis continue to evolve as new details emerge on the incorporation, repair and biological effects of ribonucleotides in DNA genomes of organisms from bacteria through humans.
    DNA repair 04/2014;
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    ABSTRACT: Human mitochondria harbor an essential, high copy number, 16,569 base pair, circular DNA genome that encodes 13 gene products required for electron transport and oxidative phosphorylation. Mutation of this genome can compromise cellular respiration, ultimately resulting in a variety of progressive metabolic diseases collectively known as 'mitochondrial diseases'. Mutagenesis of mtDNA and the persistence of mtDNA mutations in cells and tissues is a complex topic, involving the interplay of DNA replication, DNA damage and repair, purifying selection, organelle dynamics, mitophagy, and aging. We briefly review these general elements that affect maintenance of mtDNA, and we focus on nuclear genes encoding the mtDNA replication machinery that can perturb the genetic integrity of the mitochondrial genome.
    DNA repair 04/2014;


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Top publications last week by downloads

Journal of the American Chemical Society 08/2004; 126(27):8441-53.
Methods in Molecular Biology 02/2002; 197:159-76.

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