The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy.

Skeletal muscle atrophy occurs in many chronic diseases and disuse conditions. Its severity reduces patient recovery, independence and quality of life. The discovery of two muscle-specific E3 ubiquitin ligases, MAFbx/atrogin-1 and Muscle RING Finger-1 (MuRF1), promoted an expectation of these molecules as targets for therapeutic development. While numerous studies have determined the conditions in which MAFbx/atrogin-1 and MuRF1 mRNA levels are regulated, few studies have investigated their functional role in skeletal muscle. Recently, studies identifying new target substrates for MAFbx/atrogin-1 and MuRF1, outside of their response to the initiation of muscle atrophy, suggest that there is more to these proteins than previously appreciated. This review will highlight our present knowledge of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy, the impact of potential therapeutics and their known regulators and substrates. Finally, we will comment on new approaches that may expand our knowledge of these two molecules in their control of skeletal muscle function.

Function of caspase-14 in trophoblast differentiation.

BACKGROUND: Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. METHODS: Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. RESULTS: Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. CONCLUSION: Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

The Effect of Content Delivery Style on Student Performance in Anatomy.

The development of new technologies and ensuing pedagogical research has led many tertiary institutions to integrate and adopt online learning strategies. The authors of this study have incorporated online learning strategies into existing educational practices of a second year anatomy course, resulting in half of the course content delivered via face-to-face lectures, and half delivered online via tailored video vignettes, with accompanying worksheets and activities. The effect of the content delivery mode on student learning was analyzed by tailoring questions to content presented either face-to-face or online. Four practical tests were conducted across the semester with each consisting of four questions. Within each test, two questions were based on content delivered face-to-face, and two questions were based on content delivered online. Examination multiple choice questions were similarly divided and assessed. Findings indicate that student learning is consistent regardless of the mode of content delivery. However, student viewing habits had a significant impact on learning, with students who viewed videos multiple times achieving higher marks than those less engaged with the online content. Student comments also indicated that content delivery mode was not an influence on learning. Therefore student engagement, rather than the mode of content delivery, is a determinant of student learning and performance in human anatomy. Anat Sci Educ. © 2018 American Association of Anatomists.