1,881 research outputs found

    ERp29 triggers a conformational change in polyomavirus to stimulate membrane binding

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    Funding Information: We thank Tom Rapoport and Kristen Verhey for critically reading the manuscript. B.T. is a Biological Scholar at the University of Michigan Medical School. E.K.R. is supported by a training grant from the National Science Foundation. S.M. was supported by the Swedish Medical Research Council and the Swedish Society of Medicine. M.B. received a scholarship from the Royal Swedish Academy. The work was supported in part by a grant to T.B. from the National Cancer Institute (CA 082395). Copyright: Copyright 2008 Elsevier B.V., All rights reserved.Membrane penetration of nonenveloped viruses is a poorly understood process. We have investigated early stages of this process by studying the conformational change experienced by polyomavirus (Py) in the lumen of the endoplasmic reticulum (ER), a step that precedes its transport into the cytosol. We show that a PDI-like protein, ERp29, exposes the C-terminal arm of Py's VP1 protein, leading to formation of a hydrophobic particle that binds to a lipid bilayer; this reaction likely mimics initiation of Py penetration across the ER membrane. Expression of a dominant-negative ERp29 decreases Py infection, indicating ERp29 facilitates viral infection. Interestingly, cholera toxin, another toxic agent that crosses the ER membrane into the cytosol, is unfolded by PDI in the ER. Our data thus identify an ER factor that mediates membrane penetration of a nonenveloped virus and suggest that PDI family members are generally involved in ER remodeling reactions.publishersversionPeer reviewe

    Electronic structure and chemical bonding in Ti2AlC investigated by soft x-ray emission spectroscopy

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    The electronic structure of the nanolaminated transition metal carbide Ti2AlC has been investigated by bulk-sensitive soft x-ray emission spectroscopy. The measured Ti L, C K and Al L emission spectra are compared with calculated spectra using ab initio density-functional theory including dipole matrix elements. The detailed investigation of the electronic structure and chemical bonding provides increased understanding of the physical properties of this type of nanolaminates. Three different types of bond regions are identified; the relatively weak Ti 3d - Al 3p hybridization 1 eV below the Fermi level, and the Ti 3d - C 2p and Ti 3d - C 2s hybridizations which are stronger and deeper in energy are observed around 2.5 eV and 10 eV below the Fermi level, respectively. A strongly modified spectral shape of the 3s final states in comparison to pure Al is detected for the buried Al monolayers indirectly reflecting the Ti 3d - Al 3p hybridization. The differences between the electronic and crystal structures of Ti2AlC, Ti3AlC2 and TiC are discussed in relation to the number of Al layers per Ti layer in the two former systems and the corresponding change of the unusual materials properties.Comment: 14 pages, 7 figures; PACS:78.70.En, 71.15.Mb, 71.20.-

    Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after SpinalCord Injury

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    Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs, and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI

    Electronic structure and chemical bonding in Ti4SiC3 investigated by soft x-ray emission spectroscopy and first principle theory

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    The electronic structure in the new transition metal carbide Ti4SiC3 has been investigated by bulk-sensitive soft x-ray emission spectroscopy and compared to the well-studied Ti3SiC2 and TiC systems. The measured high-resolution Ti L, C K and Si L x-ray emission spectra are discussed with ab initio calculations based on density-functional theory including core-to-valence dipole matrix elements. The detailed investigations of the Ti-C and Ti-Si chemical bonds provide increased understanding of the physical properties of these nanolaminates. A strongly modified spectral shape is detected for the buried Si monolayers due to Si 3p hybridization with the Ti 3d orbitals. As a result of relaxation of the crystal structure and the charge-transfer from Ti (and Si) to C, the strength of the Ti-C covalent bond is increased. The differences between the electronic and crystal structures of Ti4SiC3 and Ti3SiC2 are discussed in relation to the number of Si layers per Ti layer in the two systems and the corresponding change of materials properties.Comment: 12 pages, 7 figures, 1 tabl

    Backscattered Electron Imaging and Windowless Energy Dispersive X-Ray Microanalysis: A New Technique for Gallstone Analysis

