DNA methylation in mouse embryonic stem cells and development

Mammalian development is associated with considerable changes in global DNA methylation levels at times of genomic reprogramming. Normal DNA methylation is essential for development but, despite considerable advances in our understanding of the DNA methyltransferases, the reason that development fails when DNA methylation is deficient remains unclear. Furthermore, although much is known about the enzymes that cause DNA methylation, comparatively little is known about the mechanisms or significance of active demethylation in early development. In this review, we discuss the roles of the various DNA methyltransferases and their likely functions in development.     

Evaluation of a fully automated method to measure the critical removal stress of adult barnacles

A computer-controlled force gauge designed to measure the adhesive strength of barnacles on test substrata is described. The instrument was evaluated with adult barnacles grown in situ on Silastic T2(R)-coated microscope slides and epoxy replicas adhered to the same substratum with synthetic adhesive. The force per unit area required to detach the barnacles (critical removal stress) using the new automated system was comparable to that obtained with ASTM D5618 (1994) (0.19 and 0.28 MPa compared with 0.18 and 0.27 MPa for two batches of barnacles). The automated method showed a faster rate of force development compared with the manual spring force gauge used for ASTM D5618 (1994). The new instrument was as accurate and precise at determining surface area as manual delineation used with ASTM D5618 (1994). The method provided significant advantages such as higher throughput speed, the ability to test smaller barnacles (which took less time to grow) and to control the force application angle and speed. The variability in measurements was lower than previously reported, suggesting an improved ability to compare the results obtained by different researchers.     

Molecular basis of resistance to cytochrome bc1 inhibitors

Inhibitors of the mitochondrial respiratory chain enzyme cytochrome bc ₁ (respiratory complex III) have been developed as antimicrobial agents. They are used in agriculture to control plant pathogenic fungi and in medicine against human pathogens, such as the malaria parasite Plasmodium falciparum , or Pneumocystis jiroveci (an opportunistic pathogenic fungus life-threatening in immuno-compromised patients). These respiratory inhibitors are thus effective against a broad range of important pathogens. Unfortunately, the problem of acquired resistance has rapidly emerged. A growing number of pathogen isolates resistant to inhibitor treatment have been reported, and this resistance is often linked to mutation within cytochrome b , one of the essential catalytic subunits of the complex. Saccharomyces cerevisiae is an invaluable model in order to assess the impact of the mutations on the sensitivity to the drugs, on the respiratory capacity and the fitness of cells. In this minireview, the inhibitors, their mode of action, and the mutations implicated in resistance and studied in yeast are briefly reviewed. Four mutations that are of particular importance in medicine and in agriculture are briefly reviewed and described in more detail and the molecular basis of resistance and of evolution of the mutations is discussed succinctly.     

Determination and validation of principal gene products

MOTIVATION: Alternative splicing has the potential to generate a wide range of protein isoforms. For many computational applications and for experimental research, it is important to be able to concentrate on the isoform that retains the core biological function. For many genes this is far from clear. RESULTS: We have combined five methods into a pipeline that allows us to detect the principal variant for a gene. Most of the methods were based on conservation between species, at the level of both gene and protein. The five methods used were the conservation of exonic structure, the detection of non-neutral evolution, the conservation of functional residues, the existence of a known protein structure and the abundance of vertebrate orthologues. The pipeline was able to determine a principal isoform for 83% of a set of well-annotated genes with multiple variants.     

Does perceived financial strain predict depression among young women? Longitudinal findings from the Southampton Women's Survey

Background Social and financial environment has an influence on the incidence of depression. We studied perceived financial strain as a risk factor for development of depression among a large cohort of young women in Southampton, UK.Methods We recruited a large number of young women in Southampton in the Southampton Women's Survey, a longitudinal study looking at factors influencing the health of women and their offspring. Women were asked to complete a baseline questionnaire, which included the GHQ-12 (an assessment of mental health), as well as questions on perceived financial strain and past history of depression. They were followed up two years later through their general practitioner (GP) records for evidence of incident mental illness.Results A total of 7020 women completed the baseline questionnaire including the GHQ-12. Of these, 5237 (74.6%) had records available for follow-up. Among those developing depression, there was a higher proportion receiving benefits, and a higher level of perceived financial strain. There were also modest elevations in perceived stress, and poorer levels of educational attainment. Among women not depressed at baseline, and with no previous history of depression, those in receipt of state benefits at baseline had a significantly elevated risk of developing the disorder - hazard ratio 1.61 (95% confidence interval (CI) 1.13-2.3). The risk associated with perceived financial strain was 2.16 (95% CI 1.14-4.11), but this did not remain statistically significant after adjustment was made for receipt of benefits, educational qualification, and perceived stress.Conclusion Financial hardship as evidenced by receipt of benefits is a strong independent predictor for the development of depression. Although perception of financial strain is also a predictor for incident depression, the risk associated with this subjective characteristic does not remain significantly elevated after adjustment. Future studies of the aetiology of depression should incorporate ascertainment of actual financial status.     

Population assessment using multivariate time‐series analysis: A case study of rockfishes in Puget Sound

Estimating a population's growth rate and year‐to‐year variance is a key component of population viability analysis (PVA ). However, standard PVA methods require time series of counts obtained using consistent survey methods over many years. In addition, it can be difficult to separate observation and process variance, which is critical for PVA . Time‐series analysis performed with multivariate autoregressive state‐space (MARSS ) models is a flexible statistical framework that allows one to address many of these limitations. MARSS models allow one to combine surveys with different gears and across different sites for estimation of PVA parameters, and to implement replication, which reduces the variance‐separation problem and maximizes informational input for mean trend estimation. Even data that are fragmented with unknown error levels can be accommodated. We present a practical case study that illustrates MARSS analysis steps: data choice, model set‐up, model selection, and parameter estimation. Our case study is an analysis of the long‐term trends of rockfish in Puget Sound, Washington, based on citizen science scuba surveys, a fishery‐independent trawl survey, and recreational fishery surveys affected by bag‐limit reductions. The best‐supported models indicated that the recreational and trawl surveys tracked different, temporally independent assemblages that declined at similar rates (an average of ?3.8% to ?3.9% per year). The scuba survey tracked a separate increasing and temporally independent assemblage (an average of 4.1% per year). Three rockfishes (bocaccio, canary, and yelloweye) are listed in Puget Sound under the US Endangered Species Act (ESA ). These species are associated with deep water, which the recreational and trawl surveys sample better than the scuba survey. All three ESA ‐listed rockfishes declined as a proportion of recreational catch between the 1970s and 2010s, suggesting that they experienced similar or more severe reductions in abundance than the 3.8–3.9% per year declines that were estimated for rockfish populations sampled by the recreational and trawl surveys.