Mouse Sphingosine Kinase 1a Is Negatively Regulated through Conventional PKC-Dependent Phosphorylation at S373 Residue

Sphingosine kinase is a lipid kinase that converts sphingosine into sphingosine-1-phosphate, an important signaling molecule with intracellular and extracellular functions. Although diverse extracellular stimuli influence cellular sphingosine kinase activity, the molecular mechanisms underlying its regulation remain to be clarified. In this study, we investigated the phosphorylation-dependent regulation of mouse sphingosine kinase (mSK) isoforms 1 and 2. mSK1a was robustly phosphorylated in response to extracellular stimuli such as phorbol ester, whereas mSK2 exhibited a high basal level of phosphorylation in quiescent cells regardless of agonist stimulation. Interestingly, phorbol ester-induced phosphorylation of mSK1a correlated with suppression of its activity. Chemical inhibition of conventional PKCs (cPKCs) abolished mSK1a phosphorylation, while overexpression of PKC alpha, a cPKC isoform, potentiated the phosphorylation, in response to phorbol ester. Furthermore, an in vitro kinase assay showed that PKC alpha directly phosphorylated mSK1a. In addition, phosphopeptide mapping analysis determined that the S373 residue of mSK1a was the only site phosphorylated by cPKC. Interestingly, alanine substitution of S373 made mSK1a refractory to the inhibitory effect of phorbol esters, whereas glutamate substitution of the same residue resulted in a significant reduction in mSK1a activity, suggesting the significant role of this phosphorylation event. Taken together, we propose that mSK1a is negatively regulated through cPKC-dependent phosphorylation at S373 residueopen

Management of eosinophilic esophagitis in children according to atopic status: A retrospective cohort in northeast of France

International audienceIntroduction: Most children with eosinophilic esophagitis (EoE) are atopic, but the impact of atopy on the remission and development of EoE is still unclear. The aim of our study was to determine the impact of atopy on remission of EoE and to describe allergy tests and the choice of treatment for a cohort of EoE children in France.Methods: All children diagnosed with EoE between January 2013 and June 2018 in the five pediatric centers in the northeast of France were included. Children were divided into two groups according to personal atopic disorders. Histological remission was defined on the basis of an eosinophilic count below 15 eosinophils per high-power field.Results: Among the 49 children included, 38 (78%) were atopic. Allergy tests were performed for 45 children (92%). Rates of sensitization were similar in both groups: 64% had food sensitization and 64% had aeroallergen sensitization. The most commonly attempted first-line therapy was with proton pump inhibitors (63%), followed by swallowed topical steroids (STS) (18%). First-line therapy was not associated with atopic status (P=0.88). Atopic children had a nonsignificant tendency for a higher remission rate after STS (55% vs. 0%, P=0.24) and a higher global remission rate (54% vs. 33%, P=0.18) compared with non-atopic children.Conclusion: Allergy testing is relevant in the majority of children with EoE whether or not they have atopic disorders. Atopy seems to be associated with better response to STS. Further studies are needed to determine whether atopic status determines histological response

Experimental investigation of wave tip variability of impacting waves

We present an experimental study on the variation in wave impact location and present a mechanism for the development of free surface instabilities on the wave crest for repeatable plunging wave impacts on a vertical wall. The existence of free surface instabilities on an impacting wave is well known, but their characteristics and formation mechanism are relatively unknown. The development of the global wave shape is measured using a visualization camera, whereas the local wave shape is measured with an accurate stereo-planar laser-induced fluorescence technique. A repeatable wave is generated with negligible system variability. The global wave behavior resembles that of a plunging breaker, with a gas pocket cross-sectional area defined by an ellipse of constant aspect ratio. The variability of the local wave profile increases significantly as it approaches the wall. The impact location varies by ∼0.5% of the wave height or more than a typical pressure sensor diameter. Additionally, the wave tip accelerates to a velocity of 1.5√gh0 compared to the global wave velocity of 1.2√gh0. The difference in impact location and velocity can result in a pressure variation of ∼25%. A mechanism for instability development is observed as the wave tip becomes thinner and elongates when it approaches the wall. A flapping liquid sheet develops that accelerates the wave tip locally and this triggers a spanwise Rayleigh–Taylor instability.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Multi Phase SystemsHydraulic Structures and Flood RiskFluid Mechanic

La santé en mangeant et en bougeant: Le guide nutrition pour les aidants des personnes âgées

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Livret d’accompagnement destiné aux professionnels de santé. La santé en mangeant et en bougeant. Le guide nutrition pour les aidants des personnes âgées et le guide nutrition à partir de 55 ans

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