Traffic-related pollution and asthma prevalence in children. Quantification of associations with nitrogen dioxide.

Ambient nitrogen dioxide is a widely available measure of traffic-related air pollution and is inconsistently associated with the prevalence of asthma symptoms in children. The use of this relationship to evaluate the health impact of policies affecting traffic management and traffic emissions is limited by the lack of a concentration-response function based on systematic review and meta-analysis of relevant studies. Using systematic methods, we identified papers containing quantitative estimates for nitrogen dioxide and the 12 month period prevalence of asthma symptoms in children in which the exposure contrast was within-community and dominated by traffic pollution. One estimate was selected from each study according to an a priori algorithm. Odds ratios were standardised to 10 μg/m(3) and summary estimates were obtained using random- and fixed-effects estimates. Eighteen studies were identified. Concentrations of nitrogen dioxide were estimated for the home address (12) and/or school (8) using a range of methods; land use regression (6), study monitors (6), dispersion modelling (4) and interpolation (2). Fourteen studies showed positive associations but only two associations were statistically significant at the 5 % level. There was moderate heterogeneity (I(2) = 32.8 %) and the random-effects estimate for the odds ratio was 1.06 (95 % CI 1.00 to 1.11). There was no evidence of small study bias. Individual studies tended to have only weak positive associations between nitrogen dioxide and asthma prevalence but the summary estimate bordered on statistical significance at the 5 % level. Although small, the potential impact on asthma prevalence could be considerable because of the high level of baseline prevalence in many cities. Whether the association is causal or indicates the effects of a correlated pollutant or other confounders, the estimate obtained by the meta-analysis would be appropriate for estimating impacts of traffic pollution on asthma prevalence

Intramolecular Folding in Human ILPR Fragment with Three C-Rich Repeats

Enrichment of four tandem repeats of guanine (G) rich and cytosine (C) rich sequences in functionally important regions of human genome forebodes the biological implications of four-stranded DNA structures, such as G-quadruplex and i-motif, that can form in these sequences. However, there have been few reports on the intramolecular formation of non-B DNA structures in less than four tandem repeats of G or C rich sequences. Here, using mechanical unfolding at the single-molecule level, electrophoretic mobility shift assay (EMSA), circular dichroism (CD), and ultraviolet (UV) spectroscopy, we report an intramolecularly folded non-B DNA structure in three tandem cytosine rich repeats, 5'-TGTC4ACAC4TGTC4ACA (ILPR-I3), in the human insulin linked polymorphic region (ILPR). The thermal denaturation analyses of the sequences with systematic C to T mutations have suggested that the structure is linchpinned by a stack of hemiprotonated cytosine pairs between two terminal C4 tracts. Mechanical unfolding and Br2 footprinting experiments on a mixture of the ILPR-I3 and a 5′-C4TGT fragment have further indicated that the structure serves as a building block for intermolecular i-motif formation. The existence of such a conformation under acidic or neutral pH complies with the strand-by-strand folding pathway of ILPR i-motif structures

Global lung function initiative 2012 reference values for spirometry in Asian Americans

Background Spirometry reference values specifically designed for Asian Americans are currently unavailable. The performance of Global Lung Function Initiative 2012 (GLI-2012) equations on assessing spirometry in Asian Americans has not been evaluated. This study aimed to assess the fitness of relevant GLI-2012 equations for spirometry in Asian Americans. Methods Asian subjects who never smoked and had qualified spirometry data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Z-scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were separately constructed with GLI-2012 equations for North East (NE) Asians, South East (SE) Asians, and individuals of mixed ethnic origin (Mixed). In addition, Proportions of subjects with observed spirometry data below the lower limit of normal (LLN) were also evaluated on each GLI-2012 equation of interest. Results This study included 567 subjects (250 men and 317 women) aged 6–79 years. Spirometry z-scores (z-FEV1, z-FVC, and z-FEV1/FVC) based on GLI-2012 Mixed equations had mean values close to zero (− 0.278 to − 0.057) and standard deviations close to one (1.001 to 1.128); additionally, 6.0% (95% confidence interval (CI) 3.1–8.9%) and 6.4% (95% CI 3.7–9.1%) of subjects were with observed data below LLN for FEV1/FVC in men and women, respectively. In contrast, for NE Asian equations, all mean values of z-FEV1 and z-FVC were smaller than − 0.5; for SE Asian equations, mean values of z-FEV1/FVC were significantly smaller than zero in men (− 0.333) and women (− 0.440). Conclusions GLI-2012 equations for individuals of mixed ethnic origin adequately fitted spirometry data in this sample of Asian Americans. Future studies with larger sample sizes are needed to confirm these findings

Genomic Analysis of Parent-of-Origin Allelic Expression in Arabidopsis thaliana Seeds

