Student biocuration projects as a learning environment

BACKGROUND: Bioinformatics is becoming an essential tool for the majority of biological and biomedical researchers. Although bioinformatics data is exploited by academic and industrial researchers, limited focus is on teaching this area to undergraduates, postgraduates and senior scientists. Many scientists are developing their own expertise without formal training and often without appreciating the source of the data they are reliant upon. Some universities do provide courses on a variety of bioinformatics resources and tools, a few also provide biocuration projects, during which students submit data to annotation resources. METHODS: To assess the usefulness and enjoyability of annotation projects a survey was sent to University College London (UCL) students who have undertaken Gene Ontology biocuration projects. RESULTS: Analysis of survey responses suggest that these projects provide students with an opportunity not only to learn about bioinformatics resources but also to improve their literature analysis, presentation and writing skills. CONCLUSIONS: Biocuration student projects provide valuable annotations as well as enabling students to develop a variety of skills relevant to their future careers. It is also hoped that, as future scientists, these students will critically assess their own manuscripts and ensure that these are written with the biocurators of the future in mind

Demethylation of the Coding Region Triggers the Activation of the Human Testis-Specific PDHA2 Gene in Somatic Tissues

Human PDHA2 is a testis-specific gene that codes for the E1α subunit of Pyruvate Dehydrogenase Complex (PDC), a crucial enzyme system in cell energy metabolism. Since activation of the PDHA2 gene in somatic cells could be a new therapeutic approach for PDC deficiency, we aimed to identify the regulatory mechanisms underlying the human PDHA2 gene expression. Functional deletion studies revealed that the −122 to −6 promoter region is indispensable for basal expression of this TATA-less promoter, and suggested a role of an epigenetic program in the control of PDHA2 gene expression. Indeed, treatment of SH-SY5Y cells with the hypomethylating agent 5-Aza-2′-deoxycytidine (DAC) promoted the reactivation of the PDHA2 gene, by inducing the recruitment of the RNA polymerase II to the proximal promoter region and the consequent increase in PDHA2 mRNA levels. Bisulfite sequencing analysis revealed that DAC treatment induced a significant demethylation of the CpG island II (nucleotides +197 to +460) in PDHA2 coding region, while the promoter region remained highly methylated. Taken together with our previous results that show an in vivo correlation between PDHA2 expression and the demethylation of the CpG island II in testis germ cells, the present results show that internal methylation of the PDHA2 gene plays a part in its repression in somatic cells. In conclusion, our data support the novel finding that methylation of the PDHA2 coding region can inhibit gene transcription. This represents a key mechanism for absence of PDHA2 expression in somatic cells and a target for PDC therapy

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

The effect of maternal common mental disorders on infant undernutrition in Butajira, Ethiopia: The P-MaMiE study

BACKGROUND: Although maternal common mental disorder (CMD) appears to be a risk factor for infant undernutrition in South Asian countries, the position in sub-Saharan Africa (SSA) is unclear METHODS: A population-based cohort of 1065 women, in the third trimester of pregnancy, was identified from the demographic surveillance site (DSS) in Butajira, to investigate the effect of maternal CMD on infant undernutrition in a predominantly rural Ethiopian population. Participants were interviewed at recruitment and at two months post-partum. Maternal CMD was measured using the locally validated Self-Reported Questionnaire (score of > or = six indicating high levels of CMD). Infant anthropometry was recorded at six and twelve months of age. RESULT: The prevalence of CMD was 12% during pregnancy and 5% at the two month postnatal time-point. In bivariate analysis antenatal CMD which had resolved after delivery predicted underweight at twelve months (OR = 1.71; 95% CI: 1.05, 2.50). There were no other statistically significant differences in the prevalence of underweight or stunted infants in mothers with high levels of CMD compared to those with low levels. The associations between CMD and infant nutritional status were not significant after adjusting for pre-specified potential confounders. CONCLUSION: Our negative finding adds to the inconsistent picture emerging from SSA. The association between CMD and infant undernutrition might be modified by study methodology as well as degree of shared parenting among family members, making it difficult to extrapolate across low- and middle-income countries