326 research outputs found

    Misunderstanding corruption and community: comparative cultural politics of corruption regulation in the Pacific

    Get PDF
    This paper will take as its empirical foundation the author’s experience of corruption and regulation in small Pacific island states. The argument is that notions of corruption and strategies for its regulation suitable for modernized societies, which lack cultural specificity and community engagement, may in fact stimulate corruption relationships in transitional cultures. The other consequence of the imposition of inappropriate definitions and regulation strategies is a profound misunderstanding of communities of dependence. In fact, corruption control can misconstrue and exacerbate economic and political dependence environments, fostering the conditions for corruption which accompany socio-economic development. Two remedies are suggested. First, corruption requires an appreciation which is ‘community-centered’, while at the same time not being neutralized by disconnected cultural relativity. Second, an enterprise theory of corruption in modernized societies and international political/commercial entities may assist in the relevant translation of global anti-corruption policies in a way which advances good governance in traditional communities. This is so when corruption is conceived as dependant on phases of modernization, and the tensions which arise when the interests of societies at different phases intersect. Corporate citizenship and compliance with anti-corrupt business practices by major corporations with a commercial interest in these transitional economies may be more beneficial than deference to uniform international codes of governance

    Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis.

    Get PDF
    The phosphoinositide 3-kinase (PI3K)-Akt network is tightly controlled by feedback mechanisms that regulate signal flow and ensure signal fidelity. A rapid overshoot in insulin-stimulated recruitment of Akt to the plasma membrane has previously been reported, which is indicative of negative feedback operating on acute timescales. Here, we show that Akt itself engages this negative feedback by phosphorylating insulin receptor substrate (IRS) 1 and 2 on a number of residues. Phosphorylation results in the depletion of plasma membrane-localised IRS1/2, reducing the pool available for interaction with the insulin receptor. Together these events limit plasma membrane-associated PI3K and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) synthesis. We identified two Akt-dependent phosphorylation sites in IRS2 at S306 (S303 in mouse) and S577 (S573 in mouse) that are key drivers of this negative feedback. These findings establish a novel mechanism by which the kinase Akt acutely controls PIP3 abundance, through post-translational modification of the IRS scaffold

    Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.

    Get PDF
    Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases

    Rapid Molecular Assays for Specific Detection and Quantitation of Loa loa Microfilaremia

    Get PDF
    Loa loa is a filarial nematode that infects over 10 million people in Africa. Most infections cause no symptoms, but individuals with large numbers of blood-stage microfilariae are at risk for fatal reactions to ivermectin, an antiparasitic agent used to treat and prevent infections with Onchocerca volvulus, a related filarial parasite that may occur alongside L. loa. To address the urgent need for a point-of-care L. loa diagnostic assay, we screened a Loa microfilaria gene expression library and identified 18 Loa-specific DNA targets. From two targets, we developed a novel, rapid quantitative PCR assay for estimating L. loa microfilaria burden. The assay is highly sensitive (detects a single microfilaria in 20 µL of blood) and correlates well with microfilaria counts obtained with conventional microscopic techniques. The assay is species-specific for L. loa compared with related filarial parasites (including O. volvulus) and can be used in its current form in resource-rich areas as a diagnostic tool for L. loa infection. Although modifications will be required to make point-of-care use feasible, our assay provides a proof of concept for a potentially valuable tool to identify individuals at risk for adverse reactions to ivermectin and to facilitate the implementation of filarial control programs
    • …
    corecore