Differential expression of maternally and paternally inherited alleles of a gene is referred to as gene imprinting, a form of epigenetic gene regulation common to flowering plants and mammals. In plants, imprinting primarily occurs in the endosperm, a seed tissue that supports the embryo during its growth and development. Previously, we demonstrated that widespread DNA demethylation at remnants of transposable elements accompanies endosperm development and that a subset of these methylation changes are associated with gene imprinting. Here we assay imprinted gene expression genome-wide by performing high-throughput sequencing of RNA derived from seeds of reciprocal intraspecific crosses. We identify more than 200 loci that exhibit parent-of-origin effects on gene expression in the endosperm, including a large number of transcription factors, hormone biosynthesis and response genes, and genes that encode regulators of epigenetic information, such as methylcytosine binding proteins, histone methyltransferases, and chromatin remodelers. The majority of these genes are partially, rather than completely, imprinted, suggesting that gene dosage regulation is an important aspect of imprinted gene expression

Electrophysiological evidence of enhanced performance monitoring in recently abstinent alcoholic men

RATIONALE: Chronic alcoholism is associated with mild to moderate cognitive impairment. Under certain conditions, impairment can be ameliorated by invoking compensatory processes. OBJECTIVE: To identify electrophysiological mechanisms of such compensation that would be required to resolve response conflict. METHODS: 14 abstinent alcoholic men and 14 similarly aged control men performed a variation of the Eriksen flanker task during an electroencephalography (EEG) recording to examine whether alcoholics could achieve and maintain control-level performance and whether EEG markers could identify evidence for the action of compensatory processes in the alcoholics. Monitoring processes engaged following a response were indexed by the correct related negativity (CRN) and error related negativity (ERN), two medial-frontal negative event-related potentials. RESULTS: The alcoholics were able to perform at control levels on accuracy and reaction time (RT). Alcoholics generated larger ERN amplitudes following incorrect responses and larger CRNs following correct responses than controls. Both groups showed evidence of post-error slowing. Larger CRN amplitudes in the alcoholics were related to longer RTs. Also observed in the alcoholics was an association between smaller CRN amplitudes and length of sobriety, suggesting a normalization of monitoring activity with extended abstinence. CONCLUSIONS: To the extent that greater amplitude of these electrophysiological markers of performance monitoring indexes greater resource allocation and performance compensation, the larger amplitudes observed in the alcoholic than control group support the view that elevated performance monitoring enables abstinent alcoholics to overcome response conflict, as was evident in their control-level performance

DNA Methylation Causes Predominant Maternal Controls of Plant Embryo Growth

The parental conflict hypothesis predicts that the mother inhibits embryo growth counteracting growth enhancement by the father. In plants the DNA methyltransferase MET1 is a central regulator of parentally imprinted genes that affect seed growth. However the relation between the role of MET1 in imprinting and its control of seed size has remained unclear. Here we combine cytological, genetic and statistical analyses to study the effect of MET1 on seed growth. We show that the loss of MET1 during male gametogenesis causes a reduction of seed size, presumably linked to silencing of the paternal allele of growth enhancers in the endosperm, which nurtures the embryo. However, we find no evidence for a similar role of MET1 during female gametogenesis. Rather, the reduction of MET1 dosage in the maternal somatic tissues causes seed size increase. MET1 inhibits seed growth by restricting cell division and elongation in the maternal integuments that surround the seed. Our data demonstrate new controls of seed growth linked to the mode of reproduction typical of flowering plants. We conclude that the regulation of embryo growth by MET1 results from a combination of predominant maternal controls, and that DNA methylation maintained by MET1 does not orchestrate a parental conflict

Does respiratory health contribute to the effects of long-term air pollution exposure on cardiovascular mortality?

BACKGROUND: There is growing epidemiological evidence that short-term and long-term exposure to high levels of air pollution may increase cardiovascular morbidity and mortality. In addition, epidemiological studies have shown an association between air pollution exposure and respiratory health. To what extent the association between cardiovascular mortality and air pollution is driven by the impact of air pollution on respiratory health is unknown. The aim of this study was to investigate whether respiratory health at baseline contributes to the effects of long-term exposure to high levels of air pollution on cardiovascular mortality in a cohort of elderly women. METHOD: We analyzed data from 4750 women, aged 55 at the baseline investigation in the years 1985–1994. 2593 of these women had their lung function tested by spirometry. Respiratory diseases and symptoms were asked by questionnaire. Ambient air pollution exposure was assessed by the concentrations of NO(2 )and total suspended particles at fixed monitoring sites and by the distance of residency to a major road. A mortality follow-up of these women was conducted between 2001 and 2003. For the statistical analysis, Cox' regression was used. RESULTS: Women with impaired lung function or pre-existing respiratory diseases had a higher risk of dying from cardiovascular causes. The impact of impaired lung function declined over time. The risk ratio (RR) of women with forced expiratory volume in one second (FEV(1)) of less than 80% predicted to die from cardiovascular causes was RR = 3.79 (95%CI: 1.64–8.74) at 5 years survival time and RR = 1.35 (95%CI: 0.66–2.77) at 12 years. The association between air pollution levels and cardiovascular death rate was strong and statistically significant. However, this association did only change marginally when including indicators of respiratory health into the regression analysis. Furthermore, no interaction between air pollution and respiratory health on cardiovascular mortality indicating a higher risk of those with impaired respiratory health could be detected. CONCLUSION: Respiratory health is a predictor for cardiovascular mortality. In women followed about 15 years after the baseline investigation at age 55 years long-term air pollution exposure and impaired respiratory health were independently associated with increased cardiovascular mortality

