13 research outputs found
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OX40 signaling favors the induction of TH9 cells and airway inflammation
The mechanisms regulating T helper 9 (TH9) cells and TH9-mediated diseases remain poorly defined. Here, we demonstrate that the receptor OX40 (Tnfrsf4) is a powerful inducer of TH9 cells in vitro and TH9-dependent airway inflammation in vivo. Under TGF-β based polarizing conditions, OX40 ligation eliminated production of induced regulatory T cells and TH17 cells, and divertedCD4+Foxp3− T cells to a TH9 phenotype. Mechanistically, OX40 activated the ubiquitin ligase TRAF6, which triggered the induction of NF-kB-inducing kinase (NIK) in CD4+ T cells and the non-canonical NF-kB pathway which subsequently lead toTH9 generation. Thus, our study identifies a previously unknown mechanism of TH9 induction and may have important clinical implications in allergic inflammation
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Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W
Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl−/HCO−3 exchanger, SLC26A3. We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA-SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent) intracellular distribution. The WT protein is similarly localized in LLC-PK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting
Anodic oxidation of aryl propargyl and aryl allyl ethers at a platinum electrode
The oxidation reactions of aromatic 3,3-sigmatropic systems have been investigated under different conditions viz., (a) anodic oxidation in amphipr Oxidation reactions of aromatic 3,3-sigmatropic systems have been investigated under different conditions
Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation
Tim-1, a phosphatidylserine receptor expressed on B cells, induces interleukin 10 (IL-10) production by sensing apoptotic cells. Here we show that mice with B cell-specific Tim-1 deletion develop tissue inflammation in multiple organs including spontaneous paralysis with inflammation in the central nervous system (CNS). Transcriptomic analysis demonstrates that besides IL-10, Tim-1+ B cells also differentially express a number of co-inhibitory checkpoint receptors including TIGIT. Mice with B cell-specific TIGIT deletion develop spontaneous paralysis with CNS inflammation, but with limited inflammation in other organs. Our findings suggest that Tim-1+ B cells are essential for maintaining self-tolerance and restraining tissue inflammation, and that Tim-1 signaling-dependent TIGIT expression on B cells is essential for maintaining CNS-specific tolerance. A possible critical role of aryl hydrocarbon receptor (AhR) in regulating the B cell function is discussed, as we find that AhR is among the preferentially expressed transcription factors in Tim-1+ B cells and regulates their TIGIT and IL-10 expression
Radiant frost tolerance in pulse crops-a review
Radiant frost is a major abiotic stress, and one of the principal limiting factors for agricultural production worldwide, including Australia. Legumes, including field pea, faba bean, lentil and chickpea, are very sensitive to chilling and freezing temperatures, particularly at the flowering, early pod formation and seed filling stages. Radiant frost events occur when plants and soil absorb the sunlight during the day time and radiate heat during the night when the sky is clear and the air is still. Dense chilled air settles into the lowest areas of the canopy, where the most serious frost damage occurs. The cold air causes nucleation of the intracellular fluid in plant tissues and the subsequent rupturing of the plasma membrane. Among the cool season grain legume crops, chickpea, lentil and faba bean and field pea are the most susceptible to radiant frost injury during the reproductive stages. The more sensitive stages are flowering and podding. Frost at the reproductive stage results in flower abortion, poor pod set and impaired pod filling, leading to a drastic reduction in yield and quality. In contrast, in the UK and European countries, frost stress is related to the vegetative stages and, in particular, the effects of frost have been studied on cotyledon, uni/tri-foliolate leaf and seedling stages during the first few weeks of growth. Few winter genotypes have been identified as frost tolerant at vegetative stages. Vegetative frost tolerance is not related to reproductive frost tolerance, and hybrids from the vegetative frost-tolerant genotypes may not necessarily be tolerant at the reproductive stage. Tolerance to radiant frost has an inverse relationship with plant age. In the field, frost tolerance decreases from the vegetative stage to reproductive stage. Unlike wheat and barley, it is difficult to analyse and score frost damage in grain legume crops due to the presence of various phenophases on one plant at the reproductive stage. The extent of frost damage depends on the specific phenophases on a particular plant. However, current studies on genetic transformation of cold tolerant gene(s), membrane modifications, anti-freeze substances and ice nucleating or inhibiting agents provide useful information to improve our current understanding on frost damage and related mechanisms. The effects of frost damage on yield and grain quality illustrate the significance of this area of research. This review discusses the problem of radiant frost damage to cool season legumes in Australia and the associated research that has been carried out to combat this problem locally and worldwide. The available literature varies between species, specific climatic conditions and origin.Ahmad Maqbool, Shaista Shafiq and Lachlan Lak