The effects of an insertion in the 5 ' UTR of the AMCase on gene expression and pulmonary functions

Cataloged from PDF version of article.Background: Studies regarding the physiological role of acidic mammalian chitinase (AMCase) and the effects of its genetic variants on asthma have produced conflicting results. Objectives: We aimed to determine the genetic variants in the AMCase gene that could regulate the gene expression and thus influence disease severity. Methods: Genetic variants of the AMCase gene were determined by sequencing of asthmatics and healthy controls in up to -1 kb in the promoter region and exon 1 and 2. In an association study, a population of asthmatic (n = 504) and healthy Turkish children (n = 188) were genotyped for the observed SNPs. A replication study was performed in a North American adult population of patients with mild (n = 317) and severe (n = 145) asthma. The functional properties of the insertion were determined by promoter reporter assay, electromobility shift assay and transcription factor ELISA experiments. Results: Of the identified SNPs, only a ten base pair insertion (CAATCTAGGC) in the 5'UTR region of exon 2 was significantly associated with lower FEV(1) (beta = -14.63 SE = 6.241, P = 0.019) in Turkish children with asthma. However, in the adult population, the same insertion showed a trend toward higher FEV(1). The insertion was shown to have enhancer activity and the mutant probe possessing the insertion had higher binding affinity for the nuclear extracts. Conclusion: Our study shows that a ten base pair insertion in the 5'UTR region of AMCase gene may modify gene expression and thus may affect the severity of asthma. However, its effects appear to be different in different populations. (C) 2011 Elsevier Ltd. All rights reserved

Collection of Aerosolized Human Cytokines Using Teflon® Filters

Background: Collection of exhaled breath samples for the analysis of inflammatory biomarkers is an important area of research aimed at improving our ability to diagnose, treat and understand the mechanisms of chronic pulmonary disease. Current collection methods based on condensation of water vapor from exhaled breath yield biomarker levels at or near the detection limits of immunoassays contributing to problems with reproducibility and validity of biomarker measurements. In this study, we compare the collection efficiency of two aerosol-to-liquid sampling devices to a filter-based collection method for recovery of dilute laboratory generated aerosols of human cytokines so as to identify potential alternatives to exhaled breath condensate collection. Methodology/Principal Findings: Two aerosol-to-liquid sampling devices, the SKC® Biosampler and Omni 3000™, as well as Teflon® filters were used to collect aerosols of human cytokines generated using a HEART nebulizer and single-pass aerosol chamber setup in order to compare the collection efficiencies of these sampling methods. Additionally, methods for the use of Teflon® filters to collect and measure cytokines recovered from aerosols were developed and evaluated through use of a high-sensitivity multiplex immunoassay. Our results show successful collection of cytokines from pg/m3 aerosol concentrations using Teflon® filters and measurement of cytokine levels in the sub-picogram/mL concentration range using a multiplex immunoassay with sampling times less than 30 minutes. Significant degradation of cytokines was observed due to storage of cytokines in concentrated filter extract solutions as compared to storage of dry filters. Conclusions: Use of filter collection methods resulted in significantly higher efficiency of collection than the two aerosol-to-liquid samplers evaluated in our study. The results of this study provide the foundation for a potential new technique to evaluate biomarkers of inflammation in exhaled breath samples

Search for light resonances decaying to boosted quark pairs and produced in association with a photon or a jet in proton–proton collisions at √s=13 TeV with the ATLAS detector

This Letter presents a search for new light resonances decaying to pairs of quarks and produced in association with a high-pT photon or jet. The dataset consists of proton–proton collisions with an integrated luminosity of 36.1 fb−1at a centre-of-mass energy of √s=13TeV recorded by the ATLAS detector at the Large Hadron Collider. Resonance candidates are identified as massive large-radius jets with substructure consistent with a particle decaying into a quark pair. The mass spectrum of the candidates is examined for local excesses above background. No evidence of a new resonance is observed in the data, which are used to exclude the production of a lepto-phobic axial-vector Z boson

Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype

Objective: The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. Methods: This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima - media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Results: Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Conclusion: Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins