Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta

Preventive chemotherapy has long been practiced against nematode parasites of livestock, leading to widespread drug resistance, and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance. Given that the genetic architecture of resistance is poorly understood for any nematode, we have analyzed multidrug resistant Teladorsagia circumcincta, a major parasite of sheep, as a model for analysis of resistance selection. We introgressed a field-derived multiresistant genotype into a partially inbred susceptible genetic background (through repeated backcrossing and drug selection) and performed genome-wide scans in the backcross progeny and drug-selected F2 populations to identify the major genes responsible for the multidrug resistance. We identified variation linking candidate resistance genes to each drug class. Putative mechanisms included target site polymorphism, changes in likely regulatory regions and copy number variation in efflux transporters. This work elucidates the genetic architecture of multiple anthelmintic resistance in a parasitic nematode for the first time and establishes a framework for future studies of anthelmintic resistance in nematode parasites of humans

Genome Sequence of Cronobacter sakazakii BAA-894 and Comparative Genomic Hybridization Analysis with Other Cronobacter Species

The genus Cronobacter (formerly called Enterobacter sakazakii) is composed of five species; C. sakazakii, C. malonaticus, C. turicensis, C. muytjensii, and C. dublinensis. The genus includes opportunistic human pathogens, and the first three species have been associated with neonatal infections. The most severe diseases are caused in neonates and include fatal necrotizing enterocolitis and meningitis. The genetic basis of the diversity within the genus is unknown, and few virulence traits have been identified.We report here the first sequence of a member of this genus, C. sakazakii strain BAA-894. The genome of Cronobacter sakazakii strain BAA-894 comprises a 4.4 Mb chromosome (57% GC content) and two plasmids; 31 kb (51% GC) and 131 kb (56% GC). The genome was used to construct a 387,000 probe oligonucleotide tiling DNA microarray covering the whole genome. Comparative genomic hybridization (CGH) was undertaken on five other C. sakazakii strains, and representatives of the four other Cronobacter species. Among 4,382 annotated genes inspected in this study, about 55% of genes were common to all C. sakazakii strains and 43% were common to all Cronobacter strains, with 10-17% absence of genes.CGH highlighted 15 clusters of genes in C. sakazakii BAA-894 that were divergent or absent in more than half of the tested strains; six of these are of probable prophage origin. Putative virulence factors were identified in these prophage and in other variable regions. A number of genes unique to Cronobacter species associated with neonatal infections (C. sakazakii, C. malonaticus and C. turicensis) were identified. These included a copper and silver resistance system known to be linked to invasion of the blood-brain barrier by neonatal meningitic strains of Escherichia coli. In addition, genes encoding for multidrug efflux pumps and adhesins were identified that were unique to C. sakazakii strains from outbreaks in neonatal intensive care units

Global assessment of the effect of climate change on ammonia emissions from seabirds

Seabird colonies alter the biogeochemistry of nearby ecosystems, while the associated emissions of ammonia (NH3) may cause acidification and eutrophication of finely balanced biomes. To examine the possible effects of future climate change on the magnitude and distribution of seabird NH3 emissions globally, a global seabird database was used as input to the GUANO model, a dynamic mass-flow process-based model that simulates NH3 losses from seabird colonies at an hourly resolution in relation to environmental conditions. Ammonia emissions calculated by the GUANO model were in close agreement with measured NH3 emissions across a wide range of climates. For the year 2010, the total global seabird NH3 emission is estimated at 82 [37–127] Gg year−1. This is less than previously estimated using a simple temperature-dependent empirical model, mainly due to inclusion of nitrogen wash-off from colonies during precipitation events in the GUANO model. High precipitation, especially between 40° and 60° S, results in total emissions for the penguin species that are 82% smaller than previously estimated, while for species found in dry tropical areas, emissions are 83–133% larger. Application of temperature anomalies for several IPCC scenarios for 2099 in the GUANO model indicated a predicted net increase in global seabird NH3 emissions of 27% (B1 scenario) and 39% (A2 scenario), compared with the 2010 estimates. At individual colonies, the net change was the result of influences of temperature, precipitation and relative humidity change, with smaller effects of wind-speed changes. The largest increases in NH3 emissions (mean: 60% [486 to −50] increase; A2 scenario for 2099 compared with 2010) were found for colonies 40°S to 65°N, and may lead to increased plant growth and decreased biodiversity by eliminating nitrogen sensitive plant species. Only 7% of the seabird colonies assessed globally (mainly limited to the sub-polar Southern Ocean) were estimated to experience a reduction in NH3 emission (average: −18% [-50 to 0] reduction between 2010 and 2099, A2 scenario), where an increase in precipitation was found to more than offset the effect of rising temperatures

The role of long-range transport and domestic emissions in determining atmospheric secondary inorganic particle concentrations across the UK

