Developmental nicotine exposure causes persistent changes in cortical neuron morphology and in behavior. We used microarray screening to identify master transcriptional or epigenetic regulators mediating these effects of nicotine and discovered increases in Ash2l, a component of a histone methyltransferase complex. We therefore examined genome-wide changes in H3K4 tri-methylation, a mark induced by the Ash2l complex associated with increased gene transcription. A significant number of regulated promoter sites were involved in synapse maintenance. We found that Mef2c interacts with Ash2l and mediates changes in H3K4 tri-methylation. Knockdown of Ash2l or Mef2c abolishes nicotine-mediated alterations of dendritic complexity in vitro and in vivo, and attenuates nicotine-dependent changes in passive avoidance behavior. In contrast, overexpression mimics nicotine-mediated alterations of neuronal structure and passive avoidance behavior. These studies identify Ash2l as a novel target induced by nicotinic stimulation that couples developmental nicotine exposure to changes in brain epigenetic marks, neuronal structure and behavior.
While exposure to nicotine during developmental periods can significantly affect brain development, studies examining the association between maternal smoking and autism spectrum disorder (ASD) in offspring have produced conflicting findings, and prior meta-analyses have found no significant association. Our meta-analysis used a novel approach of investigating population-level smoking metrics as moderators. The main meta-analysis, with 22 observational studies comprising 795,632 cases and 1,829,256 control participants, used a random-effects model to find no significant association between maternal smoking during pregnancy and ASD in offspring (pooled odds ratio (OR) = 1.16, 95% CI: 0.97–1.40). However, meta-regression analyses with moderators were significant when we matched pooled ORs with adult male smoking prevalence (z = 2.55, p = 0.01) in each country, using World Health Organization data. Our study shows that using population-level smoking metrics uncovers significant relationships between maternal smoking and ASD risk. Correlational analyses show that male smoking prevalence approximates secondhand smoke exposure. While we cannot exclude the possibility that our findings reflect the role of paternal or postnatal nicotine exposure, as opposed to maternal or in utero nicotine exposure, this study underlines the importance of investigating paternal and secondhand smoking in addition to maternal smoking in ASD.
The rise of sophisticated tools for tracking audiences online has begun to change the way media producers think about media audiences. This study examines this phenomenon in journalism, building on a revised theoretical model that accounts for greater audience engagement in the gatekeeping process. Research suggests that news editors, after long resisting or ignoring audience preferences, are becoming increasingly aware of and adaptive to consumer tastes as manifest via metrics. However, research also finds a gap in the news preferences of editors and audiences. This study asks: Who influences whom more in this disparity? Through longitudinal secondary data analysis of three U.S. online newspapers, and using structural equation modeling, this study finds that (a) audience clicks affect subsequent news placement, based on time-lagged analysis; (b) such influence intensifies during the course of the day; (c) there is no overall lagged effect of news placement on audience clicks; and (d) the lagged effect of audience clicks on news placement is stronger than the inverse. Implications of these findings and suggestions for future research are discussed.
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