Extracellular vesicle miR-206 improves chronic binge alcohol mediated decreased myoblast differentiation in SIV-infected female macaques.

Alcohol misuse in people with HIV (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells, or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The current study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreased myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 months. Myotube and myotube derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 (HDAC4) and paired box 7 (PAX7) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation.

Genetic variation among populations of, and evidence of deep divergence within, the Rio Grande Chirping Frog, Eleutherodactylus campi (Anura: Eleutherodactylidae).

Herein we report the first molecular assessment of intra-species genetic variation and interrelationships within the Rio Grande Chirping frog, Eleutherodactylus campi. We analyzed 548 base pairs of 16S rRNA gene for 71 ingroup individuals belonging to the genus Eleutherodactylus (including 42 E. campi sampled from 15 localities in the United States and Mexico) and four outgroup samples. By unveiling two highly divergent and geographically structured clades within E. campi this study provides a novel phylogenetic placement of E. campi populations north and south of the Rio Grande Valley as sister groups to each other. The observed level of genetic divergence between these two clades (5.8%) is, on average, comparable to or greater than the levels of divergence found between several currently valid amphibian species pairs. Estimates of Time to Most Common Ancestor (TMRCA) indicate that the phylogeographic split between the two E. campi clades may have occurred 7.6 MYA (i.e., late Miocene), consistent with the geologic history of southwestern North America. The study also confirms that south Texas served as the source population for populations of E. campi in its introduced range (i.e., Alabama, Louisiana, and Texas). Overall, this molecular study indicates that E. campi consists of two deeply divergent lineages corresponding to its populations north and south of Rio Grande Valley. These results suggest that the recovered lineages may represent independent species and thereby highlight the need for further research to clarify their status.