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The telomerase reverse transcriptase (TERT) gene is responsible for telomere maintenance in germline and stem cells, and is re-expressed in 90% of human cancers. CpG methylation in the TERT promoter (TERTp) was correlated with TERT mRNA expression. Furthermore, two hotspot mutations in TERTp, dubbed C228T and C250T, have been revealed to facilitate binding of transcription factor ETS/TCF and subsequent TERT expression. This study aimed to elucidate the combined contribution of epigenetic (promoter methylation and chromatin accessibility) and genetic (promoter mutations) mechanisms in regulating TERT gene expression in healthy skin samples and in melanoma cell lines (n = 61). We unexpectedly observed that the methylation of TERTp was as high in a subset of healthy skin cells, mainly keratinocytes, as in cutaneous melanoma cell lines. In spite of the high promoter methylation fraction in wild-type (WT) samples, TERT mRNA was only expressed in the melanoma cell lines with either high methylation or intermediate methylation in combination with TERT mutations. TERTp methylation was positively correlated with chromatin accessibility and TERT mRNA expression in 8 melanoma cell lines. Cooperation between epigenetic and genetic mechanisms were best observed in heterozygous mutant cell lines as chromosome accessibility preferentially concerned the mutant allele. buy INCB018424 Combined, these results suggest a complex model in which TERT expression requires either a widely open chromatin state in TERTp-WT samples due to high methylation throughout the promoter or a combination of moderate methylation fraction/chromatin accessibility in the presence of the C228T or C250T mutations.BACKGROUND Homocysteine has been known as a risk factor for cardiovascular disease. This study sought to evaluate the influence of homocysteine on the risk of subclinical coronary atherosclerosis in asymptomatic individuals. METHODS We reviewed 3,186 asymptomatic individuals (mean age 53.8 ± 8.0 years, 2,202 men [69.1%]) with no prior history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography (CCTA) and laboratory tests as part of a general health examination. The subjects were stratified into tertiles according to their homocysteine levels. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA. Logistic regression analysis was used to determine the association between homocysteine levels and subclinical coronary atherosclerosis. RESULTS The prevalence of significant coronary artery stenosis, any atherosclerotic, calcified, mixed, and non-calcified plaques increased with homocysteine tertiles (all p less then 0.05). However, after adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios (ORs) for any atherosclerotic plaque (OR 1.06; 95% CI [confidence interval] 0.85-1.32; p = 0.610), calcified plaques (OR 1.17; 95% CI 0.92-1.48; p = 0.199), non-calcified plaques (OR 0.80; 95% CI 0.61-1.04; p = 0.089), and mixed plaques (OR 1.42; 95% CI 0.96-2.11; p = 0.077) between the third and first homocysteine tertiles. In addition, the adjusted OR for significant coronary artery stenosis (OR 0.92; 95% CI 0.63-1.36; p = 0.687) did not differ between the first and third tertiles. CONCLUSIONS In asymptomatic individuals, homocysteine is not associated with an increased risk of subclinical coronary atherosclerosis.With the global-scale loss of biodiversity, current restoration programs have been often required as part of conservation plans for species richness and ecosystem integrity. The restoration of pelagic-oriented cisco (Coregonus artedi) has been an interest of Lake Michigan managers because it may increase the diversity and resilience of the fish assemblages and conserve the integrity of the ecosystems in a changing environment. To inform restoration, we described historical habitat use of cisco by analyzing a unique fishery-independent dataset collected in 1930-1932 by the U.S. Bureau of Fisheries' first research vessel Fulmar and a commercial catch dataset reported by the State of Michigan in the same period, both based on gear fished on the bottom. Our results confirmed that the two major embayments, Green Bay and Grand Traverse Bay, were important habitats for cisco and suggest that the Bays were capable of supporting cisco to complete its entire life cycle in the early 20th century as there was no lack of summer feeding and fall spawning habitats. Seasonally, our results showed that cisco stayed in nearshore waters in spring, migrated to offshore waters in summer, and then migrated back to nearshore waters in fall. The results also suggest that in summer, most ciscoes were in waters with bottom depths of 20-70 m, but the highest cisco density occurred in waters with a bottom depth around 40 m. We highlight the importance of embayment habitats to cisco restoration and the seasonal migration pattern of cisco identified in this study, which suggests that a restored cisco population can diversify the food web by occupying different habitats from the exotic fishes that now dominate the pelagic waters of Lake Michigan.BACKGROUND Women's participation in decision-making in the household is an indicator of women's empowerment. Few studies have compared domestic decision-making power and its effect on postpartum health between immigrant and native-born women. This study aimed to examine the effect of domestic decision-making power and social support during pregnancy on predicting postpartum depressive and physical symptoms among immigrant and native-born mothers in Taiwan. METHODS AND FINDINGS This prospective study recruited 177 marriage-based immigrant mothers and 230 native-born women who were at least twelve weeks pregnant from hospitals, clinics and health centers. Data were collected in the 2nd or 3rd trimester of pregnancy and at 3 months postpartum from March 2013 to March 2015. Postpartum depression and the severity of postpartum physical symptoms were measured using the Edinburgh Postnatal Depression Scale, and a 17-item, 4-point Likert scale, respectively. Linear regression was used to examine the relationship between "domestic decision-making power and social support during pregnancy" and "depressive and physical symptoms at 3 months postpartum.
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