1,721,018 research outputs found

    Lysis cassette-mediated exoprotein release in Yersinia entomophaga is controlled by a PhoB-like regulator

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    Secretion of exoproteins is a key component of bacterial virulence, and is tightly regulated in response to environmental stimuli and host-dependent signals. The entomopathogenic bacterium Yersinia entomophaga MH96 produces a wide range of exoproteins including its main virulence factor, the 2.46 MDa insecticidal Yen-Tc toxin complex. Previously, a high-throughput transposon-based screening assay identified the region of exoprotein release (YeRER) as essential to exoprotein release in MH96. This study defines the role of the YeRER associated ambiguous holin/endolysin-based lysis cluster (ALC) and the novel RoeA regulator in the regulation and release of exoproteins in MH96. A mutation in the ambiguous lysis cassette (ALC) region abolished exoprotein release and caused cell elongation, a phenotype able to be restored through trans-complementation with an intact ALC region. Endogenous ALC did not impact cell growth of the wild type, while artificial expression of an optimized ALC caused cell lysis. Using HolA-sfGFP and Rz1-sfGFP reporters, Rz1 expression was observed in all cells while HolA expression was limited to a small proportion of cells, which increased over time. Transcriptomic assessments found expression of the genes encoding the prominent exoproteins, including the Yen-Tc, was reduced in the roeA mutant and identified a 220 ncRNA of the YeRER intergenic region that, when trans complemented in the wildtype, abolished exoprotein release. A model for Y. entomophaga mediated exoprotein regulation and release is proposed. IMPORTANCE While theoretical models exist, there is not yet any empirical data that links ALC phage-like lysis cassettes with the release of large macro-molecular toxin complexes, such as Yen-Tc in Gram-negative bacteria. In this study, we demonstrate that the novel Y. entomophaga RoeA activates the production of exoproteins (including Yen-Tc) and the ALC at the transcriptional level. The translation of the ALC holin is confined to a subpopulation of cells that then lyse over time, indicative of a complex hierarchical regulatory network. The presence of an orthologous RoeA and a HolA like holin 59 of an eCIS Afp element in Pseudomonas chlororaphis, combined with the presented data, suggests a shared mechanism is required for the release of some large macromolecular protein assemblies, such as the Yen-Tc, and further supports classification of phage-like lysis clusters as type 10 secretion systems

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Analysis of Phase-variable Genes in Human-adapted Bacterial Pathogens

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    This thesis contributes significantly to the understanding of phase-variable gene expression in Haemophilus influenzae and phasevarions in Streptococcus pneumoniae, and to the broader fields of bacterial genetics and epigenetics. This thesis has: (i) demonstrated that particular forms of lipooligosaccharide (LOS) are selected for during NTHi invasive infection; (ii) described the autotransporter Lav in NTHi, demonstrating that this protein is phase-variable, is an important virulence factor, and is a potential NTHi vaccine candidate; (iii) informed vaccine development by characterising the prevalence of Hgps across Haemophilus influenzae, while identifying expression in an invasive NTHi isolate collection; (iv) effectively doubled publicly available genomes for Haemophilus influenzae biogroup aegyptius isolates; and (v) carried out a detailed analysis of the pathobiology of the SpnIII system of S. pneumoniae. As the body of work that constitutes each Chapter of this thesis is in manuscript format, abstracts can be found in these Chapters.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)Institute for GlycomicsGriffith HealthFull Tex

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Defining the 'Glycointeractome' of Acinetobacter baumannii

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    Acinetobacter baumannii is a major multi-drug resistant nosocomial pathogen and the cause of a significant number of hospital-acquired infections worldwide for which new treatment options are urgently needed. Due to the multi-drug resistance and prevalence of A. baumannii it is considered a critical top priority pathogen for research and development of new therapies and treatments by the World Health Organisation (WHO) and Centres for Disease Control and Prevention (CDC). A. baumannii encodes several major outer membrane proteins, called adhesins, that have all previously been determined to be involved in host adherence, and more broadly in pathobiology. However, the specific host receptors that these outer-membrane proteins interact with remains undefined. Our lab has demonstrated, for the first time, that a major A. baumannii surface adhesin, Ata, interacts with host glycans with high affinity. Ata bound to terminal and core galactose and Nacetylglucosamine structures with high affinity. The interaction of Ata with the host extracellular matrix (ECM) protein fibronectin, which is heavily glycosylated, was absolutely dependent of the presence of these glycan structures, as no interaction between Ata and deglycosylated fibronectin occurred. This Masters research project, demonstrates that the major outer-membrane protein from A. baumannii, OmpA, interacts with host glycans. Using a parallel approach of heterologousover-expression of OmpA at the E.coli cell surface, characterisation of purified protein, and study of knock-out mutants in A. baumannii, demonstrated that this major A. baumannii virulence factor interacts directly with host glycan moieties such as; Lewis antigens, Blood group H antigen, fucosyllatose structures, O-glycans like Tn and sTn. This knowledge will enable further investigation of precisely how A. baumannii interacts with the human host and pave the way for new ways to treat infections caused by a major human pathogen for which traditional antibiotics are rapidly becoming ineffective.Thesis (Masters)Master of Medical Research (MMedRes)School of Pharmacy & Med SciGriffith HealthFull Tex

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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