Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

A Comparative Risk Assessment Of Burden Of Disease And Injury Attributable To 67 Risk Factors And Risk Factor Clusters In 21 Regions, 1990–2010: A Systematic Analysis For The Global Burden Of Disease Study 2010

Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time

Luminescence properties of magnesium phosphate glass doped samarium

Samarium doped magnesium phosphate glass having a composition of [P 2O 5] 50-x-[MgO] 50-[Sm 2O 3] x, with 0≤:x≤:4 mol% were prepared by melt-quenching method. The emission spectra were recorded using the photoluminescence spectrometer in the range of 540-730 nm at room temperature after being excited at 403 nm. It was found that the emission spectrum of Sm 3+consisted of four emission bands at ∼559.76 nm, ∼597.32 nm, ∼641.55 nm and ∼705.57 nm which were assign as a transition of 4G 5/2→ 6H 5/2, 4G 5/2 → 6H 7/2, 4G 5/2→ 6H 9/2 and 4G 5/2→ 6H 11/2 respectively. The transition of 4G 5/2→ 6H 7/2 is detected as the strongest orange (597.32 nm) luminescence peaks thus dominates the transition

Antibacterial effect of total 20 selected <i>Lactobacillus Spp</i>. against pathogens bacteria.

<p>Antibacterial effect of total 20 selected <i>Lactobacillus Spp</i>. against pathogens bacteria.</p

Inhibition of secreted IL-8 of selected <i>Lactobacillus</i> isolates.

<p>These isolates were selected based on their significant activities found in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144467#pone.0144467.g004" target="_blank">4</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144467#pone.0144467.g005" target="_blank">5</a>. The results are reported as the mean ± SD of triplicate samples. Mean comparison was done with unpaired t-test. * & ** indicate statistically significant difference p<0.05 and p<0.001, respectively, for reduction of IL-8 production by lactobacilli isolates in HT-29 cell line stimulated with LPS.</p

Effect of selected <i>Lactobacillus</i> sp. on myeloperoxidase (MPO) activity, disease activity index (DAI) and colon length, on DSS-induced colitis.

<p>Mean comparison was done with unpaired t-test. ** Highly significantly different from DSS group at P <0.01. *Significantly different from DSS group at P < 0.05.</p

Genotypic clustering of isolated <i>Lactobacillus sp</i>. with RAPD PCR assay.

<p>Genotypic clustering of isolated <i>Lactobacillus sp</i>. with RAPD PCR assay.</p