A chromosome scale assembly of the parasitoid wasp Venturia canescens provides insight into the process of virus domestication.

The parasitoid wasp Venturia canescens is an important biological control agent of stored products moth pests and serves as a model to study the function and evolution of domesticated endogenous viruses (DEVs). The DEVs discovered in V. canescens are known as virus-like particles (VcVLPs), which are produced using nudivirus-derived components and incorporate wasp-derived virulence proteins instead of packaged nucleic acids. Previous studies of virus-derived components in the V. canescens genome identified 53 nudivirus-like genes organized in six gene clusters and several viral pseudogenes, but how VcVLP genes are organized among wasp chromosomes following their integration in the ancestral wasp genome is largely unknown. Here, we present a chromosomal scale genome of V. canescens consisting of 11 chromosomes and 56 unplaced small scaffolds. The genome size is 290.8 Mbp with a N50 scaffold size of 24.99 Mbp. A high-quality gene set including 11,831 protein-coding genes were produced using RNA-Seq data as well as publicly available peptide sequences from related Hymenoptera. A manual annotation of genes of viral origin produced 61 intact and 19 pseudogenized nudivirus-derived genes. The genome assembly revealed that two previously identified clusters were joined into a single cluster and a total of 5 gene clusters comprising of 60 intact nudivirus-derived genes were located in three chromosomes. In contrast, pseudogenes are dispersed among 8 chromosomes with only 4 pseudogenes associated with nudivirus gene clusters. The architecture of genes encoding VcVLP components suggests it originates from a recent virus acquisition and there is a link between the processes of dispersal and pseudogenization. This high-quality genome assembly and annotation represents the first chromosome-scale assembly for parasitoid wasps associated with VLPs, and is publicly available in the National Center for Biotechnology Information Genome and RefSeq databases, providing a valuable resource for future studies of DEVs in parasitoid wasps.

Determining the best population-level alcohol consumption model and its impact on estimates of alcohol-attributable harms.

BACKGROUND: The goals of our study are to determine the most appropriate model for alcohol consumption as an exposure for burden of disease, to analyze the effect of the chosen alcohol consumption distribution on the estimation of the alcohol Population- Attributable Fractions (PAFs), and to characterize the chosen alcohol consumption distribution by exploring if there is a global relationship within the distribution. METHODS: To identify the best model, the Log-Normal, Gamma, and Weibull prevalence distributions were examined using data from 41 surveys from Gender, Alcohol and Culture: An International Study (GENACIS) and from the European Comparative Alcohol Study. To assess the effect of these distributions on the estimated alcohol PAFs, we calculated the alcohol PAF for diabetes, breast cancer, and pancreatitis using the three above-named distributions and using the more traditional approach based on categories. The relationship between the mean and the standard deviation from the Gamma distribution was estimated using data from 851 datasets for 66 countries from GENACIS and from the STEPwise approach to Surveillance from the World Health Organization. RESULTS: The Log-Normal distribution provided a poor fit for the survey data, with Gamma and Weibull distributions providing better fits. Additionally, our analyses showed that there were no marked differences for the alcohol PAF estimates based on the Gamma or Weibull distributions compared to PAFs based on categorical alcohol consumption estimates. The standard deviation of the alcohol distribution was highly dependent on the mean, with a unit increase in alcohol consumption associated with a unit increase in the mean of 1.258 (95% CI: 1.223 to 1.293) (R2 = 0.9207) for women and 1.171 (95% CI: 1.144 to 1.197) (R2 = 0. 9474) for men. CONCLUSIONS: Although the Gamma distribution and the Weibull distribution provided similar results, the Gamma distribution is recommended to model alcohol consumption from population surveys due to its fit, flexibility, and the ease with which it can be modified. The results showed that a large degree of variance of the standard deviation of the alcohol consumption Gamma distribution was explained by the mean alcohol consumption, allowing for alcohol consumption to be modeled through a Gamma distribution using only average consumption.

Mortality and potential years of life lost attributable to alcohol consumption in Canada in 2005.

