13 research outputs found

    Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease

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    Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium

    Psychosocial Impact of Fracking: a Review of the Literature on the Mental Health Consequences of Hydraulic Fracturing

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    The process of natural gas extraction known as hydraulic fracturing, or fracking, is a controversial energy acquisition technique often viewed with disdain by the public, due to its potential for environmental harm. However, the mental health and psychological well-being of fracking communities, including potential benefits and detriments, are often overlooked. We reviewed the literature on the association between fracking and psychological functioning, finding that although persons living in fracking communities may experience some minimal, initial benefits such as land lease income or infrastructure development, they may also experience worry, anxiety, and depression about lifestyle, health, safety, and financial security, as well as exposure to neurotoxins and changes to the physical landscape. Indeed, entire communities can experience collective trauma as a result of the “boom/bust” cycle that often occurs when industries impinge on community life. Impacted communities are often already vulnerable, including poor, rural, or indigenous persons, who may continue to experience the deleterious effects of fracking for generations. An influx of workers to fracking communities often stokes fears about outsiders and crime; yet, it must be recognized that this population of mobile workers is also vulnerable, often ostracized, and without social support. Practitioners, researchers, and policy makers alike should continue to investigate the potential psychological ramifications of fracking, so that effective and targeted intervention strategies can be developed, disseminated, and implemented to improve mental health in fracking communities

    A Link between FXYD3 (Mat-8)-mediated Na,K-ATPase Regulation and Differentiation of Caco-2 Intestinal Epithelial Cells

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    FXYD3 (Mat-8) proteins are regulators of Na,K-ATPase. In normal tissue, FXYD3 is mainly expressed in stomach and colon, but it is also overexpressed in cancer cells, suggesting a role in tumorogenesis. We show that FXYD3 silencing has no effect on cell proliferation but promotes cell apoptosis and prevents cell differentiation of human colon adenocarcinoma cells (Caco-2), which is reflected by a reduction in alkaline phosphatase and villin expression, a change in several other differentiation markers, and a decrease in transepithelial resistance. Inhibition of cell differentiation in FXYD3-deficient cells is accompanied by an increase in the apparent Na+ and K+ affinities of Na,K-ATPase, reflecting the absence of Na,K-pump regulation by FXYD3. In addition, we observe a decrease in the maximal Na,K-ATPase activity due to a decrease in its turnover number, which correlates with a change in Na,K-ATPase isozyme expression that is characteristic of cancer cells. Overall, our results suggest an important role of FXYD3 in cell differentiation of Caco-2 cells. One possibility is that FXYD3 silencing prevents proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose functional properties are incompatible with Caco-2 cell differentiation

    Arsenite Binding to Natural Organic Matter: Spectroscopic Evidence for Ligand Exchange and Ternary Complex Formation

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    The speciation of As in wetlands is often controlled by natural organic matter (NOM), which can form strong complexes with Fe(III). Here, we elucidated the molecular-scale interaction of arsenite (As(III)) with Fe(III)–NOM complexes under reducing conditions. We reacted peat (40–250 μm size fraction, 1.0 g Fe/kg) with 0–15 g Fe/kg at pH <2, removed nonreacted Fe, and subsequently equilibrated the Fe(III) complexes formed with 900 mg As/kg peat at pH 7.0, 8.4, and 8.8. The solid-phase speciation of Fe and As was studied by electron paramagnetic resonance (Fe) and X-ray absorption spectroscopy (As, Fe). Our results show that the majority of Fe in the peat was present as mononuclear Fe(III) species (RFe–C = 2.82–2.88 Å), probably accompanied by small Fe(III) clusters of low nuclearity (RFe–Fe = 3.25–3.46 Å) at high pH and elevated Fe contents. The amount of As(III) retained by the original peat was 161 mg As/kg, which increased by up to 250% at pH 8.8 and an Fe loading of 7.3 g/kg. With increasing Fe content of peat, As(III) increasingly formed bidentate mononuclear (RAs–Fe = 2.88–2.94 Å) and monodentate binuclear (RAs–Fe = 3.35–3.41 Å) complexes with Fe, thus yielding direct evidence of ternary complex formation. The ternary complex formation went along with a ligand exchange reaction between As(III) and hydroxylic/phenolic groups of the peat (RAs–C = 2.70–2.77 Å). Our findings thus provide spectroscopic evidence for two yet unconfirmed As(III)–NOM interaction mechanisms, which may play a vital role in the cycling of As in sub- and anoxic NOM-rich environments such as peatlands, peaty sediments, swamps, or rice paddies
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