Surface concentrations of secondary inorganic particle components over the UK have been analysed for 2001–2010 using the EMEP4UK regional atmospheric chemistry transport model and evaluated against measurements. Gas/particle partitioning in the EMEP4UK model simulations used a bulk approach, which may lead to uncertainties in simulated secondary inorganic aerosol. However, model simulations were able to accurately represent both the long-term decadal surface concentrations of particle sulfate and nitrate and an episode in early 2003 of substantially elevated nitrate measured across the UK by the AGANet network. The latter was identified as consisting of three separate episodes, each of less than 1 month duration, in February, March and April. The primary cause of the elevated nitrate levels across the UK was meteorological: a persistent high-pressure system, whose varying location impacted the relative importance of transboundary versus domestic emissions. Whilst long-range transport dominated the elevated nitrate in February, in contrast it was domestic emissions that mainly contributed to the March episode, and for the April episode both domestic emissions and long-range transport contributed. A prolonged episode such as the one in early 2003 can have substantial impact on annual average concentrations. The episode led to annual concentration differences at the regional scale of similar magnitude to those driven by long-term changes in precursor emissions over the full decade investigated here. The results demonstrate that a substantial part of the UK, particularly the south and southeast, may be close to or exceeding annual mean limit values because of import of inorganic aerosol components from continental Europe under specific conditions. The results reinforce the importance of employing multiple year simulations in the assessment of emissions reduction scenarios on particulate matter concentrations and the need for international agreements to address the transboundary component of air pollution

Effects of sprint interval training on ectopic lipids and tissue-specific insulin sensitivity in men with non-alcoholic fatty liver disease

Purpose: This study examined the feasibility of sprint interval exercise training (SIT) for men with non-alcoholic fatty liver disease (NAFLD) and its effects on intrahepatic triglyceride (IHTG), insulin sensitivity (hepatic and peripheral), visceral (VAT) and subcutaneous adipose tissue (ScAT). Methods: Nine men with NAFLD (age 41 ± 8 years; BMI 31.7 ± 3.1 kg m−2; IHTG 15.6 ± 8.3%) were assessed at: (1) baseline (2) after a control phase of no intervention (pre-training) and (3) after 6 weeks of SIT (4–6 maximal 30 s cycling intervals, three times per week). IHTG, VAT and ScAT were measured using magnetic resonance spectroscopy or imaging and insulin sensitivity was assessed via dual-step hyperinsulinaemic-euglycaemic clamp with [6,6-D2] glucose tracer. Results: Participants adhered to SIT, completing ≥ 96.7% of prescribed intervals. SIT increased peak oxygen uptake [ V O2peak: + 13.6% (95% CI 8.8–18.2%)] and elicited a relative reduction in IHTG [− 12.4% (− 31.6 to 6.7%)] and VAT [− 16.9% (− 24.4 to − 9.4%); n = 8], with no change in body weight or ScAT. Peripheral insulin sensitivity increased throughout the study (n = 8; significant main effect of phase) but changes from pre- to post-training were highly variable (range − 18.5 to + 58.7%) and not significant (P = 0.09), despite a moderate effect size (g* = 0.63). Hepatic insulin sensitivity was not influenced by SIT. Conclusions: SIT is feasible for men with NAFLD in a controlled laboratory setting and is able to reduce IHTG and VAT in the absence of weight loss

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Emissions and Removals of Greenhouse Gases from Land Use, Land Use Change and Forestry (LULUCF) for England, Scotland, Wales and Northern Ireland: 1990-2009

This report presents a summary of the net emissions and removals of greenhouse gases for 1990-2010 by the Land Use, Land Use Change and Forestry sector for each of the Devolved Administrations (England, Scotland, Wales and Northern Ireland). Supporting data is available at http://naei.defra.gov.uk/report_link.php?report_id=692. A full report for the UK is available in the 1990-2010 UK Greenhouse Gas Inventory Report, available on the National Atmospheric Emissions Inventory website http://naei.defra.gov.uk/. The LULUCF sector in England was a net source of GHG emissions in 2010 (1.642 Mt CO2e). The size of this source has diminished since 1990. The LULUCF sector in Scotland was a net sink of GHG emissions in 2010 (-5.459 Mt CO2e). This sink increased steadily from 1990 to 2009 but shrank slightly in 2010. The LULUCF sector in Wales was a small net sink of GHG emissions in 2010 (-0.042 Mt CO2e). Net emissions/removals have fluctuated between source and sink since 1990. The LULUCF sector in Northern Ireland was a small net source in 2010 (0.105 Mt CO2e) but was a small sink between 1990 and 2005. Small changes between this and the 1990-2009 inventory are due to the inclusion of new activity data and some minor revisions in methods

Legislation and SME retailers – compliance costs and consequences

Purpose – The introduction, implementation and enforcement of new laws governing the conduct of business can result in substantial additional costs to retailers. Focusing on small to medium sized (SME) retailers in rural areas and market towns, the study reported here aims to provide an understanding of perceptions of potentially disproportionate implementation costs and the resulting consequences. Design/methodology/approach – A three-stage design was used. An exploratory focus group with representatives of the Rural Shop Alliance was followed by seven semi-structured depth-interviews with SME retail representatives. Thematic analysis of the qualitative findings formed the basis for a survey of SME retailers in five market towns. Findings – Findings show SME retailers' perceptions of the differential burden related to the impact of new legislation, with the key factors of direct cost, time costs and information costs. Consequently, business growth and the formalisation of staffing arrangements, in particular, can be obstructed. Generally, good relationships with Trading Standards and Environmental Health Officers are often driven by a need for reactive compliance rather than offering a proactive information and support mechanism. Practical implications – Findings clarify the nature of the differential burden of legislation to retail SMEs. The need for an “outcomes-for-business” driven proactive stance by local delivery agencies is highlighted. Ongoing support visits, telephone help lines and leaflets and the press rather than the internet are identified as key information sources. Originality/value – Both qualitative and quantitative evidence is brought together in the assessment of an area of concern to retail SMEs