Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.     

Cohesin component dynamics during meiotic prophase I in mammalian oocytes

Cohesins are chromosomal proteins that form complexes involved in the maintenance of sister chromatid cohesion during division of somatic and germ cells. Three meiosis-specific cohesin subunits have been reported in mammals, REC8, STAG3 and SMC1 beta; their expression in mouse spermatocytes has also been described. Here we studied the localization of different meiotic and mitotic cohesin components during prophase I in human and murine female germ cells. In normal and atretic human fetal oocytes, from leptotene to diplotene stages, REC8 and STAG3 colocalize in fibers. In murine oocytes, SMC1beta, SMC3 and STAG3 are localized along fibers that correspond first to the chromosome axis and then to the synaptonemal complex in pachytene. Mitotic cohesin subunit RAD21 is also found in fibers that decorate the SC during prophase I in mouse oocytes, suggesting a role for this cohesin in mammalian sister chromatid cohesion in female meiosis. We observed that, unlike human oocytes, murine synaptonemal complex protein SYCP3 localizes to nucleoli throughout prophase I stages, and centromeres cluster in discrete locations from leptotene to dictyate. At difference from meiosis in male mice, the cohesin axis is progressively lost during the first week after birth in females with a parallel destruction of the axial elements at dictyate arrest, demonstrating sexual dimorphism in sister chromatid cohesion in meiosis.     

The sympathetic innervation of the internal anal sphincter and rectum in the cat

The distribution of the sympathetic innervation to the internal anal sphincter (IAS) and rectum and the occurrence of different types of adrenergic receptors in the two organs were investigated in anaesthetized cats. Anal pressure and rectal motility were recorded by a manometric and a volumetric method respectively. Division of both the hypogastric nerves (HGN) and the lumbar colonic nerves (LCN) reduced the anal pressure by 46 +/- 6% of the resting pressure (40.9 +/- 6.4 mmHg) and consistently increased rectal motility. Efferent electrical stimulation of the HGN as well as the LCN elicited a contraction in the anus and the rectum, which, at maximal stimulation, caused the anal pressure to reach a similar level to that recorded before division of these nerves. After injection of phentolamine the anal contraction was abolished, whereas the rectal contraction was either abolished or converted to a beta-adrenergic relaxation. Propranolol caused increased rectal contraction in response to stimulation of the HGN and the LCN, whereas the anal contraction was unaffected. The results imply that the sympathetic nerves exert a tonic excitatory effect on the IAS and a dual effect on the rectum in the cat. The results also indicate that sympathetic fibres to the IAS are conveyed in both the HGN and the LCN. Inhibitory beta-adrenergic receptors seem to be of minor importance in regulating anal pressure.     

Evaluating Differences in Whole Blood,Serum, and Urine Screening Tests for Zika Virus,Puerto Rico,USA, 2016

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015–2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.     

Factors That Predict 1-Year Incident Hip and Non-Hip Fractures for Home Care Recipients: A Linked-Data Retrospective Cohort Study

ObjectivesThe purpose of our study was to identify factors that predict 1-year incident hip and major osteoporotic non-hip fractures (ie, wrist, spine, pelvis, humerus) for home care recipients while accounting for the competing risk of death.DesignWe conducted a retrospective cohort study with linked population data.Setting and ParticipantsAll home care recipients in Ontario, Canada, receiving services for more than 6 months with an admission assessment between April 1, 2011, and March 31, 2015, were included.MethodsClinical data from the Resident Assessment Instrument Home Care were linked to fracture data from the Discharge Abstract Database and the National Acute Care Reporting System. Competing risk proportional hazard regressions using the Fine and Grey method were performed to model the association between potential risk factors and fracture.ResultsPrevious fall, previous fracture, cognitive impairment, unsteady gait, alcohol use, tobacco use, and Parkinson disease were consistently associated with all fracture types. Cognitive impairment (hazard ratio 2.09; 95% confidence interval 1.86–2.36) and wandering [1.66 (1.06–1.27)] were most predictive of hip fractures and being female [1.86 (1.76–1.98)] and experiencing a previous fracture [1.86 (1.76–1.98)] were most predictive of non-hip fractures. Risk factors unique to non-hip fractures as compared with hip fractures were locomotion ability outdoors and psychotropic medication use.Conclusions and ImplicationsOur results indicate that, in addition to typical fracture risk factors, home care recipients have unique characteristics that increase their risk. Fracture risk assessment tools and subsequent prevention strategies should be modified to accurately identify home care recipients at risk for imminent 1-year fracture.     

Thumbprinting Locally Advanced Pancreatic Cancer: Have We Developed the Optimal Staging System?

Annals of Surgical Oncology -