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  • 1
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    A PtdIns4,5P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-02-22
    Description: Phosphoinositides are a family of lipid signalling molecules that regulate many cellular functions in eukaryotes. Phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P2), the central component in the phosphoinositide signalling circuitry, is generated primarily by type I phosphatidylinositol 4-phosphate 5-kinases (PIPKIalpha, PIPKIbeta and PIPKIgamma). In addition to functions in the cytosol, phosphoinositides are present in the nucleus, where they modulate several functions; however, the mechanism by which they directly regulate nuclear functions remains unknown. PIPKIs regulate cellular functions through interactions with protein partners, often PtdIns4,5P2 effectors, that target PIPKIs to discrete subcellular compartments, resulting in the spatial and temporal generation of PtdIns4,5P2 required for the regulation of specific signalling pathways. Therefore, to determine roles for nuclear PtdIns4,5P2 we set out to identify proteins that interacted with the nuclear PIPK, PIPKIalpha. Here we show that PIPKIalpha co-localizes at nuclear speckles and interacts with a newly identified non-canonical poly(A) polymerase, which we have termed Star-PAP (nuclear speckle targeted PIPKIalpha regulated-poly(A) polymerase) and that the activity of Star-PAP can be specifically regulated by PtdIns4,5P2. Star-PAP and PIPKIalpha function together in a complex to control the expression of select mRNAs, including the transcript encoding the key cytoprotective enzyme haem oxygenase-1 (refs 8, 9) and other oxidative stress response genes by regulating the 3'-end formation of their mRNAs. Taken together, the data demonstrate a model by which phosphoinositide signalling works in tandem with complement pathways to regulate the activity of Star-PAP and the subsequent biosynthesis of its target mRNA. The results reveal a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellman, David L -- Gonzales, Michael L -- Song, Chunhua -- Barlow, Christy A -- Wang, Ping -- Kendziorski, Christina -- Anderson, Richard A -- R01 GM051968/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Feb 21;451(7181):1013-7. doi: 10.1038/nature06666.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular and Cellular Pharmacology, University of Wisconsin Medical School, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18288197" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Nucleus/enzymology/genetics/*metabolism ; Heme Oxygenase-1/genetics ; Humans ; Mice ; Multiprotein Complexes/metabolism ; Oxidative Stress/genetics ; Phosphatidylinositol 4,5-Diphosphate ; Phosphatidylinositol Phosphates/*metabolism ; Phosphotransferases (Alcohol Group Acceptor)/deficiency/genetics/metabolism ; Polynucleotide Adenylyltransferase/chemistry/deficiency/genetics/*metabolism ; Protein Binding ; *RNA 3' End Processing ; RNA, Messenger/genetics/metabolism ; Substrate Specificity ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Latitudinal variation in glacial erosion rates from Patagonia and the Antarctic Peninsula (46{degrees}S-65{degrees}S) (2016)
    Geological Society of America (GSA)
    Details
    Publication Date: 2016-04-29
    Description: We use extensive sedimentary and marine geophysical data to derive sediment volume–based millennial time-scale glacial erosion rates ( Ē ) from glacially influenced fjords and bays across a broad latitudinal transect, from central Patagonia (46°S) to the Antarctic Peninsula (65°S), and to determine how glacial erosion rates change with increasing latitude and decreasing atmospheric temperatures. We also calculate million-year time-scale erosion rates for the western Antarctic Peninsula cordillera and inner continental shelf from seismic stratigraphic analysis of the continental margin. These results are complemented by erosion rates derived from existing thermochronology data sets (apatite fission-track and apatite [U-Th]/He) for both Patagonia and the Antarctic Peninsula regions. Despite considerable regional variability, our results show a clear trend of decreasing Ē with increasing latitude. Millennial Ē values span two orders of magnitude, from 0.02 mm/yr for Illiad glacier on Anvers Island, Antarctica (~64.5°S), to 0.83 mm/yr for San Rafael glacier in northern Patagonia (~46.5°S). Regional averages are three times higher for the Patagonian areas than the Antarctic Peninsula areas. This trend is interpreted to result from a general decrease in temperature and water availability at the ice-bedrock interface. For the Antarctic Peninsula study sites, erosion rates are highly clustered around 0.1 mm/yr, with the exception of Maxwell Bay, for which the Ē value is 0.36 mm/yr. In Patagonia, erosion rates are more variable than in the Antarctic Peninsula, with Ē ranging between 0.14 mm/yr (Europa glacier area) and 0.83 mm/yr (San Rafael glacier area). This regional variability in Ē is interpreted as due to differences in hypsometry and bedrock resistance to erosion. Million-year time-scale Ē values derived from thermochronology ages also decrease with latitude, with maximum values decreasing from ~0.9–1.1 mm/yr north of 46°S to ~0.1–0.2 mm/yr south of 48°S in Patagonia, and reaching ~0.2–0.3 mm/yr in the Antarctic Peninsula. The sediment-based million-year time-scale Ē estimates for the western Antarctic Peninsula cordillera indicate that glacial erosion rates increased by 25%–30% after 5.3 Ma, from ~0.09 mm/yr (5.3–9.5 Ma) to ~0.11–0.12 mm/yr (〈5.3 Ma). For Patagonia, the decrease in long-term erosion rates south of ~46°S is interpreted to result from relatively long periods of slow glacial erosion associated with the ice masses having been colder (subpolar) on the southern Patagonian cordillera, and having eroded at rates comparable to those we obtained for the Antarctic Peninsula. These long-term erosion rates are 1–2 orders of magnitude lower than estimates based on recent sediment yields, highlighting the transient nature of high-sediment-flux events. However, our sediment volume–derived millennial time-scale Ē closely approximates the maximum values of tectonic time-scale Ē values derived from thermochronology ages. Our combined millennial and million-year time-scale glacial erosion data quantify the significant decrease in rates of glacially driven denudation at geological (tectonic) and millennial time scales with increasing latitude from Patagonia to the Antarctic Peninsula, highlighting the influence of climate on mountain denudation.
