103 research outputs found

    Researching COVID-19: A Research Agenda for Public Policy and Administration Scholars

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    Coronavirus (COVID-19) is one of the defining policy challenges of an era. In this article we sketch some possible ways in which the public policy and administration (PPA) scholarly community can make an enduring contribution about how to cope with this terrible crisis. We do so by offering some elements that to delineate a tentative research agenda for PPA scholars, to be pursued with epistemic humility. We outline the contours of seven analytical themes that are central to the challenges presented by COVID-19: policy design and instruments; policy learning; public service and its publics; organisational capacity; public governance; administrative traditions; and public sector reforms in multi-level governance (MLG). The list is neither exhaustive nor exclusive to COVID-19 only. The knowledge the PPA scholarly community can generate must speak not only to the daunting challenge of COVID-19 itself but also to policymakers, and indeed humankind, trying to cope with future unexpected but high impact threats (‘black swans’), by leveraging better public policies and building administrative capacities to enable more resilient, equitable and effective public services

    Defining motility in the Staphylococci

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    The ability of bacteria to move is critical for their survival in diverse environments and multiple ways have evolved to achieve this. Two forms of motility have recently been described for Staphylococcus aureus, an organism previously considered to be non-motile. One form is called spreading, which is a type of sliding motility and the second form involves comet formation, which has many observable characteristics associated with gliding motility. Darting motility has also been observed in Staphylococcus epidermidis. This review describes how motility is defined and how we distinguish between passive and active motility. We discuss the characteristics of the various forms of Staphylococci motility, the molecular mechanisms involved and the potential future research directions

    Formation and Toxicity of Soluble Polyglutamine Oligomers in Living Cells

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    Aggregation and cytotoxicity of mutant proteins containing an expanded number of polyglutamine (polyQ) repeats is a hallmark of several diseases, including Huntington's disease (HD). Within cells, mutant Huntingtin (mHtt) and other polyglutamine expansion mutant proteins exist as monomers, soluble oligomers, and insoluble inclusion bodies (IBs). Determining which of these forms constitute a toxic species has proven difficult. Recent studies support a role for IBs as a cellular coping mechanism to sequester levels of potentially toxic soluble monomeric and oligomeric species of mHtt.When fused to a fluorescent reporter (GFP) and expressed in cells, the soluble monomeric and oligomeric polyglutamine species are visually indistinguishable. Here, we describe two complementary biophysical fluorescence microscopy techniques to directly detect soluble polyglutamine oligomers (using Htt exon 1 or Htt(ex1)) and monitor their fates in live cells. Photobleaching analyses revealed a significant reduction in the mobilities of mHtt(ex1) variants consistent with their incorporation into soluble microcomplexes. Similarly, when fused to split-GFP constructs, both wildtype and mHtt(ex1) formed oligomers, as evidenced by the formation of a fluorescent reporter. Only the mHtt(ex1) split-GFP oligomers assembled into IBs. Both FRAP and split-GFP approaches confirmed the ability of mHtt(ex1) to bind and incorporate wildtype Htt into soluble oligomers. We exploited the irreversible binding of split-GFP fragments to forcibly increase levels of soluble oligomeric mHtt(ex1). A corresponding increase in the rate of IBs formation and the number formed was observed. Importantly, higher levels of soluble mHtt(ex1) oligomers significantly correlated with increased mutant cytotoxicity, independent of the presence of IBs.Our study describes powerful and sensitive tools for investigating soluble oligomeric forms of expanded polyglutamine proteins, and their impact on cell viability. Moreover, these methods should be applicable for the detection of soluble oligomers of a wide variety of aggregation prone proteins

    AMPK in Pathogens

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    During host–pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host–pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.CIHR -Canadian Institutes of Health Researc

    Police performance measurement: an annotated bibliography

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    This study provides information to assist those involved in performance measurement in police organisations. The strategies used to identify the literature are described. Thematic sections cover; general overviews; methodological issues; performance management in other industries; national, international and cross-national studies; frameworks (e.g. Compstat; the Balanced Scorecard); criticisms (particularly unintended consequences); crime-specific measures; practitioner guides; performance evaluation of individual staff; police department plans and evaluations; annotated bibliographies in related areas, and; other literature. Our discussion offers two conclusions: the measures best aligned with performance are typically more expensive, while most operational data should only provide contextual information; the philosophy of open governance should be pursued to promote transparency, accountability and communication to improve police performance

    Fiscal policy and ecological sustainability: a post-Keynesian perspective

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    Fiscal policy has a strong role to play in the transition to an ecologically sustainable economy. This paper critically discusses the way that green fiscal policy has been analysed in both conventional and post-Keynesian approaches. It then uses a recently developed post-Keynesian ecological macroeconomic model in order to provide a comparative evaluation of three different types of green fiscal policy: carbon taxes, green subsidies and green public investment. We show that (i) carbon taxes reduce global warming but increase financial risks due to their adverse effects on the profitability of firms and credit availability; (ii) green subsidies and green public investment improve ecological efficiency, but their positive environmental impact is partially offset by their macroeconomic rebound effects; and (iii) a green fiscal policy mix derives better outcomes than isolated policies. Directions for future heterodox macroeconomic research on the links between fiscal policy and ecological sustainability are suggested

    Height, weight and haemoglobin status of 6 to 59-month-old Kazakh children living in Kzyl-Orda region, Kazakhstan.

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    OBJECTIVE: To estimate the prevalence of stunting, wasting and anaemia among children aged 6-59 months in the Kzyl-Orda region of Kazakhstan, and to determine the association between childhood height and haemoglobin concentration and a range of environmental and biological factors. DESIGN: A cross-sectional study using a randomly selected sample. The mothers of children were interviewed, and finger-prick blood samples and anthropometric measurements were collected on both mothers and their children. Associations between haemoglobin (Hb) concentration, anthropometric measurements and questionnaire data were evaluated by multivariate analysis. SETTING: Health centres in Kazalinsk, Djalagash and Zhanakorgan districts of Kzyl-Orda region, Kazakhstan. SUBJECTS: Two-thousand and twenty-four children aged between 6 and 59 months born to 1501 mothers who were randomly selected from health centre records. RESULTS: The overall prevalence of stunting (<-2.0 Z-scores height for age), wasting (<-2.0 Z-scores weight for height) and anaemia (Hb<11.0 g/dl) in the study children was found to be 15.8, 0.8 and 50.1%, respectively. However, analysis demonstrated considerable variation by age, with the second year of life showing the highest prevalence of both stunting and anaemia. Both childhood height and haemoglobin concentration were found to be significantly associated with a range of environmental and maternal variables. CONCLUSIONS: This study demonstrates that the prevalence of both stunting and anaemia among Kazakh children in the Kzyl-Orda region is considerable, and similar to that of other Central Asian children. These findings highlight Central Asia as a region with levels of childhood nutritional status that are of concern. SPONSORSHIP: Funding was provided by the United States Agency for International Development, Office of Nutrition, the United Kingdom Department for International Development, and the Polden-Puckham Trust
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