Sex-specific DNA methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes.

Sex-linked differences in mitochondrial ATP production, enzyme activities, and reactive oxygen species generation have been reported in multiple tissue and cell types. While the effects of reproductive hormones underlie many of these differences, regulation of sexually dimorphic mitochondrial function has not been fully characterized. We hypothesized that sex-specific DNA methylation contributes to sex-specific expression of nuclear genes that influence mitochondrial function. Herein, we analysed DNA methylation data specifically focused on nuclear-encoded mitochondrial genes in 191 males and 190 females. We found 596 differentially methylated sites (DMSs) (FDR p < 0.05), corresponding to 324 genes, with at least a 1% difference in methylation between sexes. To investigate the potential functional significance, we utilized gene expression microarray data. Of the 324 genes containing DMSs, 17 showed differences in gene expression by sex. Particularly striking was that ATP5G2, encoding subunit C of ATP synthase, contains seven DMSs and exhibits a sex difference in expression (p = 0.04). Finally, we also found that alterations in DNA methylation associated with in utero tobacco smoke exposure were sex-specific in these nuclear-encoded mitochondrial genes. Interestingly, the level of sex differences in DNA methylation at nuclear-encoded mitochondrial genes and the level of methylation changes associated with smoke exposure were less prominent than that of other genes. This suggests more conservative regulation of DNA methylation at these nuclear-encoded mitochondrial genes as compared to others. Overall, our findings suggest that sex-specific DNA methylation may help establish sex differences in expression and function and that sex-specific alterations in DNA methylation in response to exposures could contribute to sex-variable toxicological responses.

Student Perceptions of a University Medical Amnesty Policy Are Impacted by Race and Racism: A Qualitative Study.

BACKGROUND: Alcohol consumption on college and university campuses is a public health concern. Some universities have instituted medical amnesty policies (MAPs) to encourage calling first responders to the scene of an alcohol-related emergency. This study describes perceptions of a university MAP and the perceived risks of calling first responders among a sample of undergraduate students at a mid-sized, private, residential university. Methods: This is an exploratory, peer-led study, in which student-researchers worked under faculty supervision to devise the aims of the study, recruit and conduct qualitative interviews with participants, analyze data, and organize major findings. Results: Participants in this convenience sample (N = 42) were majority female (n = 33, 78.67%) and white (n = 35, 83.3%). White students often reported risking disciplinary consequences (i.e. suspension) if found in violation of university alcohol policy. White students who were familiar with the MAP praised it as beneficial in improving student safety. Students of color (especially Black students) reported concerns for their safety in the presence of first responders (especially police officers). Awareness of the MAP among students of color was very low, and many reported low levels of institutional trust, suggesting the protections conferred by the MAP should be taken "with a grain of salt." Conclusions: MAPs may alleviate concern about some perceived risks of calling first responders, but that benefit may not be experienced equitably among students of color. More research is needed to understand the complex relationship between alcohol policies, alcohol-related injuries, policing, and race on college and university campuses.