170 research outputs found

    Open Education an (Hochschul-)Bibliotheken: Ideen und Strukturen

    Get PDF
    Workshop 7: Open Educational Resources als gemeinsames Zukunftsprojekt für Hochschulen und Bibliotheken: Potentiale und Strategie

    Geometrical principles of homomeric β-barrels and β-helices: Application to modeling amyloid protofilaments

    Get PDF
    Examples of homomeric β-helices and β-barrels have recently emerged. Here we generalise the theory for the shear number in β-barrels to encompass β-helices and homomeric structures. We introduce the concept of the “β-strip”, the set of parallel or antiparallel neighbouring strands, from which the whole helix can be generated giving it n-fold rotational symmetry. In this context the shear number is interpreted as the sum around the helix of the fixed register shift between neighbouring identical β-strips. Using this approach we have derived relationships between helical width, pitch, angle between strand direction and helical axis, mass per length, register shift, and number of strands. The validity and unifying power of the method is demonstrated with known structures including α-haemolysin, T4 phage spike, cylindrin, and the HET-s(218-289) prion. From reported dimensions measured by X-ray fibre diffraction on amyloid fibrils the relationships can be used to predict the register shift and the number of strands within amyloid protofilaments. This was used to construct models of transthyretin and Alzheimer β(40) amyloid protofilaments that comprise a single strip of in-register β-strands folded into a “β-strip helix”. Results suggest both stabilisation of an individual β-strip helix as well as growth by addition of further β-strip helices involves the same pair of sequence segments associating with β-sheet hydrogen bonding at the same register shift. This association would be aided by a repeat sequence. Hence understanding of how the register shift (as the distance between repeat sequences) relates to helical dimensions, will be useful for nanotube design

    Ability of phages to infect Acinetobacter calcoaceticus-Acinetobacter baumannii complex species through acquisition of different pectate lyase depolymerase domains

    Get PDF
    Bacteriophages are ubiquitous in nature and represent a vast repository of genetic diversity, which is driven by the endless coevolution cycle with a diversified group of bacterial hosts. Studying phage-host interactions is important to gain novel insights into their dynamic adaptation. In this study, we isolated 12 phages infecting species of the Acinetobacter baumannii-Acinetobacter calcoaceticus complex which exhibited a narrow host range and similar morphological features (podoviruses with short tails of 9-12 nm and isometric heads of 50-60 nm). Notably, the alignment of the newly sequenced phage genomes (40-41 kb of DNA length) and all Acinetobacter podoviruses deposited in Genbank has shown high synteny, regardless of the date and source of isolation that spans from America to Europe and Asia. Interestingly, the C-terminal pectate lyase domain of these phage tail fibers is often the only difference found among these viral genomes, demonstrating a very specific genomic variation during the course of their evolution. We proved that the pectate lyase domain is responsible for phage depolymerase activity and binding to specific Acinetobacter bacterial capsules. We discuss how this mechanism of phage-host co-evolution impacts the tail specificity apparatus of Acinetobacter podoviruses.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI01–0145-FEDER-006684) and the Project PTDC/BBB-BSS/6471/2014 (POCI-01–0145-FEDER-016678). This work was also supported by BioTecNorte operation (NORTE-01–0145FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. We acknowledge Dr. Lenie Dijkshoorn (Leiden Medical Center) for the provision of some strains (LUH or RUH designations). AFM was performed at i3s- Instituto de Investigação e Inovação para a Sa ude at the Biointerfaces and Nanotechnology platform. SS is an FCT Investigator (IF/01413/ 2013). HO and ARC acknowledge FCT for grants SFRH/BPD/ 111653/2015 and SFRH/BPD/94648/2013 respectively. The authors declare that they have no competing financial interests.info:eu-repo/semantics/publishedVersio

    A Multivalent Adsorption Apparatus Explains the Broad Host Range of Phage phi92: a Comprehensive Genomic and Structural Analysis

    Get PDF
    Bacteriophage phi92 is a large, lytic myovirus isolated in 1983 from pathogenic Escherichia coli strains that carry a polysialic acid capsule. Here we report the genome organization of phi92, the cryoelectron microscopy reconstruction of its virion, and the re-investigation of its host specificity. The genome consists of a linear, double-stranded 148,612-bp DNA sequence containing 248 potential open reading frames and 11 putative tRNA genes. Orthologs were found for 130 of the predicted proteins. Most of the virion proteins showed significant sequence similarities to proteins of myoviruses rv5 and PVP-SE1, indicating that phi92 is a new member of the novel genus of rv5-like phages. Reinvestigation of phi92 host specificity showed that the host range is not limited to polysialic acid-encapsulated Escherichia coli but includes most laboratory strains of Escherichia coli and many Salmonella strains. Structure analysis of the phi92 virion demonstrated the presence of four different types of tail fibers and/or tail-spikes, which enable the phage to use attachment sites on encapsulated and nonencapsulated bacteria. With this report, we provide the first detailed description of a multivalent, multispecies phage armed with a host cell adsorption apparatus resembling a nanosized Swiss army knife. The genome, structure, and, in particular, the organization of the baseplate of phi92 demonstrate how a bacteriophage can evolve into a multi-pathogen-killing agent

    Polysialic Acid/Neural Cell Adhesion Molecule Modulates the Formation of Ductular Reactions in Liver Injury

    Get PDF
    In severe liver injury, ductular reactions (DRs) containing bipotential hepatic progenitor cells (HPCs) branch from the portal tract. Neural cell adhesion molecule (NCAM) marks bile ducts and DRs, but not mature hepatocytes. NCAM mediates interactions between cells and surrounding matrix; however, its role in liver development and regeneration is undefined. Polysialic acid (polySia), a unique posttranslational modifier of NCAM, is produced by the enzymes, ST8SiaII and ST8SiaIV, and weakens NCAM interactions. The role of polySia with NCAM synthesizing enzymes ST8SiaII and ST8SiaIV were examined in HPCs in vivo using the choline‐deficient ethionine‐supplemented and 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine diet models of liver injury and regeneration, in vitro using models of proliferation, differentiation, and migration, and by use of mouse models with gene defects in the polysialyltransferases (St8sia 2+/−4+/−, and St8sia2−/−4−/−). We show that, during liver development, polySia is required for the correct formation of bile ducts because gene defects in both the polysialyltransferases (St8sia2+/−4+/− and St8sia2−/−4−/− mice) caused abnormal bile duct development. In normal liver, there is minimal polySia production and few ductular NCAM+ cells. Subsequent to injury, NCAM+ cells expand and polySia is produced by DRs/HPCs through ST8SiaIV. PolySia weakens cell‐cell and cell‐matrix interactions, facilitating HGF‐induced migration. Differentiation of HPCs to hepatocytes in vitro results in both transcriptional down‐regulation of polySia and cleavage of polySia‐NCAM. Cleavage of polySia by endosialidase (endoN) during liver regeneration reduces migration of DRs into parenchyma. Conclusion: PolySia modification of NCAM+ ductules weakens cell‐cell and cell‐matrix interactions, allowing DRs/HPCs to migrate for normal development and regeneration. Modulation of polySia levels may provide a therapeutic option in liver regeneration. (Hepatology 2014;60:1727–1740
    corecore