Quiescent satellite cells are myogenic progenitors that enable regeneration of skeletal muscle. One of the early events of satellite cell activation following myotrauma is the induction of the myogenic regulatory factor MyoD, which eventually induces terminal differentiation and muscle function gene expression. The purpose of this study was to elucidate the mechanism by which MyoD is induced during activation of satellite cells in mouse muscle undergoing regeneration. We show that Six1, a transcription factor essential for embryonic myogenesis, also regulates MyoD expression in muscle progenitor cells. Six1 knock-down by RNA interference leads to decreased expression of MyoD in myoblasts. Chromatin immunoprecipitation assays reveal that Six1 binds the Core Enhancer Region of MyoD. Further, transcriptional reporter assays demonstrate that Core Enhancer Region reporter gene activity in myoblasts and in regenerating muscle depends on the expression of Six1 and on Six1 binding sites. Finally, we provide evidence indicating that Six1 is required for the proper chromatin structure at the Core Enhancer Region, as well as for MyoD binding at its own enhancer. Together, our results reveal that MyoD expression in satellite cells depends on Six1, supporting the idea that Six1 plays an important role in adult myogenesis, in addition to its role in embryonic muscle formation.

Highlights d BEACON induces basal levels of DNA breaks and DNA damage response d BEACON induces a basal level of RNA off-target mutations d BEACON induces in vivo base editing with high product purity

There is limited research on the changes of biomechanical characteristics of the lumbar extensor myofascia in elderly patients with chronic low back pain. This study aimed to compare the biomechanical properties of the lumbar extensor myofascia in elderly patients with chronic low back pain and healthy people when resting and to analyze the relationship between the Japanese Orthopedic Association (JOA) score, visual analog scale (VAS) score, Cobb angle, and disease course and the biomechanical characteristics of the lumbar extensor myofascia. This case-control study included 40 elderly patients with chronic low back pain and 40 healthy volunteers. MyotonPRO was used to measure the biomechanical properties of the bilateral lumbar extensor myofascia (at L3/L4 level) in all participants, and the reliability of the MyotonPRO test was measured. Cobb angle was measured from lumbar computed tomography or magnetic resonance imaging data. JOA and VAS scores were used to evaluate lumbar function and pain. We found that muscle tone, stiffness, and elasticity of the left and right lumbar extensor myofascia in patients with chronic low back pain were very reliable among different operators. The average lumbar extensor muscle tone and stiffness were significantly higher in patients with chronic low back pain than those in healthy controls. The average elasticity of the lumbar extensor myofascia of patients with chronic low back pain was significantly lower than that of the healthy controls. The JOA score was negatively correlated, while the VAS score was positively correlated with the mean values of tone, stiffness, and elasticity of the bilateral lumbar extensor myofascia (logarithmic decrement). Disease course had no significant correlation with muscle tone, stiffness, and elasticity of the lumbar extensor myofascia. No significant correlation was found between Cobb angle and muscle tone, stiffness, and elasticity of the lumbar extensor myofascia in either group.

Background Xyloglucan endotransglucosylase/hydrolase genes (XTHs) are a multigene family and play key roles in regulating cell wall extensibility in plant growth and development. Brassica rapa and Brassica oleracea contain XTHs, but detailed identification and characterization of the XTH family in these species, and analysis of their tissue expression profiles, have not previously been carried out. Results In this study, 53 and 38 XTH genes were identified in B. rapa and B. oleracea respectively, which contained some novel members not observed in previous studies. All XTHs of B. rapa, B. oleracea and Arabidopsis thaliana could be classified into three groups, Group I/II, III and the Early diverging group, based on phylogenetic relationships. Gene structures and motif patterns were similar within each group. All XTHs in this study contained two characteristic conserved domains (Glyco_hydro and XET_C). XTHs are located mainly in the cell wall but some are also located in the cytoplasm. Analyses of the mechanisms of gene family expansion revealed that whole-genome triplication (WGT) events and tandem duplication (TD) may have been the major mechanisms accounting for the expansion of the XTH gene family. Interestingly, TD genes all belonged to Group I/II, suggesting that TD was the main reason for the largest number of genes being in these groups. B. oleracea had lost more of the XTH genes, the conserved domain XET_C and the conserved active-site motif EXDXE compared with B. rapa, consistent with asymmetrical evolution between the two Brassica genomes. A majority of XTH genes exhibited different tissue-specific expression patterns based on RNA-seq data analyses. Moreover, there was differential expression of duplicated XTH genes in the two species, indicating that their functional differentiation occurred after B. rapa and B. oleracea diverged from a common ancestor. Conclusions We carried out the first systematic analysis of XTH gene families in B. rapa and B. oleracea. The results of this investigation can be used for reference in further studies on the functions of XTH genes and the evolution of this multigene family.