Contribution of smoking and air pollution exposure in urban areas to social differences in respiratory health

<p>Abstract</p> <p>Background</p> <p>Socio-economic status, smoking, and exposure to increased levels of environmental air pollution are associated with adverse effects on respiratory health. We assessed the contribution of occupational exposures, smoking and outdoor air pollution as competing factors for the association between socio-economic status and respiratory health indicators in a cohort of women from the Ruhr area aged 55 at the time of investigation between 1985 and 1990.</p> <p>Methods</p> <p>Data of 1251 women with spirometry and complete questionnaire information about respiratory diseases, smoking and potential confounders were used in the analyses. Exposure to large-scale air pollution was assessed with data from monitoring stations. Exposure to small-scale air pollution was assessed as traffic-related exposure by distance to the nearest major road. Socio-economic status was defined by educational level. Multiple regression models were used to estimate the contribution of occupational exposures, smoking and outdoor air pollution to social differences in respiratory health.</p> <p>Results</p> <p>Women with less than 10 years of school education in comparison to more than 10 years of school education were more often occupationally exposed (16.4% vs. 10.1%), smoked more often (20.3% vs. 13.9%), and lived more often close to major roads (26.0% vs. 22.9%). Long-term exposure to increased levels of PM₁₀was significantly associated with lower school education. Women with low school education were more likely to suffer from respiratory symptoms and had reduced lung function. In the multivariate analysis the associations between education and respiratory health attenuated after adjusting for occupational exposure, smoking and outdoor air pollution. The crude odds ratio for the association between the lung function indicator FEV₁less than 80% of predicted value and educational level (<10 years vs. >10 years of school education) was 1.83 (95% CI: 1.22–2.74). This changed to 1.56 (95% CI: 1.03–2.37) after adjusting for occupational exposure, smoking and outdoor air pollution.</p> <p>Conclusion</p> <p>We found an association between socio-economic status and respiratory health. This can partly be explained by living conditions indicated by occupational exposure, smoking behaviour and ambient air pollution. A relevant part of the social differences in respiratory health, however, remained unexplained.</p

Eye Development under the control of SRp55/B52-Mediated Alternative Splicing of eyeless

The genetic programs specifying eye development are highly conserved during evolution and involve the vertebrate Pax-6 gene and its Drosophila melanogaster homolog eyeless (ey). Here we report that the SR protein B52/SRp55 controls a novel developmentally regulated splicing event of eyeless that is crucial for eye growth and specification in Drosophila. B52/SRp55 generates two isoforms of eyeless differing by an alternative exon encoding a 60-amino-acid insert at the beginning of the paired domain. The long isoform has impaired ability to trigger formation of ectopic eyes and to bind efficiently Eyeless target DNA sequences in vitro. When over-produced in the eye imaginal disc, this isoform induces a small eye phenotype, whereas the isoform lacking the alternative exon triggers eye over-growth and strong disorganization. Our results suggest that B52/SRp55 splicing activity is used during normal eye development to control eye organogenesis and size through regulation of eyeless alternative splicing

I-Motif Structures Formed in the Human c-MYC Promoter Are Highly Dynamic–Insights into Sequence Redundancy and I-Motif Stability

The GC-rich nuclease hypersensitivity element III1 (NHE III1) of the c-MYC promoter largely controls the transcriptional activity of the c-MYC oncogene. The C-rich strand in this region can form I-motif DNA secondary structures. We determined the folding pattern of the major I-motif formed in the NHE III1, which can be formed at near-neutral pH. While we find that the I-motif formed in the four 3′ consecutive runs of cytosines appears to be the most favored, our results demonstrate that the C-rich strand of the c-MYC NHE III1 exhibits a high degree of dynamic equilibration. Using a trisubstituted oligomer of this region, we determined the formation of two equilibrating loop isomers, one of which contains a flipped-out cytosine. Our results indicate that the intercalative cytosine+–cytosine base pairs are not always necessary for an intramolecular I-motif. The dynamic character of the c-MYC I-motif is intrinsic to the NHE III1 sequence and appears to provide stability to the c-MYC I-motif