A whole-blood transcriptome meta-analysis identifies gene expression signatures of cigarette smoking

Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a metaanalysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) < 0.1, we identified 1270 differentially expressed genes in current vs. never smokers, and 39 genes in former vs. never smokers. Expression levels of 12 genes remained elevated up to 30 years after smoking cessation, suggesting that the molecular consequence of smoking may persist for decades. Gene ontology analysis revealed enrichment of smoking-related genes for activation of platelets and lymphocytes, immune response, and apoptosis. Many of the top smoking-related differentially expressed genes, including LRRN3 and GPR15, have DNA methylation loci in promoter regions that were recently reported to be hypomethylated among smokers. By linking differential gene expression with smoking-related disease phenotypes, we demonstrated that stroke and pulmonary function show enrichment for smoking-related gene expression signatures. Mediation analysis revealed the expression of several genes (e.g. ALAS2) to be putative mediators of the associations between smoking and inflammatory biomarkers (IL6 and C-re

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Psychopathy among prisoners in England and Wales

Most research into psychopathy among prisoners is based on selected samples. It remains unclear whether prevalences are lower among European populations. This study aimed to measure the prevalence of psychopathy, and the distribution and correlates of psychopathic traits in a representative national sample of prisoners. Psychopathy was measured using the revised Psychopathy Checklist (PCL-R) in a second stage, cross-sectional survey of prisoners in England and Wales in 1997 (n = 496). Poisson regression analysis was carried out to examine independent associations between correlates and PCL-R total and factor scores. The prevalence of categorically diagnosed psychopathy at a cut off of 30 was 7.7% (95%CI 5.2–10.9) in men and 1.9% (95%CI 0.2–6.9) in women. Psychopathic traits were less prevalent among women. They were correlated with younger age, repeated imprisonment, detention in higher security, disciplinary infractions, antisocial, narcissistic, histrionic, and schizoid personality disorders, and substance misuse, but not neurotic disorders or schizophrenia. The study concluded that psychopathy and psychopathic traits are prevalent among male prisoners in England and Wales but lower than in most previous studies using selected samples. However, most correlates with psychopathic traits were similar to other studies. Psychopathy identifies the extreme of a spectrum of social and behavioral problems among prisoners

Exploration of shared genetic architecture between subcortical brain volumes and anorexia nervosa

In MRI scans of patientswith anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknownwhether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlyingAN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlationsrangedfrom-0.10to0.23(allp > 0.05). Thereweresomesigns ofaninverseconcordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [ 0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune systemrelevant genes, in particularDRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain-and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN.Stress-related psychiatric disorders across the life spa

Sensitivity of Ozone Concentrations to Rate Constants in a Modified SAPRC90 Chemical Mechanism Used for Canadian Lower Fraser Valley Ozone Studies

The SAPRC90 chemical mechanism implemented in CALGRID is modified and updated for the specific emissions and applications of the Lower Fraser Valley (LFV) of British Columbia, Canada. Explicit reactions related to biogenic emissions and alternative fuels are added. The sensitivity of ozone formation to rate parameters in the mechanism is determined for an episode specific trajectory which originates under relatively clean marine conditions and passes over the urban core of Vancouver during the morning rush hour. Of the 137 reactions in the modified mechanism, the rate constants of 44 reactions are found to have a high sensitivity on ozone formation. The 44 reactions are further divided into general sensitive reactions, for which rate constant changes near the base case values have observable effects on maximum ozone concentrations, and limit-sensitive reactions, for which rate constant changes of more than an order of magnitude are required to have an observable impact on ozone concentrations. For the sensitive reactions, both ozone sensitivity coefficients for small changes (20%) in the rate constants and effects on ozone caused by large rate constant changes (factors of 0, 0.5, and 2) are calculated. Of note is the importance of several photolysis reactions and the reactions of OH with a class of reactive aromatics, including xylenes, on ozone concentrations in the LFV

A radioanalytical scheme for determining transuranic nuclides and90Sr in environmental samples

A method is described incorporating the procedures used in the radiochemical assay of Pu, Am and radiostrontium in environmental samples into a single radioanalytical sequential scheme. Sequential schemes have been used for determining the transuranic nuclides (isotopes of Pu and Am) in various types of sample matrices, but do not normally incorporate90Sr within the same scheme. The method offers potential savings in analyst time and reagents for the analyses of these nuclides, and is particularly suitable for small analytical laboratories where manpower resources coupled with a limited working time (8-hour working day) are constraints, and where limited amounts of sample are submitted for the analyses of all 3 radionuclides

Distribution of radiocaesium in the soil-plant systems of upland areas of Europe

The distribution and behavior of Cs in the soil-plant systems at some upland sites in Northeastern Italy, Scotland, and Norway have been investigated. From the limited range of samples taken, there appears to be no dominant physicochemical control on the plant availability of Cs. The presence of micaceous minerals or illitic clays does not significantly inhibit Cs uptake, either because of recycling in the organic surface horizons or because of clay-organic complex formation. Lower plants (bryophytes and lichens) show the highest Cs accumulation. Of the higher plants, ericaceous species take up Cs more than the others

The relationship between concentrations of plutonium and americium in soil interstitial waters and their uptake by plants

Large soil cores (23.5 cm diameter), containing elevated concentrations of plutonium and americium derived from fuel reprocessing effluents (typically 2000–3000 but up to 10000 Bq kg−1 239,240Pu and 3000–5000 but up to 15 000 Bq kg−1 241Am), were collected from three zones of a salt marsh in west Cumbria. The standing vegetation was removed, the cores placed in a greenhouse and the vegetation allowed to regrow. After 2 months, the regrowth was harvested and the amount of plutonium and americium taken up determined. These data, combined with data from earlier, in-situ sampling of soil pore waters and from analysis of soil cores, allow estimation of soil-plant transfers. If these are expressed simply as the ratio of the activity concentrations in the plant tissues to those in the soil, the values lie in the range 10−5−10−6, comparable to those found by many other workers. However, the ratio of concentrations in plant tissues to those in the soil solution is much higher; 40–110 l kg−1 for 239,240Pu and 210–640 l kg−1 for 241Am. There appears to be a consistent relationship between soil-plant transfer and the in-situ solid-solution distribution coefficient (Rd)