Adam33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers

<p>Abstract</p> <p>Background</p> <p>Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function. This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers. We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.</p> <p>Methods</p> <p>Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33. COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287). The control group had an FEV1/FVC ratio ≥ 70% and ppFEV₁≥ 80% (n = 311) despite ≥ 20 pack years of smoking. Logistic and linear regressions were used for the analysis. Age, sex, and smoking status were considered as potential confounders.</p> <p>Results</p> <p>Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007). Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25–75 (p values 0.001 – 0.02). S2 was associated with FEV1/FVC ratio (p < 0.05). The association between S1 and residual volume revealed a trend toward significance (p value < 0.07). Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.</p> <p>Conclusion</p> <p>Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers. Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD.</p

The development of highly potent and selective small molecule correctors of Z α1-antitrypsin misfolding

α1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant α1-antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z α1-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active α1-antitrypsin correctors

Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy

Nutrients cause grassland biomass to outpace herbivory

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk

Constructing meaning about the delinquency of young girls in public-housing neighbourhoods

UID/SOC/04647/2013 SFRH/BPD/116119/2016Rooted in the theoretical approaches of social ecology and in childhood studies, the Ph.D. research project on which this paper is based aimed to achieve a better understanding of children’s socialization processes in multi-problematic spaces, particularly concerning their involvement in violence and delinquency. A case study based on ethnographic research and child-centred methods was carried out in six public-housing neighbourhoods in Portugal, which were chosen because they had relatively high levels of social deprivation, violence and crime. The specificity of the social group under study—children aged from 6 to 12 years old—and their living conditions, led us to extend the data collected by trying to learn, from the girls, the reasoning and the meanings they assign to their own actions in daily social practices. The intention was to study the features of girls’ socialization in the field through their own accounts of their lives and to examine their perspectives on offending behaviours. The genderized process of social learning in delinquency identified in the girls’ conversation is an important variable, as familial and social experiences tend to facilitate their entry into delinquency. The transmission of delinquent values takes place essentially within the female family circle or via female peers, rather than from the influence of male individuals.authorsversionpublishe

Analyses and localization of pectin-like carbohydrates in cell wall and mucilage of the green alga Netrium digitus

The unicellular, simply shaped desmid Netrium digitus inhabiting acid bog ponds grows in two phases. Prior to division, the cell elongates at its central zone, whereas in a second phase, polar tip growth occurs. Electron microscopy demonstrates that Netrium is surrounded by a morphologically homogeneous cell wall, which lacks pores. Immunocytochemical and biochemical analyses give insight into physical wall properties and, thus, into adaptation to the extreme environment. The monoclonal antibodies JIM5 and JIM7 directed against pectic epitopes with different degrees of esterification label preferentially growing wall zones in Netrium. In contrast, 2F4 marks the cell wall only after experimental de-esterification. Electron energy loss spectroscopy reveals Ca-binding capacities of pectins and gives indirect evidence for the degree of their esterification. An antibody raised against Netrium mucilage is not only specific to mucilage but also recognizes wall components in transmission electron microscopy and dot blots. These results indicate a smooth transition between mucilage and the cell wall in Netrium

Shoulder hemiarthroplasty for fractures of the proximal humerus

Proximal humeral fractures were managed with primary hemiarthroplasty in 57 patients, 53 women (93%) and 4 men (7%) aged 51–87 years (mean 72.2). The mean follow-up period was 52 months (range 12–98), and the mean Constant score was 59.2 (range 38–76). Patients were very satisfied (n = 19); satisfied (n = 32) or dissatisfied with the outcome (n = 5). One patient required early revision surgery. Surgical treatment of three- and four-part fractures of the proximal humerus with hemiarthroplasty is a safe and effective approach, the outcome of which appears to be related to the quality of the anatomical reconstruction of the tuberosities

How useful are volunteers for visual biodiversity surveys? An evaluation of skill level and group size during a conservation expedition

The ability of volunteers to undertake different tasks and accurately collect data is critical for the success of many conservation projects. In this study, a simulated herpetofauna visual encounter survey was used to compare the detection and distance estimation accuracy of volunteers and more experienced observers. Experience had a positive effect on individual detection accuracy. However, lower detection performance of less experienced volunteers was not found in the group data, with larger groups being more successful overall, suggesting that working in groups facilitates detection accuracy of those with less experience. This study supports the idea that by optimizing survey protocols according to the available resources (time and volunteer numbers), the sampling efficiency of monitoring programs can be improved and that non-expert volunteers can provide valuable contributions to visual encounter-based biodiversity surveys. Recommendations are made for the improvement of survey methodology involving non-expert volunteers