BACKGROUND: Alcohol is a substantial risk factor for mortality according to the recent 2010 World Health Assembly strategy to reduce the harmful use of alcohol which outlined the need to characterize and monitor this burden. Accordingly, using new methodology we estimated 1) the number of deaths caused and prevented by alcohol consumption, and 2) the potential years of life lost (PYLLs) attributable to alcohol consumption in Canada in 2005. METHODS: Mortality attributable to alcohol consumption was estimated by calculating Alcohol-Attributable Fractions (AAFs) (defined as the proportion of mortality that would be eliminated if the exposure was eliminated) using data from various sources. Indicators for alcohol consumption were obtained from the Canadian Alcohol and Drug Use Monitoring Survey 2008 and corrected for adult per capita recorded and unrecorded alcohol consumption. Risk relations were taken from the Comparative Risk Assessment within the current Global Burden of Disease (GBD) study. Due to concerns about the reliability of information specifying causes of death for people aged 65 or older, our analysis was limited to individuals aged 0 to 64 years. Calculation of the 95% confidence intervals (CIs) for the AAFs was performed using Monte Carlo random sampling. Information on mortality was obtained from Statistics Canada. A sensitivity analysis was performed comparing the mortality results obtained using our study methods to results obtained using previous methodologies. RESULTS: In 2005, 3,970 (95% CI: 810 to 7,170) deaths (4,390 caused and 420 prevented) and 134,555 (95% CI: 36,690 to 236,376) PYLLs were attributable to alcohol consumption for individuals aged 0 to 64 years. These figures represent 7.7% (95% CI: 1.6% to 13.9%) of all deaths and 8.0% (95% CI: 2.2% to 14.1%) of all PYLLs for individuals aged 0 to 64 years. The sensitivity analysis showed that the number of deaths as measured by this new methodology is greater than that if mortality was estimated using previous methodologies. CONCLUSIONS: The mortality burden attributable to alcohol consumption for Canada is large, unnecessary, and could be substantially reduced in a short period of time if effective public health policies were implemented. A monitoring system on alcohol consumption is imperative and would greatly assist in planning and evaluating future Canadian public health policies related to alcohol consumption.

Estimating uncertainty of alcohol-attributable fractions for infectious and chronic diseases.

BACKGROUND: Alcohol is a major risk factor for burden of disease and injuries globally. This paper presents a systematic method to compute the 95% confidence intervals of alcohol-attributable fractions (AAFs) with exposure and risk relations stemming from different sources. METHODS: The computation was based on previous work done on modelling drinking prevalence using the gamma distribution and the inherent properties of this distribution. The Monte Carlo approach was applied to derive the variance for each AAF by generating random sets of all the parameters. A large number of random samples were thus created for each AAF to estimate variances. The derivation of the distributions of the different parameters is presented as well as sensitivity analyses which give an estimation of the number of samples required to determine the variance with predetermined precision, and to determine which parameter had the most impact on the variance of the AAFs. RESULTS: The analysis of the five Asian regions showed that 150 000 samples gave a sufficiently accurate estimation of the 95% confidence intervals for each disease. The relative risk functions accounted for most of the variance in the majority of cases. CONCLUSIONS: Within reasonable computation time, the method yielded very accurate values for variances of AAFs.

Statistical modeling of volume of alcohol exposure for epidemiological studies of population health: the US example.