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    Scanning electron microscopy with or without conventional energy dispersive x-ray microanalysis is currently used to identify gallstone microstructure and inorganic composition. Organic calcium salts are among many biliary constituents thought to have a role in gallstone nidation and growth. However, current analytical techniques which identify these salts are destructive and compromise gallstone microstructural data. We have developed a new technique for gallstone analysis which provides simultaneous structural and compositional identification of calcium salts within gallstones. Backscattered electron imaging is used to localize calcium within cholesterol at minimum concentrations of 0.01%. Windowless energy dispersive x-ray microanalysis produces elemental spectra of gallstone calcium salts which are qualitatively and quantitatively different. These combined techniques provide simultaneous structural and compositional information obtained from intact gallstone cross-sections and have been used to identify calcium salts in gallstones obtained at cholecystectomy from 106 patients

    Bonding mechanism in the nitrides Ti2AlN and TiN: an experimental and theoretical investigation

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    The electronic structure of nanolaminate Ti2AlN and TiN thin films has been investigated by bulk-sensitive soft x-ray emission spectroscopy. The measured Ti L, N K, Al L1 and Al L2,3 emission spectra are compared with calculated spectra using ab initio density-functional theory including dipole transition matrix elements. Three different types of bond regions are identified; a relatively weak Ti 3d - Al 3p bonding between -1 and -2 eV below the Fermi level, and Ti 3d - N 2p and Ti 3d - N 2s bonding which are deeper in energy observed at -4.8 eV and -15 eV below the Fermi level, respectively. A strongly modified spectral shape of 3s states of Al L2,3 emission from Ti2AlN in comparison to pure Al metal is found, which reflects the Ti 3d - Al 3p hybridization observed in the Al L1 emission. The differences between the electronic and crystal structures of Ti2AlN and TiN are discussed in relation to the intercalated Al layers of the former compound and the change of the materials properties in comparison to the isostructural carbides.Comment: 18 pages, 7 figures; http://link.aps.org/doi/10.1103/PhysRevB.76.19512

    The Dunaliella salina organelle genomes: large sequences, inflated with intronic and intergenic DNA

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    <p>Abstract</p> <p>Background</p> <p><it>Dunaliella salina </it>Teodoresco, a unicellular, halophilic green alga belonging to the Chlorophyceae, is among the most industrially important microalgae. This is because <it>D. salina </it>can produce massive amounts of β-carotene, which can be collected for commercial purposes, and because of its potential as a feedstock for biofuels production. Although the biochemistry and physiology of <it>D. salina </it>have been studied in great detail, virtually nothing is known about the genomes it carries, especially those within its mitochondrion and plastid. This study presents the complete mitochondrial and plastid genome sequences of <it>D. salina </it>and compares them with those of the model green algae <it>Chlamydomonas reinhardtii </it>and <it>Volvox carteri</it>.</p> <p>Results</p> <p>The <it>D. salina </it>organelle genomes are large, circular-mapping molecules with ~60% noncoding DNA, placing them among the most inflated organelle DNAs sampled from the Chlorophyta. In fact, the <it>D. salina </it>plastid genome, at 269 kb, is the largest complete plastid DNA (ptDNA) sequence currently deposited in GenBank, and both the mitochondrial and plastid genomes have unprecedentedly high intron densities for organelle DNA: ~1.5 and ~0.4 introns per gene, respectively. Moreover, what appear to be the relics of genes, introns, and intronic open reading frames are found scattered throughout the intergenic ptDNA regions -- a trait without parallel in other characterized organelle genomes and one that gives insight into the mechanisms and modes of expansion of the <it>D. salina </it>ptDNA.</p> <p>Conclusions</p> <p>These findings confirm the notion that chlamydomonadalean algae have some of the most extreme organelle genomes of all eukaryotes. They also suggest that the events giving rise to the expanded ptDNA architecture of <it>D. salina </it>and other Chlamydomonadales may have occurred early in the evolution of this lineage. Although interesting from a genome evolution standpoint, the <it>D. salina </it>organelle DNA sequences will aid in the development of a viable plastid transformation system for this model alga, and they will complement the forthcoming <it>D. salina </it>nuclear genome sequence, placing <it>D. salina </it>in a group of a select few photosynthetic eukaryotes for which complete genome sequences from all three genetic compartments are available.</p
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