47 research outputs found

    Entrapment of Viral Capsids in Nuclear PML Cages Is an Intrinsic Antiviral Host Defense against Varicella-Zoster Virus

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    The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins

    Genomic analyses inform on migration events during the peopling of Eurasia.

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    High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.Support was provided by: Estonian Research Infrastructure Roadmap grant no 3.2.0304.11-0312; Australian Research Council Discovery grants (DP110102635 and DP140101405) (D.M.L., M.W. and E.W.); Danish National Research Foundation; the Lundbeck Foundation and KU2016 (E.W.); ERC Starting Investigator grant (FP7 - 261213) (T.K.); Estonian Research Council grant PUT766 (G.C. and M.K.); EU European Regional Development Fund through the Centre of Excellence in Genomics to Estonian Biocentre (R.V.; M.Me. and A.Me.), and Centre of Excellence for Genomics and Translational Medicine Project No. 2014-2020.4.01.15-0012 to EGC of UT (A.Me.) and EBC (M.Me.); Estonian Institutional Research grant IUT24-1 (L.S., M.J., A.K., B.Y., K.T., C.B.M., Le.S., H.Sa., S.L., D.M.B., E.M., R.V., G.H., M.K., G.C., T.K. and M.Me.) and IUT20-60 (A.Me.); French Ministry of Foreign and European Affairs and French ANR grant number ANR-14-CE31-0013-01 (F.-X.R.); Gates Cambridge Trust Funding (E.J.); ICG SB RAS (No. VI.58.1.1) (D.V.L.); Leverhulme Programme grant no. RP2011-R-045 (A.B.M., P.G. and M.G.T.); Ministry of Education and Science of Russia; Project 6.656.2014/K (S.A.F.); NEFREX grant funded by the European Union (People Marie Curie Actions; International Research Staff Exchange Scheme; call FP7-PEOPLE-2012-IRSES-number 318979) (M.Me., G.H. and M.K.); NIH grants 5DP1ES022577 05, 1R01DK104339-01, and 1R01GM113657-01 (S.Tis.); Russian Foundation for Basic Research (grant N 14-06-00180a) (M.G.); Russian Foundation for Basic Research; grant 16-04-00890 (O.B. and E.B); Russian Science Foundation grant 14-14-00827 (O.B.); The Russian Foundation for Basic Research (14-04-00725-a), The Russian Humanitarian Scientific Foundation (13-11-02014) and the Program of the Basic Research of the RAS Presidium “Biological diversity” (E.K.K.); Wellcome Trust and Royal Society grant WT104125AIA & the Bristol Advanced Computing Research Centre (http://www.bris.ac.uk/acrc/) (D.J.L.); Wellcome Trust grant 098051 (Q.A.; C.T.-S. and Y.X.); Wellcome Trust Senior Research Fellowship grant 100719/Z/12/Z (M.G.T.); Young Explorers Grant from the National Geographic Society (8900-11) (C.A.E.); ERC Consolidator Grant 647787 ‘LocalAdaptatio’ (A.Ma.); Program of the RAS Presidium “Basic research for the development of the Russian Arctic” (B.M.); Russian Foundation for Basic Research grant 16-06-00303 (E.B.); a Rutherford Fellowship (RDF-10-MAU-001) from the Royal Society of New Zealand (M.P.C.)

    Reactivity of CaO derived from nano-sized CaCO<inf>3</inf> particles through multiple CO<inf>2</inf> capture-and-release cycles

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    The carbonation characteristics of pure CaO derived from nano-sized CaCO3 were investigated as part of a multi-cycle performance study which showed potential for exploiting the properties of nano-sized CaO sorbents in a continuous CO2 capture-and-release process. To help understand the approach to the decay asymptote, which is established through multiple capture-and-release cycles, a qualitative model was proposed. The rate of approach and residual conversion defined by the decay asymptote represents the establishment of an equilibrium between the pore volume and surface area loss during thermal sintering; and the pore volume and surface area regeneration as a consequence of a solid-state diffusion mechanism, and the subsequent release of CO2 in the next calcination cycle. This qualitative explanation is valid for all CaO derived CO2 sorbents. © 2008 Elsevier Ltd. All rights reserved

    Mesoporous supported cobalt catalysts for enhanced hydrogen production during cellulose decomposition

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    Two groups of cobalt (Co) catalysts, supported on SBA-15 and MCM-41, respectively, were prepared by incipient wetness impregnation and tested for their influence on the thermal decomposition of acetyl cellulose. γ-Al2O3 supported Co catalysts were investigated as a comparison. A thermogravimetric analyser coupled with a mass spectrometer (TG-MS) was used to examine the influence of catalyst loading, support material and the presence of additional water vapour on H2 production and selectivity. Normalization of the raw MS data enabled semi-quantitative analysis of the product gas distribution, which facilitated reliable comparison between different experimental conditions. Catalysts were characterized by physisorption, chemisorption, TGA, XRD, SEM and TEM. SBA-15 and MCM-41 supported catalysts significantly elevated the yield and selectivity of H2, under dry Ar and with the injection of additional water vapour, when compared with the γ-Al2O3 support. 15 wt.%Co/SBA-15 and 10 wt.%Co/MCM-41 were identified as the most active catalysts from the two groups with indicative yields of 202 and 303 ml H2/g cellulose, respectively. The 10 wt.%Co/MCM-41 catalyst gave with the highest H2 selectivity reaching 21.7% of the dry product gas. © 2010 Elsevier B.V. All rights reserved