    Print ISSN: 0016-7606
    Electronic ISSN: 1943-2674
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 3
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    A compendium of RNA-binding motifs for decoding gene regulation (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-07-13
    Description: RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929597/" 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/PMC3929597/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ray, Debashish -- Kazan, Hilal -- Cook, Kate B -- Weirauch, Matthew T -- Najafabadi, Hamed S -- Li, Xiao -- Gueroussov, Serge -- Albu, Mihai -- Zheng, Hong -- Yang, Ally -- Na, Hong -- Irimia, Manuel -- Matzat, Leah H -- Dale, Ryan K -- Smith, Sarah A -- Yarosh, Christopher A -- Kelly, Seth M -- Nabet, Behnam -- Mecenas, Desirea -- Li, Weimin -- Laishram, Rakesh S -- Qiao, Mei -- Lipshitz, Howard D -- Piano, Fabio -- Corbett, Anita H -- Carstens, Russ P -- Frey, Brendan J -- Anderson, Richard A -- Lynch, Kristen W -- Penalva, Luiz O F -- Lei, Elissa P -- Fraser, Andrew G -- Blencowe, Benjamin J -- Morris, Quaid D -- Hughes, Timothy R -- 1R01HG00570/HG/NHGRI NIH HHS/ -- DK015602-05/DK/NIDDK NIH HHS/ -- MOP-125894/Canadian Institutes of Health Research/Canada -- MOP-14409/Canadian Institutes of Health Research/Canada -- MOP-49451/Canadian Institutes of Health Research/Canada -- MOP-67011/Canadian Institutes of Health Research/Canada -- MOP-93671/Canadian Institutes of Health Research/Canada -- P30 CA014520/CA/NCI NIH HHS/ -- R01 CA104708/CA/NCI NIH HHS/ -- R01 GM051968/GM/NIGMS NIH HHS/ -- R01 GM084034/GM/NIGMS NIH HHS/ -- R01 HG005700/HG/NHGRI NIH HHS/ -- R01GM084034/GM/NIGMS NIH HHS/ -- T32 GM008061/GM/NIGMS NIH HHS/ -- Z01 DK015602-01/Intramural NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):172-7. doi: 10.1038/nature12311.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donnelly Centre, University of Toronto, Toronto M5S 3E1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23846655" target="_blank"〉PubMed〈/a〉
    Keywords: Autistic Disorder/genetics ; Base Sequence ; Binding Sites/genetics ; Conserved Sequence/genetics ; Eukaryotic Cells/metabolism ; Gene Expression Regulation/*genetics ; Humans ; Molecular Sequence Data ; Nucleotide Motifs/*genetics ; Protein Structure, Tertiary/genetics ; RNA Stability/genetics ; RNA-Binding Proteins/chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
    Electronic Resource
    Electronic Resource
    Synthesis and inhibition of human acrosin and trypsin and acute toxicity of aryl 4-guanidinobenzoates (1986)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 29 (1986), S. 514-519 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00154a015
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  • 5
    Electronic Resource
    Electronic Resource
    In situ measurements of hydrogen motion and bonding in silicon (1990)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 68 (1990), S. 3268-3284 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Hydrogenation of both n- and p-type metal/thin oxide/silicon diodes has been studied using high frequency capacitance profiling. In situ observations of donor and acceptor passivation were made while H ions were implanted through thin gate metallizations at various energies and fluxes. TRIM code simulations of the implantation process as well as studies of the energy, dose, and flux dependence of capacitance data lead us to conclude that irradiation of 400 A(ring) Al gated diodes with 800–1400 eV H ions rapidly establishes a time-independent near-surface H concentration which is proportional to both the ion flux and the implantation depth, and inversely proportional to the hydrogen diffusivity. While direct measurement of ion transits at a variety of electric fields establish that a unique mobility can be assigned to positive H ions, modeling of low and high field data in both n- and p-type samples is consistent with the notion that the positive charge state is occupied only 1/10 of the time. The time dependence of hydrogen penetration for both n- and p-type diodes indicates that hydrogen is, in addition to being trapped at unpassivated shallow donors or acceptors, becoming immobilized at other sites in silicon. The density of these secondary trapping sites correlates well with the shallow dopant population, suggesting that additional hydrogen may become trapped near already-passivated dopant atoms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.346378
