185 research outputs found

    The CsrA-FliW network controls polar localization of the dual-function flagellin mRNA in Campylobacter jejuni

    No full text
    The widespread CsrA/RsmA protein regulators repress translation by binding GGA motifs in bacterial mRNAs. CsrA activity is primarily controlled through sequestration by multiple small regulatory RNAs. Here we investigate CsrA activity control in the absence of antagonizing small RNAs by examining the CsrA regulon in the human pathogen Campylobacter jejuni. We use genome-wide co-immunoprecipitation combined with RNA sequencing to show that CsrA primarily binds flagellar mRNAs and identify the major flagellin mRNA (flaA) as the main CsrA target. The flaA mRNA is translationally repressed by CsrA, but it can also titrate CsrA activity. Together with the main C. jejuni CsrA antagonist, the FliW protein, flaA mRNA controls CsrA-mediated post-transcriptional regulation of other flagellar genes. RNA-FISH reveals that flaA mRNA is expressed and localized at the poles of elongating cells. Polar flaA mRNA localization is translation dependent and is post-transcriptionally regulated by the CsrA-FliW network. Overall, our results suggest a role for CsrA-FliW in spatiotemporal control of flagella assembly and localization of a dual-function mRNA

    Integrated Participatory and Collaborative Risk Mapping for Enhancing Disaster Resilience

    Get PDF
    Critical knowledge gaps seriously hinder efforts for building disaster resilience at all levels, especially in disaster-prone least developed countries. Information deficiency is most serious at local levels, especially in terms of spatial information on risk, resources, and capacities of communities. To tackle this challenge, we develop a general methodological approach that integrates community-based participatory mapping processes, one that has been widely used by governments and non-government organizations in the fields of natural resources management, disaster risk reduction and rural development, with emerging collaborative digital mapping techniques. We demonstrate the value and potential of this integrated participatory and collaborative mapping approach by conducting a pilot study in the flood-prone lower Karnali river basin in Western Nepal. The process engaged a wide range of stakeholders and non-stakeholder citizens to co-produce locally relevant geographic information on resources, capacities, and flood risks of selected communities. The new digital community maps are richer in content, more accurate, and easier to update and share than those produced by conventional Vulnerability and Capacity Assessments (VCAs), a variant of Participatory Rural Appraisal (PRA), that is widely used by various government and non-government organizations. We discuss how this integrated mapping approach may provide an effective link between coordinating and implementing local disaster risk reduction and resilience building interventions to designing and informing regional development plans, as well as its limitations in terms of technological barrier, map ownership, and empowerment potential

    Metabolic and chromosomal changes in a <i>Bacillus subtilis whiA</i> mutant

    Get PDF
    The conserved protein WhiA is present in most Gram-positive bacteria and plays a role in cell division. WhiA contains a DNA-binding motif and is a transcription regulator of the key cell division gene ftsZ in actinomycetes. In Bacillus subtilis, the absence of WhiA influences both cell division and chromosome segregation; however, the protein does not regulate any gene involved in these processes. In this study, we addressed three alternative mechanisms by which WhiA might exert its activity in B. subtilis and examined whether WhiA influences either (i) central carbon metabolism, (ii) fatty acid composition of the cell membrane, or (iii) chromosome organization. Mutations in glycolytic enzymes have been shown to influence both cell division and DNA replication. To measure the effect of WhiA on carbon metabolism, we tested different carbon sources and measured exometabolome fluxes. This revealed that the absence of WhiA does not affect glycolysis but does influence the pool of branched-chain fatty acid precursors. Due to the effect of WhiA on chromosome segregation, we examine chromosome organization in a ∆whiA mutant using chromosome conformation capture (Hi-C) analysis. This revealed a local reduction in short-range chromosome interactions. Together, these findings provide new avenues for future research into how this protein works in the non-actinomycete firmicutes

    Communication, leadership and coordination failure

    Get PDF
    We investigate the limits of communication and leadership in avoiding coordination failure in minimum effort games. Our environment is challenging, with low benefits of coordination relative to the effort cost. We consider two leader types: cheap-talk leader-communicators who suggest an effort level, and first-mover leaders who lead by example. Both types of leadership have some ability to increase effort in groups with no history, but are insufficient in groups with a history of low effort. Using the strategy method for followers’ responses, we attribute the persistence of coordination failure to the presence of followers who do not follow the leader

    What is the value and impact of quality and safety teams? A scoping review

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to conduct a scoping review of the literature about the establishment and impact of quality and safety team initiatives in acute care.</p> <p>Methods</p> <p>Studies were identified through electronic searches of Medline, Embase, CINAHL, PsycINFO, ABI Inform, Cochrane databases. Grey literature and bibliographies were also searched. Qualitative or quantitative studies that occurred in acute care, describing how quality and safety teams were established or implemented, the impact of teams, or the barriers and/or facilitators of teams were included. Two reviewers independently extracted data on study design, sample, interventions, and outcomes. Quality assessment of full text articles was done independently by two reviewers. Studies were categorized according to dimensions of quality.</p> <p>Results</p> <p>Of 6,674 articles identified, 99 were included in the study. The heterogeneity of studies and results reported precluded quantitative data analyses. Findings revealed limited information about attributes of successful and unsuccessful team initiatives, barriers and facilitators to team initiatives, unique or combined contribution of selected interventions, or how to effectively establish these teams.</p> <p>Conclusions</p> <p>Not unlike systematic reviews of quality improvement collaboratives, this broad review revealed that while teams reported a number of positive results, there are many methodological issues. This study is unique in utilizing traditional quality assessment and more novel methods of quality assessment and reporting of results (SQUIRE) to appraise studies. Rigorous design, evaluation, and reporting of quality and safety team initiatives are required.</p

    Guide-free Cas9 from pathogenic Campylobacter jejuni bacteria causes severe damage to DNA

    Get PDF
    CRISPR-Cas9 systems are enriched in human pathogenic bacteria and have been linked to cytotoxicity by an unknown mechanism. Here, we show that upon infection of human cells, Campylobacter jejuni secretes its Cas9 (CjeCas9) nuclease into their cytoplasm. Next, a native nuclear localization signal enables CjeCas9 nuclear entry, where it catalyzes metal-dependent nonspecific DNA cleavage leading to cell death. Compared to CjeCas9, native Cas9 of Streptococcus pyogenes (SpyCas9) is more suitable for guide-dependent editing. However, in human cells, native SpyCas9 may still cause some DNA damage, most likely because of its ssDNA cleavage activity. This side effect can be completely prevented by saturation of SpyCas9 with an appropriate guide RNA, which is only partially effective for CjeCas9. We conclude that CjeCas9 plays an active role in attacking human cells rather than in viral defense. Moreover, these unique catalytic features may therefore make CjeCas9 less suitable for genome editing applications
    corecore