2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

The Expert Panel was charged with using data from randomized controlled trials (RCTs) and systematic reviews and meta-analyses of RCTs to update the clinical practice recommendations for the treatment of blood cholesterol levels to reduce ASCVD risk. For this guideline, ASCVD includes coronary heart disease (CHD), stroke, and peripheral arterial disease, all of presumed atherosclerotic origin. These recommendations are intended to provide a strong, evidence-based foundation for the treatment of cholesterol for the primary and secondary prevention of ASCVD in women and men

Bub1-Mediated Adaptation of the Spindle Checkpoint

During cell division, the spindle checkpoint ensures accurate chromosome segregation by monitoring the kinetochore–microtubule interaction and delaying the onset of anaphase until each pair of sister chromosomes is properly attached to microtubules. The spindle checkpoint is deactivated as chromosomes start moving toward the spindles in anaphase, but the mechanisms by which this deactivation and adaptation to prolonged mitotic arrest occur remain obscure. Our results strongly suggest that Cdc28-mediated phosphorylation of Bub1 at T566 plays an important role for the degradation of Bub1 in anaphase, and the phosphorylation is required for adaptation of the spindle checkpoint to prolonged mitotic arrest

Scaling matters: incorporating body composition into Weddell seal seasonal oxygen store comparisons reveals maintenance of aerobic capacities

Adult Weddell seals (Leptonychotes weddellii) haul-out on the ice in October/November (austral spring) for the breeding season and reduce foraging activities for ~4 months until their molt in the austral fall (January/February). After these periods, animals are at their leanest and resume actively foraging for the austral winter. In mammals, decreased exercise and hypoxia exposure typically lead to decreased production of O2-carrying proteins and muscle wasting, while endurance training increases aerobic potential. To test whether similar effects were present in marine mammals, this study compared the physiology of 53 post-molt female Weddell seals in the austral fall to 47 pre-breeding females during the spring in McMurdo Sound, Antarctica. Once body mass and condition (lipid) were controlled for, there were no seasonal changes in total body oxygen (TBO2) stores. Within each season, hematocrit and hemoglobin values were negatively correlated with animal size, and larger animals had lower mass-specific TBO2 stores. But because larger seals had lower mass-specific metabolic rates, their calculated aerobic dive limit was similar to smaller seals. Indicators of muscular efficiency, myosin heavy chain composition, myoglobin concentrations, and aerobic enzyme activities (citrate synthase and β-hydroxyacyl CoA dehydrogenase) were likewise maintained across the year. The preservation of aerobic capacity is likely critical to foraging capabilities, so that following the molt Weddell seals can rapidly regain body mass at the start of winter foraging. In contrast, muscle lactate dehydrogenase activity, a marker of anaerobic metabolism, exhibited seasonal plasticity in this diving top predator and was lowest after the summer period of reduced activity

Multiple tandemly repeated binding sites for cellular nuclear factor 1 that surround the major immediate-early promoters of simian and human cytomegalovirus.

We show that the large DNA genomes of human and simian cytomegaloviruses (HCMV and SCMV, respectively) each contain multiple binding sites for purified cellular nuclear factor 1 (NF1) protein. Examination of the major immediate-early (IE) gene region in the HindIII H fragment of SCMV (Colburn) by filter binding assays showed that it competed 45-fold better than the single adenovirus type 2 binding site for NF1 protein and that it contained at least two distinct binding loci. Direct DNase I footprinting analyses of the 5' upstream locus detected at least 20 adjacent NF1-binding sites located between positions -600 and -1300 relative to the IE94 mRNA start site. DNA sequence analysis of the region revealed a conserved consensus NF1 recognition element (T)TGG(C/A)N5GCCAA embedded within each of 23 highly diverged 30-base-pair tandem repeats, together with a second downstream cluster of five consensus NF1-binding sites between positions +470 and +570 in the large first intron. Two separate NF1-binding loci were also found in the equivalent IE68 gene of HCMV(Towne) DNA, but in this case the DNA sequence and competition filter binding experiments indicated a maximum of only four to five consensus binding sites encompassing the promoter-enhancer region. In transient expression assays, neither the isolated upstream IE94 tandem repeats nor a synthetic single-copy consensus NF1-binding site acted as transcriptional cis activators or enhancers when placed adjacent to the simian virus 40 minimal early region promoter. We conclude that the large and complex 5' upstream promoter-regulatory region for the SCMV IE94 gene comprises two distinct domains. The previously described four sets of 13- to 18-base-pair interspersed repeat elements between -55 and -580 provide most of the high basal transcriptional strength, whereas the arrangement of further upstream tandemly repeated NF1-binding sites may contribute significantly to the expanded biological host range for expression of SCMV IE94 compared with HCMV IE68