Molecular evolution of P transposable elements in the genus Drosophila. III. The melanogaster species group

Phylogenetic relationships were determined for 76 partial P-element sequences from 14 species of the melanogaster species group within the Drosophila subgenus Sophophora. These results are examined in the context of the phylogeny of the species from which the sequences were isolated. Sequences from the P-element family fall into distinct subfamilies, or clades, which are often characteristic for particular species subgroups. When examined locally among closely related species, the evolution of P elements is characterized by vertical transmission, whereby the P-element phylogeny traces the species phylogeny. On a broader scale, however, the P-element phylogeny is not congruent with the species phylogeny. One feature of P-element evolution in the melanogaster group is the presence of more than one P-element subfamily, differing by as much as 36%, in the genomes of some species. Thus, P elements from several individual species are not monophyletic, and a likely explanation for the incongruence between P-element and species phylogenies is provided by the comparison of paralogous sequences. In certain instances, horizontal transfer seems to be a valid alternative explanation for lack of congruence between species and P-element phylogenies. The canonical P-element subfamily, which represents the active, autonomous transposable element, is restricted to D. melanogaster. Thus, its origin clearly lies outside of the melanogaster species group, consistent with the earlier conclusion of recent horizontal transfer.      

Phylogenetic Relations among Percid Fishes as Inferred from Mitochondrial CytochromebDNA Sequence Data

Hypotheses of relationship among genera of Percidae have been conflicting. Based on different phylogenetic premises, the evolution of small benthic forms in Percidae has been interpreted as resulting from either convergence or common ancestry. In order to assess various phylogenetic hypotheses of Percidae we collected complete sequences (1140 bp) of mitochondrially encoded cytochromebfor 21 species of percids. Seven species representing four additional families of Perciformes were used as outgroups. Maximum parsimony and minimum evolution analyses both recovered single shortest trees, and the results of these analyses were generally congruent with one another. All analyses consistently recovered three monophyletic groups in Percidae: Etheostomatinae (Ammocrypta, Crystallaria, Etheostoma,andPercina), Percinae (PercaandGymnocephalus), and Luciopercinae (Stizostedion, Zingel,andRomanichthys). As a result of this analysis we present a revised classification of Percidae and discuss the phylogenetic evidence for the independent evolution of small benthic species within Etheostomatinae and Luciopercinae.     

Hazard Assessment of Ackee Fruit (Blighia sapida)

Ackee toxicity is associated with consumption of the fruit of the tree Blighia sapida. The problem is endemic in Jamaica, and a number of cases have been reported in the U.S. among Jamaican immigrants. Illness is associated with the method of preparation of the fruit and its ripeness. Malnourished individuals and children appear to be the most susceptible. Levels of the toxic compound, hypoglycin, which are found in the arils and seeds of the fruit, significantly decrease in the arils with ripeness (from 1000 ppm to <0.1?ppm). Symptoms of ackee poisoning in humans occur 6 to 48 hours after ingestion and include vomiting, muscular and mental exhaustion, hypoglycemia, coma and death. Intravenous glucose relieves the hypoglycemia. The most likely mechanism of action occurs through the incorporation of hypoglycin into fatty acid metabolic pathways. Hypoglycin or its primary metabolite methylenecyclopropyl-acetyl-CoA inhibits the oxidation of fatty acids and leucine and the activity of acyl-CoA dehydrogenases. The dose required to elicit acute responses is not known with any precision, nor is it possible to eliminate the likelihood of adverse effects with long-term ingestion of the toxin. Ingestion of unripe aril or pod and seeds represents a significant health hazard; this hazard diminishes considerably with the consumption of properly processed or prepared ripe fruit.     

Similarity of social security numbers among twins: data from the Virginia Twin Registry.

At least two twin registries in the United States have been or are being assembled using the similarity of Social Security Numbers in computerized records to help identify possible twin pairs. While the success of such enterprises depends directly on a high probability of twinness given Social Security Numbers, there are theoretical and practical reasons to study the probability of Social Security Number similarity given twinness. For example, the number of twin pairs with similar Social Security Numbers obviously determines the maximum number of twin pairs that can be discovered by similarity algorithms. To study this issue, we examined the similarity of known Social Security Numbers in twin pairs from the Virginia Twin Registry by age, sex, race, and zygosity of the pair. We found that similarity between the Social Security Numbers of twin pairs varies markedly by age, and MZ twin pairs have significantly more similar Social Security Numbers than DZ pairs at all ages. Among older twins, there are also significant differences by sex and race. For younger twins, algorithms that identify putative twin pairs on the basis of the similarity of their Social Security Numbers hold the promise of being able to identify a large proportion of all true twin pairs. Such algorithms will be substantially less successful, however, in identifying a large proportion of older twin pairs.     

Simple high-performance liquid chromatography method for the simultaneous determination of serum caffeine and paraxanthine following rapid sample preparation

A simple reversed-phase high-performance liquid chromatography (HPLC) method for the simultaneous determination of caffeine and paraxanthine in human serum is described. Serum proteins are precipitated with perchloric acid and the resulting supernatant neutralized for direct injection onto an HPLC column. The method uses a phosphate–methanol mobile phase (85:15, v/v) at pH 4.9 with a flow-rate of 1.75 ml/min and quantitation is by UV absorbance at 274 nm. Elution times are approximately 18 min for caffeine and 8 min for paraxanthine. Theobromine and theophylline have elution times of 5.4 and 9.4 min and do not interfere in the assay. The intra-assay and between-assay means for precision and accuracy for both drugs are: 4.5% C.V. and 3.3% deviation. The sensitivity of the method is 50 ng/ml for each drug.     

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial

BackgroundAntenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care.Methods and findingsThis was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24⁺¹ weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster–summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) −6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes.ConclusionsIn this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings.Trial registrationThis trial is registered with the ISRCTN registry, ISRCTN67698474.

Matias C Vieira and colleagues evaluate the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age in the DESiGN cluster randomised trial.     

Marker-free method for accurate alignment between correlated light,cryo-light,and electron cryo-microscopy data using sample support features

Combining fluorescence microscopy with electron cryo-tomography allows, in principle, spatial localization of tagged macromolecular assemblies and structural features within the cellular environment. To allow precise localization and scale integration between the two disparate imaging modalities, accurate alignment procedures are needed. Here, we describe a marker-free method for aligning images from light or cryo-light fluorescence microscopy and from electron cryo-microscopy that takes advantage of sample support features, namely the holes in the carbon film. We find that the accuracy of this method, as judged by prediction errors of the hole center coordinates, is better than 100?nm.     

The Burden Attributable to Mental and Substance Use Disorders as Risk Factors for Suicide: Findings from the Global Burden of Disease Study 2010

Background

The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5^th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010''s mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders.

Methods

Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty).

Results

Mental and substance use disorders were responsible for 22.5 million (14.8–29.8 million) of the 36.2 million (26.5–44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%–60.8%)) and anorexia nervosa the lowest (0.2% (0.02%–0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20–30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%–8.6%) to 8.3% (7.1%–9.6%) of global DALYs, and would have changed the global ranking from 5^th to 3^rd leading cause of burden.

Conclusions

Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.