Ovarian hormones induce de novo DNA methyltransferase expression in the Siberian hamster suprachiasmatic nucleus

Experiments investigated neuroanatomically localized changes in de novo DNA methyltransferase expression in the female Siberian hamster (Phodopus sungorus). The objectives were to identify the neuroendocrine substrates that exhibit rhythmic Dnmt3a and Dnmt3b expression across the oestrous cycle and examine the role of ovarian steroids. Hypothalamic Dnmt3a expression was observed to significantly increase during the transition from proestrous to oestrous. A single bolus injection of diethylstilbestrol (DES) and progesterone was sufficient to increase Dnmt3a cell numbers and Dnmt3b immunoreactive intensity in the suprachiasmatic nucleus (SCN). In vitro analyses using an embryonic rodent cell line revealed that DES was sufficient to induce Dnmt3b expression. Upregulating DNA methylation in vitro reduced expression of vasoactive intestinal polypeptide, Vip, and the circadian clock gene, Bmal1. Together, these data indicate that ovarian steroids drive de novo DNA methyltransferase expression in the mammalian suprachiasmatic nucleus and increased methylation may regulate genes involved in the circadian timing of oestrous: Vip and Bmal1. Overall, epigenetically mediated neuroendocrine reproductive events may reflect an evolutionarily ancient process involved in the timing of female fertility

The afterglow and kilonova of the short GRB 160821B

GRB 160821B is a short duration gamma-ray burst (GRB) detected and localized by the Neil Gehrels Swift Observatory in the outskirts of a spiral galaxy at z=0.1613, at a projected physical offset of 16 kpc from the galaxy's center. We present X-ray, optical/nIR and radio observations of its counterpart and model them with two distinct components of emission: a standard afterglow, arising from the interaction of the relativistic jet with the surrounding medium, and a kilonova, powered by the radioactive decay of the sub-relativistic ejecta. Broadband modeling of the afterglow data reveals a weak reverse shock propagating backward into the jet, and a likely jet-break at 3.5 d. This is consistent with a structured jet seen slightly off-axis while expanding into a low-density medium. Analysis of the kilonova properties suggests a rapid evolution toward red colors, similar to AT2017gfo, and a low nIR luminosity, possibly due to the presence of a long-lived neutron star. The global properties of the environment, the inferred low mass (M_ej < 0.006 Msun) and velocities (v > 0.05 c) of lanthanide-rich ejecta are consistent with a binary neutron star merger progenitor.Comment: 14 pages, 6 figures, MNRAS, in press. Moderate revision, added Figure 5 and X-ray data to Table

Estrategia invasiva de rutina en el síndrome coronario agudo sin elevación del segmento ST con disfunción renal. Resultados del registro ARIAM-SEMICYUC

Objetivo: Evaluar la utilización y efectividad de la estrategia invasiva de rutina (EIR) en pacientes con síndrome coronario agudo sin elevación de ST con disfunción renal en el mundo real. Métodos: Estudio de cohortes retrospectivo basado en el registro ARIAM-SEMICYUC (años 2011- 2014). Se consideró que había disfunción renal cuando el GFR (Cockroft-Gault) era menor de 60 ml/min (disfunción moderada) o de 30 ml/min (disfunción grave). Se excluyeron los pacientes en los que la coronariografía precoz (< 72 h) se debió a shock cardiogénico o isquemia recurrente. El desenlace primario fue la mortalidad hospitalaria. El control del confounding se realizó mediante un análisis de propensión. Resultados: Se analizan 4.279 pacientes, de los cuales un 26% tenía disfunción renal moderada y un 5% disfunción grave. Los pacientes con disfunción renal presentaron una mayor gravedad y comorbilidad, una mayor mortalidad hospitalaria (8,6 frente a 1,8%) y una menor utilización de la EIR (40 frente a 52%). Las OR ajustadas mediante emparejamiento para pacientes sin/con disfunción renal fueron de 0,38 (intervalo de confianza al 95% [IC95%] de 0,17 a 0,81) y 0,52 (IC95% de 0,32 a 0,87), respectivamente (p de interacción 0,4779). El impacto de la EIR (diferencia de riesgos ajustada) fue mayor en el grupo con disfunción renal (−5,1%, IC95% entre −8,1 y −2,1, frente a −1,6%, IC95% entre −2,6 y −0,6, p de interacción = 0,0335). Tampoco se detectó interacción significativa respecto a los demás enlaces considerados (mortalidad en UCI o a los 30 días, riesgo combinado de muerte o infarto, fracaso renal agudo o hemorragias moderadas/graves). Conclusiones: Los resultados evidencian que la efectividad de la EIR es similar en pacientes con función renal normal o reducida y alertan sobre una infrautilización de esta estrategia en estos últimos.Objective: To evaluate the use and effectiveness of a routine invasive strategy (RIS) in patients with acute coronary syndrome without persistent ST-segment elevation with renal dysfunction in the real world scenario. Methods: A retrospective cohort study based on the ARIAM-SEMICYUC Registry (2011-2014) was carried out. Renal dysfunction was defined as GFR (Cockroft-Gault)<60ml/min (moderate dysfunction) or<30ml/min (severe dysfunction). Patients in which early angiography (<72h) was performed due to cardiogenic shock or recurrent myocardial ischemia were excluded. The primary endpoint was hospital mortality. Confounding factors were controlled using propensity score analysis. Results: A total of 4,279 patients were analyzed, of which 26% had moderate renal dysfunction and 5% severe dysfunction. Patients with renal dysfunction had greater severity and comorbidity, higher hospital mortality (8.6 vs. 1.8%), and lesser use of the RIS (40 vs. 52%). The adjusted OR for mortality in patients without/with renal dysfunction were 0.38 (95% confidence interval [95%CI] 0.17 to 0.81) and 0.52 (95%CI 0.32 to 0.87), respectively (interaction P-value=.4779). The impact (adjusted risk difference) of RIS was higher in the group with renal dysfunction (-5.1%, 95%CI -8.1 to -2.1 vs. -1.6%, 95%CI -2.6 to -0.6; interaction P-value=.0335). No significant interaction was detected for the other endpoints considered (ICU mortality, 30-day mortality, myocardial infarction, acute renal failure or moderate/severe bleeding).Conclusions: The results suggest that the effectiveness of IRS is similar in patients with normal or abnormal renal function, and alert to the under-utilization of this strategy in such patients

Role of Mitochondrial Complex IV in Age-Dependent Obesity

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion