While significant effort has been dedicated to the characterization of epigenetic changes associated with pre-natal differentiation relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully functional differentiated cell types with limited lifespans arise. Here we sought to address this gap by generating epigenomic and transcriptional profiles from primary human breast cell types isolated from disease-free human subjects. From these data we define a comprehensive human breast transcriptional network, including a set of myoepithelial- and luminal epithelial- specific intronic retention events. Intersection of epigenetic states with RNA expression from distinct breast epithelium lineages demonstrates that mCpG provides a stable record of exonic and intronic usage whereas H3K36me3 is dynamic. We find a striking asymmetry in epigenomic reprogramming between luminal and myoepithelial cell types, with the genomes of luminal cells harboring more than twice the number of hypomethylated enhancer elements compared to myoepithelial cells.

Foodborne illness due to consumption of products contaminated with Salmonella Typhimurium (S.T.), Listeria monocytogenes (L.m.), and Escherichia coli O157:H7 (E.c.) results in many deaths and significant economic losses each year. In this study, acetic (AA), citric acid (CA), lactic acid (LA), malic acid (MA), and tartaric acid (TA) and grape seed (GS), green tea (GT), bitter melon seed (BMS), rasum, and fenugreek (FG) extracts were investigated as inhibitors against S.T., L.m., and E.c. in both broth-culture and meat systems. Brain Heart Infusion solutions containing 18.7, 37.5, and 75.0 mM organic acids and 5, 10, 20, and 40 mg/mL extracts were challenged with approximately log 6 CFU/mL S.T., L.m., and E.c. A pH-adjusted control was included to determine pH effect on exhibited antibacterial activity. For the meat system, 1 to 2 g chicken breast pieces were vacuum-infused with CA/MA/TA acid at 75 and 150 mM and GS and GT at 3000, 6000, and 9000 ppm in a partial factorial arrangement. GT and GS showed considerable activity in broth-culture. All organic acids were effective in broth-culture at 75 mM after 24 h (P < 0.05). CA and TA were effective at 37.5 mM. CA/MA/TA at 150.0 mM were the most effective in the meat system, reducing E.c., L.m. and S.T. by >5, >2, and 4-6 log CFU/g, respectively, although all organic acids showed some antibacterial activity at 75.0 and 150.0 mM. These findings demonstrate the effectiveness of organic acids and plant extracts in the control of S.T., L.m., and E.c. O157:H7.

Compensatory mutations improve fitness in genotypes that contain deleterious mutations but have no beneficial effects otherwise. As such, compensatory mutations represent a very specific form of epistasis. We show that intragenic compensatory mutations occur non-randomly over gene sequence. Compensatory mutations are more likely to appear at some sites than others. Moreover, the sites of compensatory mutations are more likely than expected by chance to be near the site of the original deleterious mutation. Furthermore, compensatory mutations tend to occur more commonly in certain regions of the protein even when controlling for clustering around the site of the deleterious mutation. These results suggest that compensatory evolution at the protein level is partially predictable and may be convergent.

No abstract