56 research outputs found

    N-Glycans and Glycosylphosphatidylinositol-Anchor Act on Polarized Sorting of Mouse PrPC in Madin-Darby Canine Kidney Cells

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    The cellular prion protein (PrPC) plays a fundamental role in prion disease. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein with two variably occupied N-glycosylation sites. In general, GPI-anchor and N-glycosylation direct proteins to apical membranes in polarized cells whereas the majority of mouse PrPC is found in basolateral membranes in polarized Madin-Darby canine kidney (MDCK) cells. In this study we have mutated the first, the second, and both N-glycosylation sites of PrPC and also replaced the GPI-anchor of PrPC by the Thy-1 GPI-anchor in order to investigate the role of these signals in sorting of PrPC in MDCK cells. Cell surface biotinylation experiments and confocal microscopy showed that lack of one N-linked oligosaccharide leads to loss of polarized sorting of PrPC. Exchange of the PrPC GPI-anchor for the one of Thy-1 redirects PrPC to the apical membrane. In conclusion, both N-glycosylation and GPI-anchor act on polarized sorting of PrPC, with the GPI-anchor being dominant over N-glycans

    A media framing analysis of urban flooding in Nigeria: current narratives and implications for policy

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    © 2017, The Author(s). A critical element of current flood management is the importance of engaging key policy actors when policy decisions are to be made. However, there is still only limited understanding of how narratives of flood management actors may influence flood management policies, even though there is a suggestion that actors can strategically use their narratives to influence policy directions. In a developing country like Nigeria, there are still questions around lessons that can be learnt from understanding the narratives of policy actors, to unravel the complex nature of strategies and policy directions in managing urban floods. To help fill these gaps, this paper uses quantitative content analysis to explore the frame of five policy actor groups (government, local communities, business, multilateral organisations and non-governmental organisations (NGOs)) as expressed in local and national newspapers between 2012 and 2016 to understand their narratives of causes and strategies to solve the problem of urban flooding in Nigeria. The narratives of government, local communities and businesses align with the premise that flooding can and should be prevented whilst that of multilateral and business actors champion adaptation strategies on the basis that flooding is inevitable and hence more energy should be directed at ‘living with water’—emergency response, damage reduction and the aftermath. The study also identified areas of potential consensus and conflict between direct actors such as government and local communities on the one hand and funders on the other. Better discussion among actors aiding understanding of contemporary thinking and local realities will aid policy-making and policy implementation in the Nigerian context. An important step will be in the collaborative design of an urgently needed ‘Nigerian policy on flooding’ which currently does not exist

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

    Natural environments, ancestral diets, and microbial ecology: is there a modern “paleo-deficit disorder”? Part II

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    Antiferromagnetism in UO2 thin epitaxial films

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    Thin films (250-4500 Å) of epitaxial UO2 were produced by reactive sputtering on two different substrate materials: LaAlO3 and CaF2. Using the large enhancement present with resonant x-ray scattering using photons at the uranium M4 absorption edge, antiferromagnetic (AF) order was found in all films. The ordering temperature TN is the same as the bulk, but the films show second-order (continuous) transitions in contrast to the first-order bulk transition. For LaAlO3-based films, an additional strong diffuse magnetic disorder is observed, which is reminiscent of the second-length scale, associated with structural disorder and/or strain. By using a formulation accounting for the strong absorption and coherent nature of the photons, the energy widths at the U M4 resonances can be related to the thickness of the AF region. The LaAlO3-based films do not order magnetically over more than ∼600 Å, whereas the CaF2-based film orders throughout. Further, for thicker films (>1000 Å) the fitting procedure shows that the AF order is located at the top of the LaAlO3-based film. This points to the formation in thicker films of a nonmagnetic layer of UO2 adjacent to the substrate, which may have tetragonal symmetry. © 2013 American Physical Society

    Antiferromagnetism in UO2 thin epitaxial films

    No full text
    Thin films (250-4500 Å) of epitaxial UO2 were produced by reactive sputtering on two different substrate materials: LaAlO3 and CaF2. Using the large enhancement present with resonant x-ray scattering using photons at the uranium M4 absorption edge, antiferromagnetic (AF) order was found in all films. The ordering temperature TN is the same as the bulk, but the films show second-order (continuous) transitions in contrast to the first-order bulk transition. For LaAlO3-based films, an additional strong diffuse magnetic disorder is observed, which is reminiscent of the second-length scale, associated with structural disorder and/or strain. By using a formulation accounting for the strong absorption and coherent nature of the photons, the energy widths at the U M4 resonances can be related to the thickness of the AF region. The LaAlO3-based films do not order magnetically over more than ∼600 Å, whereas the CaF2-based film orders throughout. Further, for thicker films (>1000 Å) the fitting procedure shows that the AF order is located at the top of the LaAlO3-based film. This points to the formation in thicker films of a nonmagnetic layer of UO2 adjacent to the substrate, which may have tetragonal symmetry. © 2013 American Physical Society
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