Like the liver or other peripheral organs, two regions of the adult brain possess the ability of selfrenewal through a process called neurogenesis. This raises tremendous hope for repairing the damaged brain and has stimulated research on identifying signals controlling neurogenesis. Neurogenesis involves several stages from fate determination to synaptic integration via proliferation, migration, and maturation. While fate determination primarily depends on a genetic signature, other stages are controlled by the interplay between genes and micro-environmental signals. Here, we propose that neurotransmitters are master regulators of the different stages of neurogenesis. In favor of this idea, a description of selective neurotransmitter signaling and their functions in the largest neurogenic zone, the subventricular zone (SVZ), is provided. In particular, we emphasize the interactions between neuroblasts and astrocyte-like cells that release gammaaminobutyric acid (GABA) and glutamate, respectively. However, we also raise several limitations to our knowledge on neurotransmitters in neurogenesis. The function of neurotransmitters in vivo remains largely unexplored. Neurotransmitter signaling has been viewed as uniform which dramatically contrasts with the cellular and molecular mosaic nature of the SVZ. How neurotransmitters are integrated with other well-conserved molecules, such as sonic hedgehog, is poorly understood. In an effort to reconcile these differences, we discuss how specificity of neurotransmitter functions can be provided through their multitude of receptors and intracellular pathways in different cell types, and their possible interactions with sonic hedgehog.

Sex differences in the development of the normal heart and the prevalence of cardiomyopathies have been reported. The molecular basis of these differences remains unclear. Sex differences in the human heart might be related to patterns of gene expression. Recent studies have shown that sex specific differences in gene expression in tissues including the brain, kidney, skeletal muscle, and liver. Similar data is limited for the heart. Herein we address this issue by analyzing donor and post-mortem adult human heart samples originating from 46 control individuals to study whole-genome gene expression in the human left ventricle. Using data from the genotype tissue expression (GTEx) project, we compared the transcriptome expression profiles of male and female hearts. We found that genes located on sex chromosomes were the most abundant ones among the sexually dimorphic genes. The majority of differentially expressed autosomal genes were those involved in the regulation of inflammation, which has been found to be an important contributor to left ventricular remodeling. Specifically, genes on autosomal chromosomes encoding chemokines with inflammatory functions (e.g. CCL4, CX3CL1, TNFAIP3) and a gene that regulates adhesion of immune cells to the endothelium (e.g., VCAM1) were identified with sex-specific expression levels. This study underlines the relevance of sex as an important modifier of cardiac gene expression. These results have important implications in the understanding of the differences in the physiology of the male and female heart transcriptome and how they may lead to different sex specific difference in human cardiac health and its control.

Objectives To evaluate whether radiation exposure from cardiac computed tomographic angiography is associated with DNA damage and whether damage leads to programmed cell death and activation of genes involved in apoptosis and DNA repair. Background Exposure to radiation from medical imaging has become a public health concern, but whether it causes significant cell damage remains unclear. Methods We conducted a prospective cohort study in 67 patients undergoing cardiac computed tomographic angiography (CTA) between January 2012 and December 2013 in two US medical centers. Median blood radiation exposure was estimated using phantom dosimetry. Biomarkers of DNA damage and apoptosis were measured by flow cytometry, whole genome sequencing, and single cell polymerase chain reaction. Results The median DLP was 1535.3 mGy·cm (969.7 – 2674.0 mGy·cm). The median radiation dose to the blood was 29.8 milliSieverts (18.8 – 48.8 mSv). Median DNA damage increased 3.39% (1.29 – 8.04%, P<0.0001) post-radiation. Median apoptosis increased 3.1-fold (1.4 – 5.1-fold, P<0.0001) post-radiation. Whole genome sequencing revealed changes in the expression of 39 transcription factors involved in the regulation of apoptosis, cell cycle, and DNA repair. Genes involved in mediating apoptosis and DNA repair were significantly changed post-radiation, including DDB2 [1.9-fold (1.5 – 3.0-fold), P<0.001], XRCC4 [3.0-fold (1.1 – 5.4-fold), P=0.005], and BAX [1.6-fold (0.9 – 2.6-fold), P<0.001]. Exposure to radiation was associated with DNA damage [OR: 1.8 (1.2 – 2.6), P=0.003]. DNA damage was associated with apoptosis [OR: 1.9 (1.2 – 5.1), P<0.0001] and gene activation [OR: 2.8 (1.2 – 6.2), P=0.002]. Conclusions Patients exposed to radiation from cardiac CTA had evidence of DNA damage, which was associated with programmed cell death and activation of genes involved in apoptosis and DNA repair.