Fertilization triggers significant cellular remodeling through the oocyte-to-embryo transition. In this transition, the ubiquitin-proteasome system and autophagy are essential for the degradation of maternal components; however, the significance of degradation of cell surface components remains unknown. In this study, we show that multiple maternal plasma membrane proteins, such as the glycine transporter GlyT1a, are selectively internalized from the plasma membrane to endosomes in mouse embryos by the late two-cell stage and then transported to lysosomes for degradation at the later stages. During this process, large amounts of ubiquitylated proteins accumulated on endosomes. selleck inhibitor Furthermore, the degradation of GlyT1a with mutations in potential ubiquitylation sites was delayed, suggesting that ubiquitylation may be involved in GlyT1a degradation. The clathrin inhibitor blocked GlyT1a internalization. Strikingly, the protein kinase C (PKC) activator triggered the heterochronic internalization of GlyT1a; the PKC inhibitor markedly blocked GlyT1a endocytosis. Lastly, clathrin inhibition completely blocked embryogenesis at the two-cell stage and inhibited cell division after the four-cell stage. These findings demonstrate that PKC-dependent clathrin-mediated endocytosis is essential for the selective degradation of maternal membrane proteins during oocyte-to-embryo transition and early embryogenesis.

Recent increases in common mental disorders (CMDs) among young adults are of great concern although studies of CMDs in young employees are sparse. This study investigated the independent and interacting effects of sector of employment, occupational class and CMDs. Additionally, associations between type of employment branch and CMDs within each sector were examined.

This population-based longitudinal cohort study included 665138 employees, 19-29 years, residing in Sweden in 2009. Employment sector (i.e. private/public) and occupational class (non-manual/manual workers) were measured in 2009. Risk estimates of CMDs, measured as new prescription of antidepressants and/or psychiatric care with a diagnosis of CMDs, between 2010 and 2016, were calculated as hazard ratios (HRs) with 95% confidence intervals (CIs), using Cox multivariable regression analysis.

Public sector employees (whereof 60% manual workers) had an elevated risk for CMDs compared to private sector employees [adjusted HR 1.14 (95% CI 1.12-1.16)]. Within each sector, manual workers were at increased risk of CMDs compared to non-manual workers. There was an interaction between sector of employment and occupational class; manual workers in the public sector had the highest CMD risk [adjusted synergy index 1.51 (95% CI 1.29-1.76)]. The most elevated risk for CMDs was observed in those employed in health and social services and the lowest risk among construction workers.

Sector of employment and occupational class play a role in CMDs in young employees. These findings should be taken into account in the attempts to reduce CMDs in the young working population.

Sector of employment and occupational class play a role in CMDs in young employees. These findings should be taken into account in the attempts to reduce CMDs in the young working population.

This study determined whether the improvements in hypertension management over the last five decades have influenced subjects’ prognosis.

The study considered 5693 eligible subjects seen January 1969 to February 1991 (follow-up until December 2003) or January 1995 to October 2014 (follow-up until July 2016) in an all-grade hypertension reference centre. Missing data or incomplete follow-ups led to exclude 1036 subjects (18%). The outcome was all-cause death. An adjusted modelling of the excess mortality rate assessed subjects’ net survival over five inclusion periods to allow for the increase in life expectancy of the general population during the same periods. The analysis of 4657 records (mean age 47 years; 43.2% women) showed that the proportion of subjects with grade 3 hypertension decreased significantly from 43.3% (1142) to only 6.3% (22) over the five periods and that the net survival improved in men and women regardless of the hypertension grade; i.e. the gain in net survival at 15 years was estimated at 12.3% (95% confidence interval 8.1-22.3). The 15-year restricted mean survival was estimated at 13 years over the first period and 14.8 years over the last period, which is nearly a 2-year gain in life expectancy at 15 years.

Since the 70s and the advent of modern management, the excess mortality of hypertensive subjects (vs. the general population) was markedly reduced. Within a context of trivialization of blood pressure measurement and reluctance to long-term treatments, physicians should consider this advantage and use it to promote blood pressure control.

Since the 70s and the advent of modern management, the excess mortality of hypertensive subjects (vs. the general population) was markedly reduced. Within a context of trivialization of blood pressure measurement and reluctance to long-term treatments, physicians should consider this advantage and use it to promote blood pressure control.

The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population.

Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.