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of void size and gas content on electrical breakdown in lightweight, mechanically compliant, void-filled dielectrics (2002)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 91 (2002), S. 3205-3212 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Dielectric potting materials (encapsulants) are used to prevent air breakdown in high-voltage electrical devices. We report breakdown strengths in void-filled encapsulants, stressed with unipolar voltage pulses of the order of 10 μs duration. High strengths, on the order of 100 kV mm−1, are measured under these test conditions. The materials studied include low-density open celled gel-derived foams with cell sizes of 4 μm or less, closed celled CO2-blown polystyrene and urethane foams, and epoxies containing 48 vol % of hollow glass microballoon (GMB) fillers. These last specimens varied the void gas (N2 or SO2) and also the void diameters (tens to hundreds of μm). Our measurements are thought to be directly sensitive to the rate of field-induced ionization events in the void gas; however, the breakdown strengths of the materials tested appeared to vary in direct proportion with the conventional Paschen-law gas-discharge inception threshold, the electric stress at which gas-ionization avalanches become possible. The GMB-epoxy specimens displayed this type of dependence of breakdown strength on the void-gas density and void size, but the measurements were an order of magnitude above the conventional predictions. Small-celled foams also showed increased breakdown strengths with decreased cell size, although their irregular void geometry prevented a direct comparison with the more uniformly structured microballoon-filled encapsulants. The experimental observations are consistent with a breakdown mechanism in which the discharge of a few voids can launch a full breakdown in the composite material. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1445284
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  • 7
    Electronic Resource
    Electronic Resource
    Pulsed electrical breakdown of a void-filled dielectric (2002)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 91 (2002), S. 5962-5971 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We report breakdown strengths in a void-filled dielectric material, epoxy containing 48 vol % hollow glass microballoon filler, which is stressed with unipolar voltage pulses of the order of 10 μs duration. The microballoon voids had mean diameters of approximately 40 μm and contained SO2 gas at roughly 30% atmospheric pressure. This void-filled material displays good dielectric strength (of the order of 100 kV mm−1) under these short-pulse test conditions. Results from a variety of electrode geometries are reported, including arrangements in which the electric stress is highly nonuniform. Conventional breakdown criteria based on mean or peak electric stress do not account for these data. A statistics-based predictive breakdown model is developed, in which the dielectric is divided into independent, microballoon-sized "discharge cells" and the spontaneous discharge of a single cell is presumed to launch full breakdown of the composite. We obtain two empirical parameters, the mean and standard deviation of the spontaneous discharge field, by fitting breakdown data from two electrode geometries having roughly uniform fields but with greatly differing volumes of electrically stressed material. This model accounts for many aspects of our data, including the inherent statistical scatter and the dependence on the stressed volume, and it provides informative predictions with electrode geometries giving highly nonuniform fields. Issues related to computational spatial resolution and cutoff distance are also discussed. © 2002 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1461058
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  • 8
    Electronic Resource
    Electronic Resource
    Hydroxylysine in Proteins (1955)
    s.l. : American Chemical Society
    Journal of the American Chemical Society 77 (1955), S. 2892-2893 
    Details
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ja01615a068
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  • 9
    Electronic Resource
    Electronic Resource
    Charge state control of hydrogenation in silicon (1996)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 80 (1996), S. 151-155 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We demonstrate that periodic exposure to zero bias during in situ hydrogenation of reverse-biased p-type Schottky barrier structures has dramatic effects on H penetration. H influx can be slowed or even stopped by such protocols. By contrast, similar pulsing techniques produce almost no changes of penetration in n-type barriers during hydrogenation; this latter observation is in sharp contrast to the expectations that charge conversion from H+ to H− would reverse the drift of H species. We suggest that these effects are caused by the charge conversion of relatively immobile H-related defects. In the p-type barriers this results in a weakening or reversal of the near surface electric field, effectively stopping the drift of H+ into the bulk. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.362825
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  • 10
    Electronic Resource
    Electronic Resource
    Ion Exchange Chromatography of Amino Acids. Semiautomatic Method of Operation with Cationic Exchange Resin Columns (1959)
    s.l. : American Chemical Society
    Analytical chemistry 31 (1959), S. 1504-1512 
    Details
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/ac60153a028
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