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

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)

A comparison of two techniques to determine carbon-14 in environmental samples.

We have experience of two methods for the analysis of 14C in environmental samples and have used this experience to directly compare these two techniques. Nine vegetation samples and a sucrose standard were analyzed using the benzene synthesis and combustion techniques. The results obtained using both methods were in good agreement and show that 14C data obtained using either technique are comparable. The analytical requirements for the two techniques vary considerably. In choosing a technique, a variety of factors such as sensitivity, sampl e size, sample type, carbon content and how the results are to be expressed, need to be considered

Plutonium in estuarine sediments and the associated interstitial waters

Nine pairs (three different depths in each of three different zones) of porous-cup solution samplers have been installed in a saltmarsh in west Cumbria, U.K. The sediments of this marsh are well known to contain elevated levels of transuranium elements (up to 16 000 Bq kg-1239,240 Pu) and it has been used for many years and by many workers as a site for the study of the geochemistry of the transuranium elements. Over a period of approximately 18 months, nine sets of porewater samples were collected. Sediment core samples were also collected from each zone of the marsh. The stable element compositions of the solution phase are generally as expected in an estuarine system, simply reflecting mixing of sea- and freshwaters. The 239,240Pu concentrations in the upper and middle zones of the marsh are low, usually between 2 and 20 mBq l-1, and with mean values of about 5 mBq l-1, whilst those from the seaward zone of the marsh are approximately a factor of 6 higher, probably reflecting a much greater addition of seawater. The Kd values for 239,240Pu in the sediments lie between 104 and 106, comparable to the values found by other workers near this site. Nevertheless, there are considerable fluctuations in Kd over time, and also substantial variations in Kd with depth in the sediment profile, and it may be that the assumption of chemical equilibrium underlying the use of Kd values is not valid in this system

Analysis of Motor Vehicle Sources and Their Contribution to Ambient Hydrocarbon Distributions at Urban Sites In Toronto During the Southern Ontario Oxidants Study

Hydrocarbon distributions measured in the urban area of Toronto during the Southern Ontario Oxidants Study of 1992 are presented. Comparison is made to hydrocarbon distributions measured in other urban areas. Relative concentrations of olefins were found to be depleted aloft compared to the surface level measurements. Chemical mass balance modelling was used to apportion the measured hydrocarbon distributions at York University and other roadside sites to gasoline based sources. The most dominant contributing source was vehicle exhaust. The relative amount of unburned gasoline at York University was found to be significant in the summer, and higher than that observed there during the winter or at other roadside sites. The relative amount of evaporative emissions (gasoline vapour) apportioned by the CMB model at roadside sites was compared to evaporative emissions predicted by a mobile emission factor model, MOBILE5C. The percentage of gasoline based non-methane hydrocarbons (NMHC) apportioned to gasoline vapour by the CMB model was equivalent within error to the relative amount of evaporative NMHC predicted by the MOBILE5C model for summer temperatures. For winter temperatures, the MOBILE5C model predicted significantly less evaporative emissions than that apportioned by the CMB model. An anthropogenic source of isoprene in the urban area has been proposed and tested. The inclusion of an isoprene flux in the exhaust source profile, consistent with that measured in the Auto/Oil Air Quality Improvement Research Program, results in calculated isoprene concentrations that are in agreement with observed concentrations at roadside sites and at York University in the winter. During summer, the combustion related isoprene can only account for a small fraction of the observed isoprene at downtown sites and at York University, at most 20%