BACKGROUND: Alcohol consumption is a major risk factor in the global burden of disease, with overall volume of exposure as the principal underlying dimension. Two main sources of data on volume of alcohol exposure are available: surveys and per capita consumption derived from routine statistics such as taxation. As both sources have significant problems, this paper presents an approach that triangulates information from both sources into disaggregated estimates in line with the overall level of per capita consumption. METHODS: A modeling approach was applied to the US using data from a large and representative survey, the National Epidemiologic Survey on Alcohol and Related Conditions. Different distributions (log-normal, gamma, Weibull) were used to model consumption among drinkers in subgroups defined by sex, age, and ethnicity. The gamma distribution was used to shift the fitted distributions in line with the overall volume as derived from per capita estimates. Implications for alcohol-attributable fractions were presented, using liver cirrhosis as an example. RESULTS: The triangulation of survey data with aggregated per capita consumption data proved feasible and allowed for modeling of alcohol exposure disaggregated by sex, age, and ethnicity. These models can be used in combination with risk relations for burden of disease calculations. Sensitivity analyses showed that the gamma distribution chosen yielded very similar results in terms of fit and alcohol-attributable mortality as the other tested distributions. CONCLUSIONS: Modeling alcohol consumption via the gamma distribution was feasible. To further refine this approach, research should focus on the main assumptions underlying the approach to explore differences between volume estimates derived from surveys and per capita consumption figures.

Alcohol-attributable burden of disease and injury in Canada, 2004.

OBJECTIVE: This analysis aimed to estimate the burden of disease and injury caused and prevented by alcohol in 2004 for Canadians aged 0-69 years and compare the effects of different magnitudes of adjustment of survey data on these estimates. METHODS: Alcohol indicators were obtained from the Canadian Alcohol and Drug Use Monitoring Survey 2008 and were corrected to 80% coverage using adult per capita recorded and unrecorded consumption. Risk relations were taken from meta-analyses. Estimates of burden of disease and injury were obtained from the World Health Organization. RESULTS: In 2004, 4,721 (95% CI 1,432-8,150) deaths and 274,663 (95% CI 201,397-352,432) disability-adjusted life years lost (DALYs) of Canadians 0-69 years of age were attributable to alcohol. This represented 7.1% (95% CI 2.1-12.2%) of all deaths and 9.3% (95% CI 6.8-11.9%) of DALYs for this age range. The sensitivity analysis showed that the outcome estimates varied substantially based on the adjusted coverage rate. CONCLUSION: More attention to burden of disease and injury statistics is required to accurately characterize alcohol-related harms. This burden is preventable and could be reduced by implementation of more effective policies.

Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study.

OBJECTIVE: To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. DESIGN: Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. PARTICIPANTS: 109,118 men and 254,870 women, mainly aged 37-70. MAIN OUTCOME MEASURES: Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. RESULTS: If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (-3 to 38%) for liver, 17% (10 to 25%) and 4% (-1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33,037 of 178,578 alcohol related cancer cases in men and 17,470 of 397,043 alcohol related cases in women. CONCLUSIONS: In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

The relation between different dimensions of alcohol consumption and burden of disease: an overview.

AIMS: As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. METHODS: Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. RESULTS: Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose-response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. CONCLUSIONS: Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol-disease relationships.

First principle computational study on the full conformational space of L-proline diamides.

Ab initio molecular orbital computations were carried out at three levels of theory: RHF/3-21G, RHF/6-31G(d), and B3LYP/6-31G(d), on four model systems of the amino acid proline, HCO-Pro-NH2 [I], HCO-Pro-NH-Me [II], MeCO-Pro-NH2 [III], and MeCO-Pro-NH-Me [IV], representing a systematic variation in the protecting N- and C-terminal groups. Three previously located backbone conformations, gammaL, epsilonL, and alphaL, were characterized together with two ring-puckered forms syn (gauche+ = g+) or "DOWN" and anti (gauche- = g-) or "UP", as well as trans-trans, trans-cis, cis-trans, and cis-cis peptide bond isomers. The topologies of the conformational potential energy cross-sections (PECS) of the potential energy hypersurfaces (PEHS) for compounds [I]-[IV] were explored and analyzed in terms of potential energy curves (PEC), and HCO-Pro-NH2 [I] was also analyzed in terms of potential energy surfaces (PESs). Thermodynamic functions were also calculated for HCO-Pro-NH2 [I] at the CBS-4M and G3MP2 levels of theory. The study confirms that the use of the simplest model, compound [I] with P(N) = P(C) = H, along with the RHF/3-21G level of theory, is an acceptable practice for the analysis of peptide models because only minor differences in geometry and stability are observed.