The budding yeast Wee1 kinase Swe1 restrains the metaphase-to-anaphase transition by preventing the Cdk1-dependent phosphorylation and activation of APCCdc20.

Background and objectives Prescribed exercise to treat medical conditions and to prepare for surgery is a promising intervention to prevent adverse health outcomes for older adults; however, adherence to exercise programs may be low. Our objective was to identify and grade the quality of predictors of adherence to prescribed exercise in older adults. Methods Prospective observational and experimental studies were identified using a peer-reviewed search strategy applied to MEDLINE, EMBASE, Cochrane, and CINAHL from inception until October 6, 2020. Following an independent and duplicate review of titles, abstracts, and full texts, we included prospective studies with an average population age >65 years, where exercise was formally prescribed for a medical or surgical condition. We excluded studies where exercise was prescribed for a chronic musculoskeletal condition. Risk of bias was assessed using the Quality in Prognostic studies tool or Cochrane risk of bias tool, as appropriate. Predictors of adherence were identified and graded for quality using an adaptation of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for predictor studies. Results We included 19 observational studies and 4 randomized controlled trials (n=5785) Indications for exercise included cardiac (n=6), pulmonary rehabilitation (n=7), or other (n=10; surgical, medical, and neurologic). Of the 10 studies that reported adherence as the percent of prescribed sessions completed, average adherence was 80% (range 60–98%; standard deviation (SD) 11%). Of the 10 studies that reported adherence as a categorical threshold demarking adherent vs not adherent, average adherence was 57.5% (range 21–83%; SD 21%). Moderate-quality evidence suggested that positive predictors of adherence were self-efficacy and good self-rated mental health; negative predictors were depression (high quality) and distance from the exercise facility. Moderate-quality evidence suggested that comorbidity and age were not predictive of adherence. Conclusions These findings can inform the design of future exercise programs as well as the identification of individuals who may require extra support to benefit from prescribed exercise. Systematic review registration PROSPERO CRD42018108242

Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits.

Changes in the locations and boundaries of heterochromatin are critical during development, and de novo assembly of silent chromatin in budding yeast is a well-studied model for how new sites of heterochromatin assemble. De novo assembly cannot occur in the G1 phase of the cell cycle and one to two divisions are needed for complete silent chromatin assembly and transcriptional repression. Mutation of DOT1, the histone H3 lysine 79 (K79) methyltransferase, and SET1, the histone H3 lysine 4 (K4) methyltransferase, speed de novo assembly. These observations have led to the model that regulated demethylation of histones may be a mechanism for how cells control the establishment of heterochromatin. We find that the abundance of Sir4, a protein required for the assembly of silent chromatin, decreases dramatically during a G1 arrest and therefore tested if changing the levels of Sir4 would also alter the speed of de novo establishment. Halving the level of Sir4 slows heterochromatin establishment, while increasing Sir4 speeds establishment. yku70Δ and ubp10Δ cells also speed de novo assembly, and like dot1Δ cells have defects in subtelomeric silencing, suggesting that these mutants may indirectly speed de novo establishment by liberating Sir4 from telomeres. Deleting RIF1 and RIF2, which suppresses the subtelomeric silencing defects in these mutants, rescues the advanced de novo establishment in yku70Δ and ubp10Δ cells, but not in dot1Δ cells, suggesting that YKU70 and UBP10 regulate Sir4 availability by modulating subtelomeric silencing, while DOT1 functions directly to regulate establishment. Our data support a model whereby the demethylation of histone H3 K79 and changes in Sir4 abundance and availability define two rate-limiting steps that regulate de novo assembly of heterochromatin.