Cooperative and Antagonistic Contributions of Two Heterochromatin Proteins to Transcriptional Regulation of the Drosophila Sex Determination Decision

Eukaryotic nuclei contain regions of differentially staining chromatin (heterochromatin), which remain condensed throughout the cell cycle and are largely transcriptionally silent. RNAi knockdown of the highly conserved heterochromatin protein HP1 in Drosophila was previously shown to preferentially reduce male viability. Here we report a similar phenotype for the telomeric partner of HP1, HOAP, and roles for both proteins in regulating the Drosophila sex determination pathway. Specifically, these proteins regulate the critical decision in this pathway, firing of the establishment promoter of the masterswitch gene, Sex-lethal (Sxl). Female-specific activation of this promoter, SxlPe, is essential to females, as it provides SXL protein to initiate the productive female-specific splicing of later Sxl transcripts, which are transcribed from the maintenance promoter (SxlPm) in both sexes. HOAP mutants show inappropriate SxlPe firing in males and the concomitant inappropriate splicing of SxlPm-derived transcripts, while females show premature firing of SxlPe. HP1 mutants, by contrast, display SxlPm splicing defects in both sexes. Chromatin immunoprecipitation assays show both proteins are associated with SxlPe sequences. In embryos from HP1 mutant mothers and Sxl mutant fathers, female viability and RNA polymerase II recruitment to SxlPe are severely compromised. Our genetic and biochemical assays indicate a repressing activity for HOAP and both activating and repressing roles for HP1 at SxlPe

Illness uncertainty and treatment motivation in type 2 diabetes patients

AIMS: To characterize the uncertainty in illness and the motivation for treatment and to evaluate the existing relation between these variables in individuals with type 2 diabetes. METHOD: Descriptive, correlational study, using a sample of 62 individuals in diabetes consultation sessions. The Uncertainty Stress Scale and the Treatment Self-Regulation Questionnaire were used. RESULTS: The individuals with type 2 diabetes present low levels of uncertainty in illness and a high motivation for treatment, with a stronger intrinsic than extrinsic motivation. A negative correlation was verified between the uncertainty in the face of the prognosis and treatment and the intrinsic motivation. DISCUSSION: These individuals are already adapted, acting according to the meanings they attribute to illness. Uncertainty can function as a threat, intervening negatively in the attribution of meaning to the events related to illness and in the process of adaptation and motivation to adhere to treatment. Intrinsic motivation seems to be essential to adhere to treatment