    The influence of supported Ni catalysts on the product gas distribution and H<inf>2</inf> yield during cellulose pyrolysis

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    Two groups of Ni catalysts, supported on γ-Al2O3 and MCM-41, respectively, were prepared by incipient wetness impregnation and tested for their influence on the pyrolytic decomposition of cellulose. A thermogravimetric analyser coupled with a mass spectrometer (TG-MS) was used to examine the influence of catalyst loading, support material, and the presence of additional water vapour on H2 selectivity. Normalization of the raw MS data enabled semi-quantitative analysis of the product gas distribution, which facilitated reliable comparison between different experimental conditions. Catalysts were characterized by BET, XRD, SEM/EDX and TEM. MCM-41 supported Ni significantly elevated the yield of H2 and total gaseous product, both under Ar and with the injection of additional water vapour when compared with the γ-Al2O3 support. 15 wt.%Ni/γ-Al2O3 and 5 wt.%Ni/MCM-41 were identified as the most active catalysts from the two groups with regards to H2 selectivity and yield. © 2009 Elsevier B.V. All rights reserved

    Life cycle greenhouse gas assessment of a coal-fired power station with calcium looping CO<inf>2</inf> capture and offshore geological storage

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    Carbon Capture and Storage (CCS) is an essential technology for reducing global CO2 emissions in the context of continued fossil fuel use in the power sector. To evaluate the emission reduction potential of any low-carbon generation technology it is necessary to consider emissions over the entire lifetime of the plant. This work examines the lifecycle greenhouse gas emissions of a 500 MWe pulverised coal-fired power plant with post-combustion Calcium Looping (CaL) and off-shore geological storage. CaL uses solid CO 2-sorbent derived from abundant and non-toxic limestone (CaCO 3) and is currently being piloted at the 1-2 MWth scale in Europe (Spain and Germany). This technology promises to be very competitive with the more mature chemical absorption processes, with the potential to reduce the efficiency and cost penalties of CO2 capture. We demonstrate that the emission intensity of a coal-fired power plant with CaL is at least comparable with one using MEA-solvent technology (i.e., ∼ 229 gCO 2e/kWh vs. 225 gCO2e/kWh). However, there is significant potential for additional emissions reduction when considering the recarbonation of exhausted sorbent in landfill. Furthermore, a coal-fired power plant with CaL could be carbon-neutral - or even achieve a net removal of CO2 from the atmosphere. That is, if the exhausted sorbent is used in the cement industry substituting the input of fresh-limestone; or if the exhausted sorbent is disposed in the ocean forming bicarbonate. © 2012 The Royal Society of Chemistry

    Synthetic CaO-based sorbent for CO<inf>2</inf> capture from large-point sources

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    The main impetus for future technology development for capturing and purifying CO2 from industrial flue gases is the potential for minimizing the cost of capture and reducing the efficiency penalty that is imposed on the process. Carbonate looping is a very promising future technology, which uses CaO-based solid sorbents, with great potential to reduce the cost of capture and lessen the energy penalty compared to closer to market technologies, e.g., solvent scrubbing. Unfortunately, the CO2-capture capacity of a CaO-sorbent derived from natural limestone decays through long-term capture-and-release cycling; thus, the development of strategies and/or novel sorbents to achieve a high CO2-capture capacity is an important challenge for realizing the cost efficiency of carbonate looping technology. To this end, we report on the development and characterization of a novel synthetic CaO-based sorbent produced via a precipitation method and present experimental results demonstrating improved long-term CO 2-capture capacity based on reactivity testing using a thermogravimetric analyzer (TGA) and a bench-scale bubbling fluidized-bed (BFB) reactor. We achieve a capture capacity of about 2.5 times the amount of CO 2 after 15 cycles with the synthetic sorbent compared to a natural limestone (Havelock) in the BFB. © 2010 American Chemical Society

    Synthesis and characterization of CaO nanopods for high temperature CO <inf>2</inf> Capture

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    A hollow structured CaO sorbent with high CO2 absorption capacity and good cyclic performance at high temperatures was derived from the corresponding CaCO3 precursor, which was prepared by bubbling gaseous CO2 through a Ca(OH) 2 slurry in the presence of the triblock copolymer surfactant, P123 (PEO20PPO70PEO 20).Field-emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) images showed the novel sorbent to be comprised of nanosized platelets forming hollow particles resembling a pod of approximately 200 nm in diameter and up to 600 nm in length. Thermogravimetric analysis showed that the tailored sorbent had the highest CO2 absorption capacity when compared with calcines derived fromprecipitated CaCO3 without P123 and a commercially available CaCO3, retaining >50% CO2 absorption capacity after 50 CO2 capture-and-release cycles for carbonation temperatures from 600 to 700 °C. © 2009 American Chemical Society
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