Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans

This is the final version. Available on open access from Nature Research via the DOI in this recordData Availability: The data that support the findings of this study from the UK BioBank will be made available at https://sleepgenetics.org and the underlying genotype and phenotype data are available through application to the UK Biobank. Other phenotype data are available on request, due to privacy or other restrictions, through co-corresponding author Dr. Scheer ([email protected]).The PERIOD2 (PER2) gene is a core molecular component of the circadian clock and plays an important role in the generation and maintenance of daily rhythms. rs35333999, a missense variant of PER2 common in European populations, has been shown to associate with later chronotype. Chronotype relates to the timing of biological and behavioral activities, including when we sleep, eat, and exercise, and later chronotype is associated with longer intrinsic circadian period (cycle length), a fundamental property of the circadian system. Thus, we tested whether this PER2 variant was associated with circadian period and found significant associations with longer intrinsic circadian period as measured under forced desynchrony protocols, the ‘gold standard’ for intrinsic circadian period assessment. Minor allele (T) carriers exhibited significantly longer circadian periods when determinations were based on either core body temperature or plasma melatonin measurements, as compared to non-carriers (by 12 and 11 min, respectively; accounting for ~7% of inter-individual variance). These findings provide a possible underlying biological mechanism for inter-individual differences in chronotype, and support the central role of PER2 in the human circadian timing system.European CommissionWellcome TrustMedical Research Council (MRC

District nurses' perspectives on detecting mental health problems and promoting mental health among community-dwelling seniors with multimorbidity

AIMS AND OBJECTIVES: To describe district nurses' perspectives on detecting mental health problems and promoting mental health among homebound older people with multimorbidity. BACKGROUND: Mental health problems among older people with multiple chronic conditions, that is, multimorbidity, are challenging issues. These patients' homes often serve as arenas in which district nurses can promote health. Mental health promotion must be studied in greater depth within primary care because older people with multimorbidity are particularly prone to developing poor mental health, which can go undetected and untreated. DESIGN: A descriptive, qualitative study using semi-structured interviews and content analysis. METHODS: Twenty-five district nurses completed individual or focus group interviews. Data were analysed using qualitative content analysis. RESULTS: Most district nurses stated that detecting mental health problems and promoting mental health were important tasks but that they typically focused on more practical home health care tasks. The findings revealed that district nurses focused on assessment, collaboration and social support as means of detecting mental health problems and promoting mental health. CONCLUSIONS: The district nurses described various factors and actions that appeared to be important prerequisites for their involvement in primary mental health care. Nevertheless, there were no established goals for mental health promotion, and district nurses often seemed to depend on their collaboration with other actors. Our findings indicated that district nurses cannot bear the primary responsibility for the early detection of mental health problems and early interventions to promote mental health within this population. RELEVANCE TO CLINICAL PRACTICE: The findings of this study indicated that workforce training and collaboration between different care providers are important elements in the future development of this field. Early detection and early treatment of mental health-related issues should also be stated as explicit objectives in the provision of care to community-dwelling older people with multimorbidity

DNA Methylation of the Gonadal Aromatase (cyp19a) Promoter Is Involved in Temperature-Dependent Sex Ratio Shifts in the European Sea Bass

Sex ratio shifts in response to temperature are common in fish and reptiles. However, the mechanism linking temperature during early development and sex ratios has remained elusive. We show in the European sea bass (sb), a fish in which temperature effects on sex ratios are maximal before the gonads form, that juvenile males have double the DNA methylation levels of females in the promoter of gonadal aromatase (cyp19a), the enzyme that converts androgens into estrogens. Exposure to high temperature increased the cyp19a promoter methylation levels of females, indicating that induced-masculinization involves DNA methylation-mediated control of aromatase gene expression, with an observed inverse relationship between methylation levels and expression. Although different CpGs within the sb cyp19a promoter exhibited different sensitivity to temperature, we show that the increased methylation of the sb cyp19a promoter, which occurs in the gonads but not in the brain, is not a generalized effect of temperature. Importantly, these effects were also observed in sexually undifferentiated fish and were not altered by estrogen treatment. Thus, methylation of the sb cyp19a promoter is the cause of the lower expression of cyp19a in temperature-masculinized fish. In vitro, induced methylation of the sb cyp19a promoter suppressed the ability of SF-1 and Foxl2 to stimulate transcription. Finally, a CpG differentially methylated by temperature and adjacent to a Sox transcription factor binding site is conserved across species. Thus, DNA methylation of the aromatase promoter may be an essential component of the long-sought-after mechanism connecting environmental temperature and sex ratios in vertebrate species with temperature-dependent sex determination