A new method for estimating the adult survival rate of the Corncrake Crex crex and comparison with estimates from ring-recovery and ring-recapture data

The mean annual survival rate of adult Corncrakes Crex crex was estimated by three independent approaches: ring-recovery, ring-recapture and the shape of secondary remiges. The last method is new and uses measurements of the shape of the tips of the secondaries, which changes in the first post-juvenile wing moult to become less pointed. The estimates obtained by the three approaches were mutually compatible and indicated that annual survival is likely to be within the range 0.2–0.3. This low survival rate is likely to make the growth rate of Corncrake populations particularly sensitive to the effects of agricultural and conservation management on breeding success and recruitment. The survival rate of adult female Corncrakes was estimated for the first time (0.259) and was found not to differ significantly from an estimate for adult males (0.298) made in the same study area by the same method. It is concluded that the method based upon population counts and measurements of the shape of remiges has potential value for studies of the demography of Corncrakes and other species.     

Robustness despite uncertainty: regional climate data reveal the dominant role of humans in explaining global extinctions of Late Quaternary megafauna

Debate over the Late Quaternary megafaunal extinctions has focussed on whether human colonisation or climatic changes were more important drivers of extinction, with few extinctions being unambiguously attributable to either. Most analyses have been geographically or taxonomically restricted and the few quantitative global analyses have been limited by coarse temporal resolution or overly simplified climate reconstructions or proxies. We present a global analysis of the causes of these extinctions which uses high‐resolution climate reconstructions and explicitly investigates the sensitivity of our results to uncertainty in the palaeological record. Our results show that human colonisation was the dominant driver of megafaunal extinction across the world but that climatic factors were also important. We identify the geographic regions where future research is likely to have the most impact, with our models reliably predicting extinctions across most of the world, with the notable exception of mainland Asia where we fail to explain the apparently low rate of extinction found in in the fossil record. Our results are highly robust to uncertainties in the palaeological record, and our main conclusions are unlikely to change qualitatively following minor improvements or changes in the dates of extinctions and human colonisation.     

The discovery of long acting beta2-adrenoreceptor agonists

The design and profile of a series of saligenin containing long acting beta(2)-adrenoreceptor agonists is described. Evaluation of these analogues using a guinea-pig tissue model demonstrates that analogues within this series have significantly longer durations of action than salmeterol and have the potential for a once daily profile in human.     

Potential Hazard to Human Health from Exposure to Fragments of Lead Bullets and Shot in the Tissues of Game Animals

Background

Lead is highly toxic to animals. Humans eating game killed using lead ammunition generally avoid swallowing shot or bullets and dietary lead exposure from this source has been considered low. Recent evidence illustrates that lead bullets fragment on impact, leaving small lead particles widely distributed in game tissues. Our paper asks whether lead gunshot pellets also fragment upon impact, and whether lead derived from spent gunshot and bullets in the tissues of game animals could pose a threat to human health.

Methodology/Principal Findings

Wild-shot gamebirds (6 species) obtained in the UK were X-rayed to determine the number of shot and shot fragments present, and cooked using typical methods. Shot were then removed to simulate realistic practice before consumption, and lead concentrations determined. Data from the Veterinary Medicines Directorate Statutory Surveillance Programme documenting lead levels in raw tissues of wild gamebirds and deer, without shot being removed, are also presented. Gamebirds containing ≥5 shot had high tissue lead concentrations, but some with fewer or no shot also had high lead concentrations, confirming X-ray results indicating that small lead fragments remain in the flesh of birds even when the shot exits the body. A high proportion of samples from both surveys had lead concentrations exceeding the European Union Maximum Level of 100 ppb w.w. (0.1 mg kg⁻¹ w.w.) for meat from bovine animals, sheep, pigs and poultry (no level is set for game meat), some by several orders of magnitude. High, but feasible, levels of consumption of some species could result in the current FAO/WHO Provisional Weekly Tolerable Intake of lead being exceeded.

