Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons

Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability

Novel Gene Acquisition on Carnivore Y Chromosomes

Despite its importance in harboring genes critical for spermatogenesis and male-specific functions, the Y chromosome has been largely excluded as a priority in recent mammalian genome sequencing projects. Only the human and chimpanzee Y chromosomes have been well characterized at the sequence level. This is primarily due to the presumed low overall gene content and highly repetitive nature of the Y chromosome and the ensuing difficulties using a shotgun sequence approach for assembly. Here we used direct cDNA selection to isolate and evaluate the extent of novel Y chromosome gene acquisition in the genome of the domestic cat, a species from a different mammalian superorder than human, chimpanzee, and mouse (currently being sequenced). We discovered four novel Y chromosome genes that do not have functional copies in the finished human male-specific region of the Y or on other mammalian Y chromosomes explored thus far. Two genes are derived from putative autosomal progenitors, and the other two have X chromosome homologs from different evolutionary strata. All four genes were shown to be multicopy and expressed predominantly or exclusively in testes, suggesting that their duplication and specialization for testis function were selected for because they enhance spermatogenesis. Two of these genes have testis-expressed, Y-borne copies in the dog genome as well. The absence of the four newly described genes on other characterized mammalian Y chromosomes demonstrates the gene novelty on this chromosome between mammalian orders, suggesting it harbors many lineage-specific genes that may go undetected by traditional comparative genomic approaches. Specific plans to identify the male-specific genes encoded in the Y chromosome of mammals should be a priority

Folate status and socio‐demographic predictors of folate status, among a national cohort of women aged 26–36 in Australia, 2004–2006

Abstract Objective : To describe serum folate status and the socio‐demographic correlates of serum folate status in a national sample of women aged 26–36 years in Australia, 2004–2006. Methods: Stored serum samples from 1,046 women, collected as part of the Childhood Determinants of Adult Health study, were analysed for serum folate. Results: Median (IQR) serum folate was 27.1 nmol/L (18.8–35.0 nmol/L) with only 7.0% of samples below 11 nmol/L. Serum folate was positively associated with supplement use, educational level, occupational status and urban dwelling. Conclusions: In this population‐based sample, most women had folate levels in the normal range with few having low serum folate. Those of lower socioeconomic position or with poorer health behaviours had lower folate levels, though most were still within the normal range. Implications: In the absence of comprehensive national survey data on the folate status of women of child‐bearing age, these data provide a valuable baseline for evaluating the impact of mandatory folic acid fortification in Australia, which commenced in 2009. It is likely that mandatory fortification of the food supply with folic acid will reduce the disparities in folate status between socioeconomic groups and in people with poorer health behaviours

Prevalence and correlates of psychological distress in a large and diverse public sector workforce: Baseline results from Partnering Healthy@Work

Background: Depressive and anxiety disorders are common among working adults and costly to employers and individuals. Mental health screening is often an important initial strategy, but the resultant data are often of unknown representativeness and difficult to interpret. In a public sector workforce, this study used a brief screener for depression/anxiety to: a) compare prevalence of high psychological distress obtained from a researcher survey with an employer survey and population norms and b) verify whether expected correlates were observed in a screening setting. Methods. Participants were public servants working for an Australian state government. High psychological distress (Kessler-10 ≥22) stratified by age and sex was compared for a random weighted sample researcher survey (n = 3406) and an anonymous volunteer employer survey (n = 7715). Prevalence ratios (PR) were estimated from log binomial regression. Results: Referencing the researcher survey, prevalence of high psychological distress was greater by age and sex in the employer survey but was only dependably higher for men when compared with population norms. Modelling suggested this may be due to work stress (effort-reward imbalance) (PR = 3.19, 95% CI 1.45-7.01) and casual/fixed-term employment (PR 2.64, 95% CI 1.26-5.56). Conclusions: Depression and anxiety screening using typical employer survey methods could overestimate prevalence but expected correlates are observed in a screening setting. Guidance for employers on screening and interpretation should be provided to encourage engagement with mental health prevention and treatment programs in the workplace

Trends in rates of mental illness in homicide perpetrators

BackgroundThe rise in homicides by those with serious mental illness is of concern, although this increase may not be continuing.AimsTo examine rates of mental illness among homicide perpetrators.MethodA national consecutive case series of homicide perpetrators in England and Wales from 1997 to 2006. Rates of mental disorder were based on data from psychiatric reports, contact with psychiatric services, diminished responsibility verdict and hospital disposal.ResultsOf the 5884 homicides notified to the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness between 1997 and 2006, the number of homicide perpetrators with schizophrenia increased at a rate of 4% per year, those with psychotic symptoms at the time of the offence increased by 6% per year. The number of verdicts of diminished responsibility decreased but no change was found in the number of perpetrators receiving a hospital order disposal. The likeliest explanation for the rise in homicide by people with psychosis is the misuse of drugs and/or alcohol, which our data show increased at a similar magnitude to homicides by those with psychotic symptoms. However, we are unable to demonstrate a causal association. Although the Poisson regression provides evidence of an upward trend in homicide by people with serious mental illness between 1997 and 2006, the number of homicides fell in the final 2 years of data collection, so these findings should be treated with caution.ConclusionsThere appears to be a concomitant increase in drug misuse over the period, which may account for this rise in homicide. However, an increase in the number of people in contact with mental health services may suggest that access to mental health services is improving. Previous studies have used court verdicts such as diminished responsibility as a proxy measure of mental disorder. Our data indicate that this does not reflect accurately the prevalence of mental disorder in this population.</jats:sec