Enhancer RNAs are necessary and sufficient for activity-dependent neuronal gene transcription

Enhancer elements in DNA regulate gene expression programs important for neuronal fate and function, and are increasingly implicated in brain disease states. Enhancers undergo bidirectional transcription to generate non-coding enhancer RNAs (eRNAs), but the function of eRNAs in neuronal systems remains controversial. Here, we performed genome-wide characterization of transcribed enhancers from rat cortical neurons, revealing elevated sequence conservation, enriched localization near genes involved in neuronal or synaptic function, and correlated activity-dependent regulation of putative eRNA-mRNA pairs. Functional validation using a CRISPR-dCas9 fusion system to drive eRNA synthesis from enhancers produced corresponding increases in mRNA at linked genes. Focusing on eRNAs arising from enhancers at the Fos gene locus, we report that eRNA and mRNA correlate on a single-cell level, that CRISPR-targeted eRNA delivery to an enhancer is sufficient for mRNA induction, and that eRNA knockdown decreases mRNA and alters neuronal physiology. These results suggest that eRNAs regulate gene expression and neuronal function

Health Status Outcomes in Older Adults Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention

Background Although chronic total occlusions (CTOs) are common in older adults, they are less likely to be offered CTO percutaneous coronary intervention for angina relief than younger adults. The health status impact of CTO percutaneous coronary intervention in adults aged ≥75 years has not been studied. We sought to compare technical success rates and angina‐related health status outcomes at 12 months between adults aged ≥75 and <75 years in the OPEN‐CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion) registry. Methods and Results Angina‐related health status was assessed with the Seattle Angina Questionnaire (score range 0–100, higher scores denote less angina). Technical success rates were compared using hierarchical modified Poisson regression, and 12‐month health status was compared using hierarchical multivariable linear regression between adults aged ≥75 and <75 years. Among 1000 participants, 19.8% were ≥75 years with a mean age of 79.5±4.1 years. Age ≥75 years was associated with a lower likelihood of technical success (adjusted risk ratio=0.92 [95% CI, 0.86–0.99; P=0.02]) and numerically higher rates of in‐hospital major adverse cardiovascular events (9.1% versus 5.9%, P=0.10). There was no difference in Seattle Angina Questionnaire Summary Score at 12 months between adults aged ≥75 and <75 years (adjusted difference=0.9 [95% CI, −1.4 to 3.1; P=0.44]). Conclusions Despite modestly lower success rates and higher complication rates, adults aged ≥75 years experienced angina‐related health status benefits after CTO‐percutaneous coronary intervention that were similar in magnitude to adults aged <75 years. CTO percutaneous coronary intervention should not be withheld based on age alone in otherwise appropriate candidates

Chapter 2 “Watching What I’m Doing, Watching How I’m doing It”: Exploring the Everyday Experiences of Surveillance and Silenced Voices Among Marginalized Mothers in Welsh Low-Income Locales

Motherhood and mothering are conceived in relation to classed hierarchies through which those in living in poverty become characterised by ‘otherhood’ and ‘othering’. This positioning leaves them vulnerable to overt and indirect forms of criticism, surveillance and policing from family, friends, professionals and strangers; against a background of demonisation of particular types of mothers and mothering practices in the wider mediascape. This paper draws on three studies, involving 28 participants, which explored their journeys into the space of parenthood and their everyday experiences. The participants all resided in low-income locales. Many participants had resided in homeless hostels and mother and baby units before being placed in local authority housing or low grade rented accommodation. The studies all employed forms of visual ethnography including photo-elicitation, timelines, emotion stickers, collage and sandboxing. Participants discussed different forms of surveillance where other people were characterised as ‘watching what I’m doing, watching how I’m doing it’. These forms of watching ranged from the structured policing encountered in mother-and-baby units to more informal comments from passers-by or passengers on a bus journey; and an awareness of how mothers in state housing are depicted in the media. These interactions were sometimes met with resistance, at other times they were simply another incident that participants negotiated in a growing tapestry of disrespect and devaluation. This chapter argues that these discourses demonise and alienate mothers living on the margins, making already difficult journeys a constant struggle in the moral maze of contemporary motherhood and its accompanying conceptualisations of ‘otherhood’