Conclusions/Significance

The potential health hazard from lead ingested in the meat of game animals may be larger than previous risk assessments indicated, especially for vulnerable groups, such as children, and those consuming large amounts of game.     

De novo assembly of the Pseudomonas syringae pv. syringae B728a genome using Illumina/Solexa short sequence reads

Illumina's Genome Analyzer generates ultra-short sequence reads, typically 36 nucleotides in length, and is primarily intended for resequencing. We tested the potential of this technology for de novo sequence assembly on the 6 Mbp genome of Pseudomonas syringae pv. syringae B728a with several freely available assembly software packages. Using an unpaired data set, velvet assembled >96% of the genome into contigs with an N50 length of 8289 nucleotides and an error rate of 0.33%. edena generated smaller contigs (N50 was 4192 nucleotides) and comparable error rates. ssake and vcake yielded shorter contigs with very high error rates. Assembly of paired-end sequence data carrying 400 bp inserts produced longer contigs (N50 up to 15 628 nucleotides), but with increased error rates (0.5%). Contig length and error rate were very sensitive to the choice of parameter values. Noncoding RNA genes were poorly resolved in de novo assemblies, while >90% of the protein-coding genes were assembled with 100% accuracy over their full length. This study demonstrates that, in practice, de novo assembly of 36-nucleotide reads can generate reasonably accurate assemblies from about 40 × deep sequence data sets. These draft assemblies are useful for exploring an organism's proteomic potential, at a very economic low cost.     

Development of a Brief Measure to Assess Quality of Life in Obesity

Objective: Obesity researchers have a growing interest in measuring the impact of weight and weight reduction on quality of life. The Impact of Weight on Quality of Life questionnaire (IWQOL) was the first self‐report instrument specifically developed to assess the effect of obesity on quality of life. Although the IWQOL has demonstrated excellent psychometric properties, its length (74 items) makes it somewhat cumbersome as an outcome measure in clinical research. This report describes the development of a 31‐item version of the IWQOL (IWQOL‐Lite). Research Methods and Procedures: IWQOLs from 996 obese patients and controls were used to develop the IWQOL‐Lite. Psychometric properties of the IWQOL‐Lite were examined in a separate cross‐validation sample of 991 patients and controls. Results: Confirmatory factor analysis provided strong support for the adequacy of the scale structure. The five identified scales of the IWQOL‐Lite (Physical Function, Self‐Esteem, Sexual Life, Public Distress, and Work) and the total IWQOL‐Lite score demonstrated excellent psychometric properties. The reliability of the IWQOL‐Lite scales ranged from 0.90 to 0.94 and was 0.96 for the total score. Correlations between the IWQOL‐Lite and collateral measures supported the construct validity of the IWQOL‐Lite. Changes in IWQOL‐Lite scales over time correlated significantly with changes in weight, supporting its sensitivity to change. Significant differences in IWQOL‐Lite scale and total scores were found among groups differing in body mass index, supporting the utility of the IWQOL‐Lite across the body mass index spectrum. Discussion: The IWQOL‐Lite appears to be a psychometrically sound and clinically sensitive brief measure of quality of life in obese persons.     

Economic analysis of a modified dry grind ethanol process with recycle of pretreated and enzymatically hydrolyzed distillers' grains

