Tropospheric reactive odd nitrogen over the South Pacific in austral springtime

The distribution of reactive nitrogen species over the South Pacific during austral springtime appears to be dominated by biomass burning emissions and possibly lightning and stratospheric inputs. The absence of robust correlations of reactive nitrogen species with source-specific tracers (e.g., C2H2 [combustion], CH3Cl [biomass burning], C2Cl4 [industrial],210Pb [continental], and 7Be [stratospheric]) suggests significant aging and processing of the sampled air parcels due to losses by surface deposition, OH attack, and dilution processes. Classification of the air parcels based on CO enhancements indicates that the greatest influence was found in plumes at 3–8 km altitude in the distributions of HNO3 and peroxyacetyl nitrate (PAN). Here mixing ratios of these species reached 600 parts per trillion by volume (pptv), values surprisingly large for a location several thousand kilometers removed from the nearest continental areas. The mixing ratio of total reactive nitrogen (the NOy sum), operationally defined in this paper as measured (NO + HNO3 + PAN + CH3ONO2 + C2H5ONO2) + modeled (NO2), had a median value of 285 pptv within these plumes compared with 120 pptv in nonplume air parcels. Particle NO−3 was not included in this analysis of the NOy sum due to its 10- to 15-min sampling time resolution, but, in general, it was \u3c10% of the NOy sum. Comparison of the two air parcel classifications for NOy and alkyl nitrate distributions showed no perceivable plume influence, but recycling of reactive nitrogen may have masked this direct effect. In the marine boundary layer, the NOy sum averaged 50 pptv in both air parcel classifications, being somewhat isolated from the polluted conditions above it by the trade wind inversion. In this region, however, alkyl nitrates appear to have an important marine source where they comprise 20–80% of the NOy sum in equatorial and high-latitude regions over the South Pacific

The feasibility of using pedometers and brief advice to increase activity in sedentary older women:a pilot study

Background: People over the age of 70 carry the greatest burden of chronic disease, disability and health care use. Participation in physical activity is crucial for health, and walking accounts for much of the physical activity undertaken by sedentary individuals. Pedometers are a useful motivational tool to encourage increased walking and they are cheap and easy to use. The aim of this pilot study was to evaluate the feasibility of the use of pedometers plus a theory-based intervention to assist sedentary older women to accumulate increasing amounts of physical activity, mainly through walking. Methods: Female participants over the age of 70 were recruited from primary care and randomised to receive either pedometer plus a theory-based intervention or a theory-based intervention alone. The theory-based intervention consisted of motivational techniques, goal-setting, barrier identification and self-monitoring with pedometers and daily diaries. The pedometer group were further randomised to one of three target groups: a 10%, 15% or 20% monthly increase in step count to assess the achievability and acceptability of a range of targets. The primary outcome was change in daily activity levels measured by accelerometry. Secondary outcome measures were lower limb function, health related quality of life, anxiety and depression. Results: 54 participants were recruited into the study, with an average age of 76. There were 9 drop outs, 45 completing the study. All participants in the pedometer group found the pedometers easy to use and there was good compliance with diary keeping (96% in the pedometer group and 83% in the theory-based intervention alone group). There was a strong correlation (0.78) between accelerometry and pedometer step counts i.e. indicating that walking was the main physical activity amongst participants. There was a greater increase in activity (accelerometry) amongst those in the 20% target pedometer group compared to the other groups, although not reaching statistical significance (p = 0.192). Conclusion: We have demonstrated that it is feasible to use pedometers and provide theory-based advice to community dwelling sedentary older women to increase physical activity levels and a larger study is planned to investigate this further.Publisher PDFPeer reviewe

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Comparative Genome Analysis Reveals an Absence of Leucine-Rich Repeat Pattern-Recognition Receptor Proteins in the Kingdom Fungi

Background: In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack. Methodology/Principal Findings: A survey of genome sequences from 101 species, representing a broad cross-section of the eukaryotic phylogenetic tree, reveals an absence of leucine rich repeat-domain containing receptors in the fungal kingdom. Uniquely, however, fungi possess adenylate cyclases that contain distinct leucine rich repeat-domains, which have been demonstrated to act as an alternative means of perceiving the presence of bacteria by at least one fungal species. Interestingly, the morphologically similar osmotrophic oomycetes, which are taxonomically distant members of the stramenopiles, possess pattern recognition receptors with similar domain structures to those found in plants. Conclusions: The absence of pattern recognition receptors suggests that fungi may possess novel classes of patternrecognition receptor, such as the modified adenylate cyclase, or instead rely on secretion of anti-microbial secondary metabolites for protection from microbial attack. The absence of pattern recognition receptors in fungi, coupled with their abundance in oomycetes, suggests this may be a unique characteristic of the fungal kingdom rather than a consequence o

Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations

Anti-Apoptotic Machinery Protects the Necrotrophic Fungus Botrytis cinerea from Host-Induced Apoptotic-Like Cell Death during Plant Infection

Necrotrophic fungi are unable to occupy living plant cells. How such pathogens survive first contact with living host tissue and initiate infection is therefore unclear. Here, we show that the necrotrophic grey mold fungus Botrytis cinerea undergoes massive apoptotic-like programmed cell death (PCD) following germination on the host plant. Manipulation of an anti-apoptotic gene BcBIR1 modified fungal response to PCD-inducing conditions. As a consequence, strains with reduced sensitivity to PCD were hyper virulent, while strains in which PCD was over-stimulated showed reduced pathogenicity. Similarly, reduced levels of PCD in the fungus were recorded following infection of Arabidopsis mutants that show enhanced susceptibility to B. cinerea. When considered together, these results suggest that Botrytis PCD machinery is targeted by plant defense molecules, and that the fungal anti-apoptotic machinery is essential for overcoming this host-induced PCD and hence, for establishment of infection. As such, fungal PCD machinery represents a novel target for fungicides and antifungal drugs