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Genome-wide association (GWA) studies have thus far identified 10 loci at which common variants influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci, we conducted a meta-analysis of three GWA studies from the UK totalling 3,334 cases and 4,628 controls, followed by multiple validation analyses, involving a total of 18,095 CRC cases and 20,197 controls. We identified new associations at 4 CRC risk loci: 1q41 (rs6691170, OR=1.06, P=9.55x10-10; rs6687758, OR=1.09, P=2.27x10-9); 3q26.2 (rs10936599, OR=0.93, P=3.39x10-8); 12q13.13 (rs11169552, OR=0.92, P=1.89x10-10; rs7136702, OR=1.06, P=4.02=x10-8); and 20q13.33 (rs4925386, OR=0.93, P=1.89x10-10). As well as identifying multiple new CRC risk loci this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.

Size-fractionated samples of airborne particulate matter have been collected in a number of campaigns at Marylebone Road, London and simultaneously at background sites either in Regents Park or at North Kensington. Analysis of these samples has enabled size distributions of total mass and of a number of elements to be determined, and roadside increments attributable to nonexhaust emissions arising from traffic activity have been calculated. Taking a novel approach, the combined use of size distribution information and tracer elements has allowed the separate estimation of the contributions of brake dust, tire dust, and resuspension to particle mass in the range 0.9-11.5 μm aerodynamic diameter and mean contributions (± s.e.) at the Marylebone Road sampling site are estimated as resuspended dust 38.1 ± 9.7%, brake dust 55.3 ± 7.0%, and tire dust 10.7 ± 2.3%, (accounting for a total of 104.1% of coarse particle mass in the traffic increment above background).

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Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10−10) and BMP2 (rs4813802, P = 4.65×10−11). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10−8) and rs11632715 (P = 2.30×10−10). As low-penetrance predisposition variants become harder to identify—owing to small effect sizes and/or low risk allele frequencies—approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.

Extracellular adenosine-5′-triphosphate (ATP) induces a number of cellular responses in plants and animals. Some of the molecular components for purinergic signaling in animal cells appear to be lacking in plant cells, although some cellular responses are similar in both systems [e.g. increased levels of cytosolic free calcium, nitric oxide (NO), and reactive oxygen species (ROS)]. The purpose of this review is to compare and contrast purinergic signaling mechanisms in animal and plant cells. This comparison will aid our overall understanding of plant physiology and also provide details of the general fundamentals of extracellular ATP signaling in eukaryotes.

The Clean Air for London (ClearfLo) project provides integrated measurements of the meteorology, composition, and particulate loading of the urban atmosphere in London, United Kingdom, to improve predictive capability for air quality. METEOROLOGY, AIR QUALITY, AND HEALTH IN LONDONThe ClearfLo Project Economic and Social Affairs 2013). Urban populations are exposed to stressful environmental conditions, such as local and nonlocal pollutants, that cause poor air quality and microclimates that exacerbate heat stress during heat waves. These are projected to increase in a warming climate. Our cities are therefore nexus points for several environmental health stresses that we currently face (Rydin et al. 2012) and the interacting issues around sustainability and human health.The purpose of this paper is to introduce the Clean Air for London (ClearfLo) project, which investigates the atmospheric science that underpins these health stresses, with a particular focus on the urban increment in atmospheric drivers. We focused on three atmospheric drivers of environmental health stress in cities, namely, heat, gas-phase pollutants, and particulate matter (PM). Health stresses from the urban atmospheric environment.Heat waves have an impact on human health. Populations typically display an optimal temperature range at which the (daily or weekly) mortality rate is lowest. Mortality rates rise as temperatures exceed this optimal range (e.g., Rydin et al. 2012). The 2003 European heat wave (Stedman 2004) in combination with air pollution was responsible for more than 2000 excess deaths in the United Kingdom (Johnson et al. 2005). Under a warming climate, the risks posed by heat stress are predicted to increase (Hacker et al. 2005). People living in urban environments are exposed to higher temperatures than in nonurban regions. Thus, heat-related deaths could be higher within urban areas (Mavrogianni et al. 2011). Hence, ClearfLo is concerned with measuring the factors controlling the urban atmospheric boundary layer, that is, the surface energy balance.The World Health Organization (WHO) reported (WHO 2006) that the strongest effects of air quality 779MAY 2015 AMERICAN METEOROLOGICAL SOCIETY | on health are attributable to PM, followed by ozone (O 3 ) and nitrogen dioxide (NO 2 ). A recent report (Guerreiro et al. 2013) indicates that in 2011 up to 88% of the urban population in Europe was exposed to concentrations exceeding the WHO air quality guidelines for PM 10 (defined as particles that pass through a size-selective inlet with a 50% efficiency cutoff at 10-µm aerodynamic diameter, representative of the inhalable fraction). It is estimated that a reduction of PM 10 to the WHO annual-mean guideline of 20 µg m −3 would reduce attributable deaths per year in Europe by 22,000. Further, this would lead to a substantial improvement in the quality of life for millions with a preexisting respiratory or cardiovascular disease (COMEAP 2010).Epidemiological studies consistently demonstrate an association between the PM mass concentr...

Total (as opposed to culturable) bacterial number counts are reported for four sites in the United Kingdom measured during campaigns over four separate seasons. These are interpreted in relation to simple climatic factors, i.e. temperature, wind speed and wind direction. Temperature has a marked effect at all four sites with data for a rural coastal site conforming best to a simple exponential model. Data for the other rural and urban locations show a baseline similar to that determined at the coastal rural location, but with some very significant positive excursions. The temperature dependence of bacterial number is found to conform to that typical of bacterial growth rates. At the coastal rural location, bacterial numbers normalised for temperature show no dependence on wind speed whilst at the inland sites there is a decrease with increasing wind speed of the form expected for a large area source. Only one site appeared to show a systematic relationship of bacterial concentrations to wind direction that being a site in the suburbs of Birmingham with highest number concentrations observed on a wind sector approaching from the city centre. PCR techniques have been used to identify predominant types of bacteria and results are presented which show that Bacillus was the dominant genus observed at the three inland sites during the winter and summer seasons. Pseudomonas appeared with comparable frequency at certain sites and seasons. There was in general a greater diversity of bacteria at the coastal site than at the inland sites.