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.

During embryonic development, progenitor cells arising from the somitic mesoderm commit to a program of differentiation that facilitates the formation of skeletal muscle fibers (termed myogenesis). Under the control of a number of extracellular cues, these myogenic precursors adhere to an orchestrated process of mobilization, proliferation, differentiation, and fusion to create the multi-nucleated myotubes that ultimately become mature fibers (1-3). Many of the most important early changes in gene expression that direct the muscle cell lineage are driven by a family of basic helix-loop-helix transcription factors that includes MyoD, myogenin, MRF4, and Myf5, which are therefore commonly referred to as the muscle regulatory factors (MRFs) 2 (4 -6).TGF-␤ is well characterized as a potent inhibitor of muscle cell differentiation that acts by repressing the transcriptional activity of MRFs (7-9). Interaction between extracellular TGF-␤ and its membrane-bound receptor complex engages a cascade of intracellular signal transduction that promotes nuclear retention of Smad proteins 2 and 3 in complex with Smad4, which subsequently activates or represses hundreds of TGF-␤ target genes (10). Of particular relevance to skeletal muscle cell differentiation, the TGF-␤ signaling protein Smad3 has been shown to physically interact with MRFs in a manner that can inhibit differentiation (9). microRNAs (or miRs) are single-stranded 21-22-nucleotide noncoding RNAs that are capable of controlling gene expression at a post-transcriptional level by stalling the translation of the cognate mRNA or promoting its degradation in a process referred to as RNA interference (RNAi). Here, individual miRs that have been loaded into a specialized collection of interacting proteins referred to as the RNA-induced silencing complex identify and bind to highly specific sequences featuring within exons or the 3Ј-untranslated regions of target mRNAs. The degree of pairing complementarity between a microRNA and its target (as well as target location in the transcript) determine whether translation is subsequently repressed or the transcript is degraded (11,12). In skeletal muscle, specific miRs are increasingly being implicated as key regulators of differentiation, because of their predicted selectivity for genes that are involved in facilitating the myogenic program. Chief among these microRNAs are the so-called "myomiRs," or muscle-enriched microRNAs (including miR-1/206, -133a, and -133b) that are themselves transcribed as targets of MRF activity. As an example, increased miR-206 levels promote myogenic differentiation in vitro (13,14) and in vivo (15, 16), whereas inhibiting miR-206 appears capable of delaying or even preventing myogenic differentiation. Ongoing examination is establishing that additional miRs that are expressed in a variety of cell types including but not exclusive to skeletal muscle may also influence the events of differentiation. For instance, the miR-29 family regulates myogenesis by targeting proteins within the NF-B-YY1 sig...

Benefits of collaborative testing have been identified in many disciplines. This study sought to determine whether collaborative practical tests encouraged active learning of anatomy. A gross anatomy course included a collaborative component in four practical tests. Two hundred and seven students initially completed the test as individuals and then worked as a team to complete the same test again immediately afterwards. The relationship between mean individual, team, and difference (between team and individual) test scores to overall performance on the final examination (representing overall learning in the course) was examined using regression analysis. The overall mark in the course increased by 9% with a decreased failure rate. There was a strong relationship between individual score and final examination mark (P < 0.001) but no relationship for team score (P = 0.095). A longitudinal analysis showed that the test difference scores increased after Test 1 which may be indicative of social loafing and this was confirmed by a significant negative relationship between difference score on Test 4 (indicating a weaker student) and final examination mark (P < 0.001). It appeared that for this cohort, there was little peer-to-peer learning occurring during the collaborative testing and that weaker students gained the benefit from team marks without significant active learning taking place. This negative outcome may be due to insufficient encouragement of the active learning strategies that were expected to occur during the collaborative testing process. An improved understanding of the efficacy of collaborative assessment could be achieved through the inclusion of questionnaire based data to allow a better interpretation of learning outcomes. Anat Sci Educ 9: 231-237. © 2015 American Association of Anatomists.

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.

The human placenta is responsible for the exchange of nutrients, gas and wastes through the trophoblast maternal-fetal barrier, which is formed by the fusion of villous cytotrophoblasts to form the continuous multinucleated syncytiotrophoblast separating the maternal and fetal circulations. Caspase-14 is a seemingly non-apoptotic caspase involved in keratinocyte differentiation and cornification. It is proposed that caspase-14 has a conserved role in cellular differentiation and a role in differentiation and fusion in the trophoblast. The human choriocarcinoma BeWo cell line was treated with staurosporine and forskolin to induce apoptosis and differentiation respectively. Staurosporine initiated apoptosis within 3 h of treatment, while apoptosis was completed following 6 h treatment. Caspase-14 gene and protein expression was unchanged throughout this process. During BeWo differentiation, caspase-14 mRNA was elevated after 48 h forskolin treatment, while its protein was increased after 24 h. Therefore, caspase-14 is up-regulated during trophoblast differentiation, as represented by the BeWo cell line. Moreover, caspase-14 may interact with other signalling molecules to facilitate differentiation. This new data confirms the potential for the BeWo cell line in the functional dissection of this unusual caspase and its prospective role in trophoblast differentiation.