Ebf factors and MyoD cooperate to regulate muscle relaxation via Atp2a1

Jin, Saihong et al.Myogenic regulatory factors such as MyoD and Myf5 lie at the core of vertebrate muscle differentiation. However, E-boxes, the cognate binding sites for these transcription factors, are not restricted to the promoters/enhancers of muscle cell-specific genes. Thus, the specificity in myogenic transcription is poorly defined. Here we describe the transcription factor Ebf3 as a new determinant of muscle cell-specific transcription. In the absence of Ebf3 the lung does not unfold at birth, resulting in respiratory failure and perinatal death. This is due to a hypercontractile diaphragm with impaired Ca2+ efflux-related muscle functions. Expression of the Ca2+ pump Serca1 (Atp2a1) is downregulated in the absence of Ebf3, and its transgenic expression rescues this phenotype. Ebf3 binds directly to the promoter of Atp2a1 and synergises with MyoD in the induction of Atp2a1. In skeletal muscle, the homologous family member Ebf1 is strongly expressed and together with MyoD induces Atp2a1. Thus, Ebf3 is a new regulator of terminal muscle differentiation in the diaphragm, and Ebf factors cooperate with MyoD in the induction of muscle-specific genes. © 2014 Macmillan Publishers Limited.This work was supported by grants from the German Research Foundation (DFG, TRR54; FOR1586; FOR2033) and by a stipend of the Max Planck SocietyPeer Reviewe

Climate change impacts on human health over Europe through its effect on air quality

Abstract This review examines the current literature on the effects of future emissions and climate change on particulate matter (PM) and O3 air quality and on the consequent health impacts, with a focus on Europe. There is considerable literature on the effects of climate change on O3 but fewer studies on the effects of climate change on PM concentrations. Under the latest Intergovernmental Panel on Climate Change (IPCC) 5th assessment report (AR5) Representative Concentration Pathways (RCPs), background O3 entering Europe is expected to decrease under most scenarios due to higher water vapour concentrations in a warmer climate. However, under the extreme pathway RCP8.5 higher (more than double) methane (CH4) abundances lead to increases in background O3 that offset the O3 decrease due to climate change especially for the 2100 period. Regionally, in polluted areas with high levels of nitrogen oxides (NOx), elevated surface temperatures and humidities yield increases in surface O3 – termed the O3 climate penalty – especially in southern Europe. The O3 response is larger for metrics that represent the higher end of the O3 distribution, such as daily maximum O3. Future changes in PM concentrations due to climate change are much less certain, although several recent studies also suggest a PM climate penalty due to high temperatures and humidity and reduced precipitation in northern mid-latitude land regions in 2100. A larger number of studies have examined both future climate and emissions changes under the RCP scenarios. Under these pathways the impact of emission changes on air quality out to the 2050s will be larger than that due to climate change, because of large reductions in emissions of O3 and PM pollutant precursor emissions and the more limited climate change response itself. Climate change will also affect climate extreme events such as heatwaves. Air pollution episodes are associated with stagnation events and sometimes heat waves. Air quality during the 2003 heatwave over Europe has been examined in numerous studies and mechanisms for enhancing O3 have been identified. There are few studies on health effects associated with climate change impacts alone on air quality, but these report higher O3-related health burdens in polluted populated regions and greater PM2.5 health burdens in these emission regions. Studies that examine the combined impacts of climate change and anthropogenic emissions change under the RCP scenarios report reductions in global and European premature O3-respiratory related and PM mortalities arising from the large decreases in precursor emissions. Under RCP 8.5 the large increase in CH4 leads to global and European excess O3-respiratory related mortalities in 2100. For future health effects, besides uncertainty in future O3 and particularly PM concentrations, there is also uncertainty in risk estimates such as effect modification by temperature on pollutant-response relationships and potential future adaptation that would alter exposure risk

Linkage to Care and Treatment for TB and HIV among People Newly Diagnosed with TB or HIV-Associated TB at a Large, Inner City South African Hospital

OBJECTIVE: To assess the outcomes of linkage to TB and HIV care and identify risk factors for poor referral outcomes. DESIGN: Cohort study of TB patients diagnosed at an urban hospital. METHODS: Linkage to care was determined by review of clinic files, national death register, and telephone contact, and classified as linked to care, delayed linkage to care (>7 days for TB treatment, >30 days for HIV care), or failed linkage to care. We performed log-binomial regression to identify patient and referral characteristics associated with poor referral outcomes. RESULTS: Among 593 TB patients, 23% failed linkage to TB treatment and 30.3% of the 77.0% who linked to care arrived late. Among 486 (86.9%) HIV-infected TB patients, 38.3% failed linkage to HIV care, and 32% of the 61.7% who linked to care presented late. One in six HIV-infected patients failed linkage to both TB and HIV care. Only 20.2% of HIV-infected patients were referred to a single clinic for integrated care. A referral letter was present in 90.3%, but only 23.7% included HIV status and 18.8% CD4 cell count. Lack of education (RR 1.85) and low CD4 count (CD4≤50 vs. >250cells/mm(3); RR 1.66) were associated with failed linkage to TB care. Risk factors for failed linkage to HIV care were antiretroviral-naïve status (RR 1.29), and absence of referral letter with HIV or CD4 cell count (RR1.23). CONCLUSIONS: Linkage to TB/HIV care should be strengthened by communication of HIV and CD4 results, ART initiation during hospitalization and TB/HIV integration at primary care