A modification of the conventional dry grind process for producing ethanol from yellow dent corn is considered with respect to its economic value. Process modifications include recycling distillers' grains, after being pretreated and hydrolyzed, with the ground corn and water to go through fermentation again and increase ethanol yields from the corn starch. A dry grind financial model, which has been validated against other financial models in the industry, is utilized to determine the financial impact of the process changes. The hypothesis was that the enhanced process would yield higher revenues through additional ethanol sales, and higher valued dried distillers' grains (DDGS), due to its higher protein content, to mitigate the drop in DDGS yields. A 32% increase in net present value (NPV) for the overall operation is expected when applying the process modifications to a 100million gallon ethanol plant, and an enzyme cost of $0.20 for each additional gallon of ethanol produced. However, there may be no value added to the enhanced dried distillers' grains (eDDGS), even in light of its higher protein levels, as current pricing is expected to be more sensitive to the amino acid profile than the total protein level, and the eDDGS has lower lysine levels, a key amino acid. Thus, there is a decrease in revenue from eDDGS due to the combination of no price change and loss of DDGS yield to ethanol. The financial improvements are a result of the increased revenue from higher ethanol yields outpacing the sum of all added costs, which include higher capital costs, larger loan payments, increased operating costs, and decreased revenues from dried distillers' grains.     

Stress-response balance drives the evolution of a network module and its host genome

Stress response genes and their regulators form networks that underlie drug resistance. These networks often have an inherent tradeoff: their expression is costly in the absence of stress, but beneficial in stress. They can quickly emerge in the genomes of infectious microbes and cancer cells, protecting them from treatment. Yet, the evolution of stress resistance networks is not well understood. Here, we use a two-component synthetic gene circuit integrated into the budding yeast genome to model experimentally the adaptation of a stress response module and its host genome in three different scenarios. In agreement with computational predictions, we find that: (i) intra-module mutations target and eliminate the module if it confers only cost without any benefit to the cell; (ii) intra- and extra-module mutations jointly activate the module if it is potentially beneficial and confers no cost; and (iii) a few specific mutations repeatedly fine-tune the module''s noisy response if it has excessive costs and/or insufficient benefits. Overall, these findings reveal how the timing and mechanisms of stress response network evolution depend on the environment.     

pfmdr1 mutations associated with chloroquine resistance incur a fitness cost in Plasmodium falciparum

Efforts to control malaria worldwide have been hindered by the development and expansion of parasite populations resistant to many first-line antimalarial compounds. Two of the best-characterized determinants of drug resistance in the human malaria parasite Plasmodium falciparum are pfmdr1 and pfcrt, although the mechanisms by which resistance is mediated by these genes is still not clear. In order to determine whether mutations in pfmdr1 associated with chloroquine resistance affect the capacity of the parasite to persist when drug pressure is removed, we conducted competition experiments between P. falciparum strains in which the endogenous pfmdr1 locus was modified by allelic exchange. In the absence of selective pressure, the component of chloroquine resistance attributable to mutations at codons 1034, 1042 and 1246 in the pfmdr1 gene also gave rise to a substantial fitness cost in the intraerythrocytic asexual stage of the parasite. The loss of fitness incurred by these mutations was calculated to be 25% with respect to an otherwise genetically identical strain in which wild-type polymorphisms had been substituted at these three codons. At least part of the fitness loss may be attributed to a diminished merozoite viability. These in vitro results support recent in vivo observations that in several countries where chloroquine use has been suspended because of widespread resistance, sensitive strains are re-emerging.     

Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis

Myosin VI plays a role in the maintenance of Golgi morphology and in exocytosis. In a yeast 2-hybrid screen we identified optineurin as a binding partner for myosin VI at the Golgi complex and confirmed this interaction in a range of protein interaction studies. Both proteins colocalize at the Golgi complex and in vesicles at the plasma membrane. When optineurin is depleted from cells using RNA interference, myosin VI is lost from the Golgi complex, the Golgi is fragmented and exocytosis of vesicular stomatitis virus G-protein to the plasma membrane is dramatically reduced. Two further binding partners for optineurin have been identified: huntingtin and Rab8. We show that myosin VI and Rab8 colocalize around the Golgi complex and in vesicles at the plasma membrane and overexpression of constitutively active Rab8-Q67L recruits myosin VI onto Rab8-positive structures. These results show that optineurin links myosin VI to the Golgi complex and plays a central role in Golgi ribbon formation and exocytosis.