It remains challenging to predict regulatory variants in particular tissues or cell types due to highly context-specific gene regulation. By connecting large-scale epigenomic profiles to expression quantitative trait loci (eQTLs) in a wide range of human tissues/cell types, we identify critical chromatin features that predict variant regulatory potential. We present cepip, a joint likelihood framework, for estimating a variant’s regulatory probability in a context-dependent manner. Our method exhibits significant GWAS signal enrichment and is superior to existing cell type-specific methods. Furthermore, using phenotypically relevant epigenomes to weight the GWAS single-nucleotide polymorphisms, we improve the statistical power of the gene-based association test.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Previous studies have shown that parental protectiveness is associated with increased pain and disability in Functional Abdominal Pain Disorder (FAPD) but the role that perceived child self-efficacy may play remains unclear. One reason why parents may react protectively towards their child’s pain is that they perceive their child to be unable to cope or function normally while in pain (perceived low self-efficacy). This study sought to examine (a) the association between parent-perceived child pain self-efficacy and child health outcomes (symptom severity and disability); and (b) the role of parental protectiveness as a mediator of this association. Participants were 316 parents of children aged 7–12 years with FAPD. Parents completed measures of perceived child self-efficacy when in pain, their own protective responses to their child’s pain, child gastrointestinal (GI) symptom severity, and child functional disability. Parent-perceived child self-efficacy was inversely associated with parent-reported child GI symptom severity and disability, and parental protectiveness mediated these associations. These results suggest that parents who perceive their child to have low self-efficacy to cope with pain respond more protectively when they believe he/she is in pain, and this, in turn, is associated with higher levels of GI symptoms and disability in their child. This finding suggests that directly addressing parent beliefs about their child’s ability to manage pain should be included as a component of FAPD, and potentially other child treatment interventions.

Objectives: To determine the off-shift sleep strategies of bi-ethnic night-shift nurses, the relationship between these sleep strategies and adaptation to shift work, and identify the participant-level characteristics associated with a given sleep strategy.

Methods: African-American and non-Hispanic White female, night-shift nurses from an academic hospital were recruited to complete a survey on sleep–wake patterns (n = 213). Participants completed the standard shiftwork index and the biological clocks questionnaire to determine sleep strategies and adaptation to night-shift work. In addition, chronotype was determined quantitatively with a modified version of the Munich ChronoType Questionnaire. Most participants worked ~3 consecutive 12-h night-shifts followed by several days off.

Results: Five sleep strategies used on days off were identified: (a) night stay, (b) nap proxy, (c) switch sleeper, (d) no sleep, and (e) incomplete switcher. Nap proxy and no sleep types were associated with poorer adaptation to night-shift work. The switch sleeper and incomplete switcher types were identified as more adaptive strategies that were associated with less sleep disturbance, a later chronotype, and less cardiovascular problems.

Conclusion: Behavioral sleep strategies are related to adaptation to a typical night-shift schedule among hospital nurses. Nurses are crucial to the safety and well-being of their patients. Therefore, adoption of more adaptive sleep strategies may reduce sleep/wake dysregulation in this population, and improve cardiovascular outcomes.

Accumulating data from genome-wide association studies (GWAS) have provided a collection of novel candidate genes associated with complex diseases, such as atherosclerosis. We identified an atherosclerosis-associated single-nucleotide polymorphism (SNP) located in the intron of the long noncoding RNA (lncRNA) LINC00305 by searching the GWAS database. Although the function of LINC00305 is unknown, we found that LINC00305 expression is enriched in atherosclerotic plaques and monocytes. Overexpression of LINC00305 promoted the expression of inflammation-associated genes in THP-1 cells and reduced the expression of contractile markers in co-cultured human aortic smooth muscle cells (HASMCs). We showed that overexpression of LINC00305 activated nuclear factor-kappa beta (NF-κB) and that inhibition of NF-κB abolished LINC00305-mediated activation of cytokine expression. Mechanistically, LINC00305 interacted with lipocalin-1 interacting membrane receptor (LIMR), enhanced the interaction of LIMR and aryl-hydrocarbon receptor repressor (AHRR), and promoted protein expression as well as nuclear localization of AHRR. Moreover, LINC00305 activated NF-κB exclusively in the presence of LIMR and AHRR. In light of these findings, we propose that LINC00305 promotes monocyte inflammation by facilitating LIMR and AHRR cooperation and the AHRR activation, which eventually activates NF-κB, thereby inducing HASMC phenotype switching.

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210–2340 h, (2) treadmill exercise alone from 2210–2340 h, or (3) bright light (2210–2340 h) followed by exercise from 0410–0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect.

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African American adults. African American men and women (n = 1467) completed questionnaires on the social environment, psychosocial factors (stress, depressive symptoms, and racial discrimination), and mental health. Multiple-mediator models were used to assess direct and indirect effects of the social environment on mental health. Low social status in the community (p < .001) and U.S. (p < .001) and low social support (p < .001) were associated with poor mental health. Psychosocial factors significantly jointly mediated the relationship between the social environment and mental health in multiple-mediator models. Low social status and social support were associated with greater perceived stress, depressive symptoms, and perceived racial discrimination, which were associated with poor mental health. Results suggest the relationship between the social environment and mental health is mediated by psychosocial factors and revealed potential mechanisms through which social status and social support influence the mental health of African American men and women. Findings from this study provide insight into the differential effects of stress, depression and discrimination on mental health. Ecological approaches that aim to improve the social environment and psychosocial mediators may enhance health-related quality of life and reduce health disparities in African Americans.