7,098 research outputs found

    Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury

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    We hypothesized that the store-operated calcium entry (SOCE) channel, Orai1, participates in the activation of Th17 cells and influences renal injury. In rats, following renal ischemia/reperfusion (I/R), there was a rapid and sustained influx of Orai1+ CD4 T cells and IL-17 expression was restricted to Orai1+ cells. When kidney CD4+ cells of post-acute kidney injury (post-AKI) rats were stimulated with angiotensin II and elevated Na+ (10-7 M/170 mM) in vitro, there was an enhanced response in intracellular Ca2+ and IL-17 expression, which was blocked by SOCE inhibitors 2APB, YM58483/BTP2, or AnCoA4. In vivo, YM58483/BTP2 (1 mg/kg) attenuated IL-17+ cell activation, inflammation, and severity of AKI following either I/R or intramuscular glycerol injection. Rats treated with high-salt diet (5-9 weeks after I/R) manifested progressive disease indicated by enhanced inflammation, fibrosis, and impaired renal function. These responses were significantly attenuated by YM58483/BTP2. In peripheral blood of critically ill patients, Orai1+ cells were significantly elevated by approximately 10-fold and Th17 cells were elevated by approximately 4-fold in AKI versus non-AKI patients. Further, in vitro stimulation of CD4+ cells from AKI patients increased IL-17, which was blocked by SOCE inhibitors. These data suggest that Orai1 SOCE is a potential therapeutic target in AKI and CKD progression

    Food Demand Projections Using Full Demand Systems

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    Disaggregated food demand projections for developing countries, although essential for improved development planning and effective policy making, are rare. Moreover food demand projection models are usually based on aggregated, national-level data. In this article, under conditions of weak separability and multistage budgeting decisions, a structural model capable fo generating regional-level food demand projections for a disaggregated set of commodities is developed and estimated using data from an Indonesian expenditure survey. Regional food demand projections in Indonesia obtain under a scenario assuming constant real prices are then combines into national-level estimates.

    Time of your hate: The challenge of time in hate speech detection on social media

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    The availability of large annotated corpora from social media and the development of powerful classification approaches have contributed in an unprecedented way to tackle the challenge of monitoring users' opinions and sentiments in online social platforms across time. Such linguistic data are strongly affected by events and topic discourse, and this aspect is crucial when detecting phenomena such as hate speech, especially from a diachronic perspective. We address this challenge by focusing on a real case study: the "Contro l'odio" platform for monitoring hate speech against immigrants in the Italian Twittersphere. We explored the temporal robustness of a BERT model for Italian (AlBERTo), the current benchmark on non-diachronic detection settings. We tested different training strategies to evaluate how the classification performance is affected by adding more data temporally distant from the test set and hence potentially different in terms of topic and language use. Our analysis points out the limits that a supervised classification model encounters on data that are heavily influenced by events. Our results show how AlBERTo is highly sensitive to the temporal distance of the fine-tuning set. However, with an adequate time window, the performance increases, while requiring less annotated data than a traditional classifier

    Inhibition of inducible Nitric Oxide Synthase expression by an acetonic extract from Feijoa sellowiana Berg. fruits.

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    Feijoa sellowiana Berg. fruits and especially the acetonic extract have been shown to possess biological activities, although the responsible compounds have never been identified. The present study was designed to evaluate the anti-inflammatory activity of an acetonic extract from F. sellowiana Berg. fruits on the nitric oxide (NO) pathway, which plays an important role in inflammation. To this aim the J774 cell line, which expresses inducible nitric oxide synthase (iNOS) following stimulation with lipopolysaccharide (LPS), has been utilized, and the effects of this extract and its fractions on NO production, iNOS protein expression, and signal pathways involved in its regulation have been evaluated. This study demonstrates that at least some part of the anti-inflammatory activity of the acetonic extract is due to the suppression of NO production by flavone and stearic acid. The mechanism of this inhibition seems to be related to an action on the expression of the enzyme iNOS through the attenuation of nuclear factor κB (NF-κB) and/or mitogen-activated protein kinase (MAPK) activation

    Economic Equity and the Food Stamp Program

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    The Thrifty Food Plan (TFP) is used to estimate the household food cost used for determining benefits for participants in the food stamp program. Dietary norms and requirements for macro and micronutrients are reflected in the TFP. Because the TFP is important in calculating benefit levels for FSP participants, it has received broad attention in policy debate. The present analysis shows that household food costs quite similar to those from the TFP can be calculated directly from available USDA Nationwide Food Consumption Survey data. The method developed and applied is simpler and more specialized to household by size and composition than the TFP. Also, it does not use dietary requirements. The new approach has a sound foundation in economics and could result in a more equitable distribution of food stamp program benefits

    Renal endothelial dysfunction in acute kidney ischemia reperfusion injury

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    Acute kidney injury is associated with alterations in vascular tone that contribute to an overall reduction in GFR. Studies in animal models indicate that ischemia triggers alterations in endothelial function that contribute significantly to the overall degree and severity of a kidney injury. Putative mediators of vasoconstriction that may contribute to the initial loss of renal blood flow and GFR are highlighted. In addition, there is discussion of how intrinsic damage to the endothelium impairs homeostatic responses in vascular tone as well as promotes leukocyte adhesion and exacerbating the reduction in renal blood flow. The timing of potential therapies in animal models as they relate to the evolution of AKI, as well as the limitations of such approaches in the clinical setting are discussed. Finally, we discuss how acute kidney injury induces permanent alterations in renal vascular structure. We posit that the cause of the sustained impairment in kidney capillary density results from impaired endothelial growth responses and suggest that this limitation is a primary contributing feature underlying progression of chronic kidney disease
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