Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation.

A plethora of functional and genetic studies have suggested a key role for the IL-23 pathway in chronic intestinal inflammation. Currently, pathogenic actions of IL-23 have been ascribed to specific effects on immune cells. Herein, we unveil a protective role of IL-23R signaling. Mice deficient in IL-23R expression in intestinal epithelial cells (Il23R(ΔIEC)) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23R(ΔIEC) mice show impaired mucosal IL-22 induction in response to IL-23. αThy-1 treatment significantly deteriorates colitis in Il23R(ΔIEC) animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23R(ΔIEC) mice by recruiting neutrophils as IL-22-producing cells, thereby restoring mucosal IL-22 levels. The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells.This work was supported by DFG Excellence Cluster Inflammation at Interfaces; the SFB877 B9, the SFB 1182 C2 project, and the BMBF IHEC DEEP project TP2.3 and 5.2 (to P.R.); the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007- 2013)/ERC grant agreement 260961 (to A.K.); the National Institute for Health Research Cambridge Biomedical Research Centre, ERC CoG GA 648889, and WTIA 106260-Z-14-Z (to A.K.); NIH DK53056, DK44319, and DK088199 (to R.S.B.); and the Fondation pour la Recherche Medicale (to M.C.).This is the final version of the article. It first appeared from Cell/Elsevier via http://dx.doi.org/10.1016/j.celrep.2016.07.05

Spousal involvement and CPAP adherence: A dyadic perspective

Poor adherence to continuous positive airway pressure (CPAP) treatment is associated with substantial health care costs, morbidity and mortality, and has been a leading obstacle in the effective management of obstructive sleep apnea (OSA). Successful interventions to improve CPAP adherence may ultimately include a variety of components. For patients living with spouses (refers to all domestic partners), the spouse will likely be an integral component to any successful intervention. Developing understanding of the role of spouses in adherence to CPAP has been identified to be a critical research need. This review expands the investigation of CPAP adherence to a broader context, from an exclusive focus on individual patients to a dyadic perspective encompassing both patients and their spouses. A conceptual framework based on social support and social control theories is proposed to understand spousal involvement in CPAP adherence. Methodologies for future investigations are discussed, along with implications for developing interventions that engage both patients and their spouses to improve CPAP use

A compact IGBT driver for high temperature applications

This paper describes the basic principles and experimental results of a compact IGBT gate driver for high temperature applications. The presented concept is especially dedicated to IGBT drivers which must provide high galvanic insulation at high ambient temperatures. In contrast to other well known approaches, the new concept is well suited for designs of very small size and with high insulation voltage. This makes these drivers an optimum solution for any kind of mechatronic system integration. The use of a special ferrite material with a Curie temperature far above the maximum ambient temperature and a consistent renunciation of temperature critical devices like electrolytic capacitors ensures a reliable operation up to ambient temperatures of 125°C. The high operating temperature, the noise immunity and the very small size make the new driver ideally suitable for a mechatronic integration into power semiconductor modules

Les échos de phonons

Echo experiments performed on non-centrosymmetric single crystals are interpreted in terms of phonon echoes. The role of acoustic waves is demonstrated experimentally. The principles which explain these experiments are very similar to those which govern the phenomenon of spin echoes. Time reversal is due to a non linear interaction between the electric field and the elastic waves. The relaxation time T 1 of the energy and T2 of phonon population coherence are defined and have been measured in various crystals. A few ideas for the future development of this type of experiments are considered.Des expériences d'échos sur des cristaux non centrosymétriques sont interprétées en termes d'échos de phonons. Le rôle des ondes acoustiques est démontré expérimentalement. Les principes qui expliquent ces expériences sont très analogues à ceux qui gouvernent le phénomène d'échos de spin. Le renversement du temps est assuré par une interaction non linéaire entre champ électrique et ondes élastiques. Les temps de relaxation T1 relatif à l'énergie et T 2 relatif à la cohérence d'une population de phonons sont définis et mesurés. Quelques perspectives pour le développement de ce type d'expériences sont esquissées

Analysis of NOD2-mediated proteome response to muramyl dipeptide in HEK293 cells

NOD2, a cytosolic receptor for the bacterial proteoglycan fragment muramyl dipeptide (MDP), plays an important role in the recognition of intracellular pathogens. Variants in the bacterial sensor domain of NOD2 are genetically associated with an increased risk for the development of Crohn disease, a human chronic inflammatory bowel disease. In the present study, global protein expression changes after MDP stimulation were analyzed by two-dimensional PAGE of total protein extracts of human cultured cells stably transfected with expression constructs encoding for wild type NOD2 (NOD2(WT)) or the disease-associated NOD2 L1007fsinsC (NOD2(SNP13)) variant. Differentially regulated proteins were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) peptide mass fingerprinting and MALDI MS/MS. The limited overlap in the responses of the NOD2-overexpressing cell lines to MDP included a down-regulation of heat shock 70-kDa protein 4. A complex pro-inflammatory program regulated by NOD2(WT) that encompasses a regulation of key genes involved in protein folding, DNA repair, cellular redox homeostasis, and metabolism was observed both under normal growth conditions and after stimulation with MDP. By using the comparison of NOD2(WT) and disease-associated NOD2(SNP13) variant, we have identified a proteomic signature pattern that may further our understanding of the influence of genetic variations in the NOD2 gene in the pathophysiology of chronic inflammatory bowel disease