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  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (3)
  • Wiley-Blackwell  (2)
  • American Heart Association (AHA)
  • 2010-2014  (5)
  • 2014  (5)
Document type
Years
  • 2010-2014  (5)
Year
  • 1
    Publication Date: 2014-03-15
    Description: Despite being a major health problem, respiratory syncytial virus (RSV) infections remain without specific therapy. Identification of novel host cellular responses that play a role in the pathogenesis of RSV infection is needed for therapeutic development. The endoplasmic reticulum (ER) stress response is an evolutionarily conserved cellular signaling cascade that has been implicated in multiple biological phenomena, including the pathogenesis of some viral infections. In this study, we investigate the role of the ER stress response in RSV infection using an in vitro A549 cell culture model. We found that RSV infection induces a non-canonical ER stress response with preferential activation of the inositol-requiring enzyme 1 (IRE1) and activated transcription factor 6 (ATF6) pathways with no concomitant significant activation of the protein kinase R-like ER kinase (PERK) pathway. Furthermore, we discovered that IRE1 has an inhibitory effect on RSV replication. Our data characterize, for the first time, the nature of the ER stress response in the setting of RSV infection and identify the IRE1 stress pathway as a novel cellular anti-RSV defense mechanism.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 2
    Publication Date: 2014-08-30
    Description: PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). Like Brca1 and Brca2, systemic knock-out of Palb2 in mice results in embryonic lethality. In this study, we generated a hypomorphic Palb2 allele expressing a mutant PALB2 protein unable to bind BRCA1. Consistent with an FA-like phenotype, cells from the mutant mice showed hypersensitivity and chromosomal breakage when treated with mitomycin C, a DNA interstrand crosslinker. Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect. Our results underscore the in vivo importance of the PALB2-BRCA1 complex formation in DSB repair and male meiosis.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 3
    Publication Date: 2014-10-24
    Description: Amateur radio reporting networks, such as the Reverse Beacon Network (RBN), PSKReporter, and the Weak Signal Propagation Network, are powerful tools for remote sensing the ionosphere. These voluntarily constructed and operated networks provide real-time and archival data that could be used for space weather operations, forecasting, and research. The potential exists for the study of both global and localized effects. The capability of one such network to detect space weather disturbances is demonstrated by examining the impacts on RBN-observed HF propagation paths of an X2.9 class solar flare detected by the GOES 15 satellite. Prior to the solar flare, the RBN observed strong HF propagation conditions between multiple continents, primarily Europe, North America, and South America. Immediately following the GOES 15 detection of the solar flare, the number of reported global RBN propagation paths dropped to less than 35% that of prior observations. After the flare, the RBN showed the gradual recovery of HF propagation conditions
    Print ISSN: 1539-4964
    Electronic ISSN: 1542-7390
    Topics: Geosciences , Physics
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  • 4
    Publication Date: 2014-03-14
    Description: Fossil fuel combustion has increased atmospheric CO 2 by ≈ 115 µmol mol -1 since 1750, and decreased its carbon isotope composition (δ 13 C) by 1.7-2 ‰ (the 13 C Suess effect). Because carbon is stored in the terrestrial biosphere for decades and longer, the δ 13 C of CO 2 released by terrestrial ecosystems is expected to differ from the δ 13 C of CO 2 assimilated by land plants during photosynthesis. This isotopic difference between land-atmosphere respiration (δ R ) and photosynthetic assimilation (δ A ) fluxes gives rise to the 13 C land disequilibrium (D). Contemporary understanding suggests that over annual and longer time scales, D is determined primarily by the Suess effect, and thus D is generally positive (δ R  〉 δ A ). A seven-year record of biosphere-atmosphere carbon exchange was used to evaluate the seasonality of δ A and δ R , and the 13 C land disequilibrium, in a subalpine conifer forest. A novel isotopic mixing model was employed to determine the δ 13 C of net land-atmosphere exchange during day and night, and combined with tower-based flux observations to assess δ A and δ R . The disequilibrium varied seasonally, and when flux-weighted was opposite in sign than expected from the Suess effect (D = -0.75 ± 0.21 ‰ or -0.88 ± 0.10 ‰ depending on method). Seasonality in D appeared to be driven by photosynthetic discrimination (Δ canopy ) responding to environmental factors. Possible explanations for negative D include: 1) changes in Δ canopy over decades as CO 2 and temperature have risen, and/or 2) post-photosynthetic fractionation processes leading to sequestration of isotopically-enriched carbon in long-lived pools like wood and soil.
    Print ISSN: 0886-6236
    Electronic ISSN: 1944-9224
    Topics: Biology , Chemistry and Pharmacology , Geography , Geosciences , Physics
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  • 5
    Publication Date: 2014-11-29
    Description: Alzheimer disease (AD) is a progressive neurodegenerative disease leading to memory loss. Numerous lines of evidence suggest that amyloid-β (Aβ), a neurotoxic peptide, initiates a cascade that results in synaptic dysfunction, neuronal death, and eventually cognitive deficits. Aβ is generated by the proteolytic processing of the amyloid precursor protein (APP), and alterations to this processing can result in Alzheimer disease. Using in vitro and in vivo models, we identified cyclopamine as a novel regulator of γ-secretase-mediated cleavage of APP. We demonstrate that cyclopamine decreases Aβ generation by altering APP retrograde trafficking. Specifically, cyclopamine treatment reduced APP-C-terminal fragment (CTF) delivery to the trans-Golgi network where γ-secretase cleavage occurs. Instead, cyclopamine redirects APP-CTFs to the lysosome. These data demonstrate that cyclopamine treatment decreases γ-secretase-mediated cleavage of APP. In addition, cyclopamine treatment decreases the rate of APP-CTF degradation. Together, our data demonstrate that cyclopamine alters APP processing and Aβ generation by inducing changes in APP subcellular trafficking and APP-CTF degradation.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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