The Role of MMP9 in Satellite Cell Activation After Increased Activity

The unique adaptive ability of skeletal muscle to meet functional demands is exemplified in its response to exercise. Though little is known about the molecular mechanisms that regulate this plasticity, the extracellular matrix (ECM) is believed to play a large role. The basal lamina is a specialized layer of ECM that lies in direct contact with the cell membrane of muscle fibers and facilitates environment-to-cell interactions. Matrix metalloproteinase-9 (MMP-9) is an enzyme in the basal lamina that regulates much of these adaptive processes. During exercise, the regenerative process of damaged tissue requires the activation of muscle-specific stem cells known as satellite cells. Satellite cell activity has been proposed to be activated by MMP-9; However, there are no studies that look at this interaction. Thus the overall goal of the present proposal is to 1) determine the effects of MMP-9 on muscle hypertrophy via satellite cell activation and 2) assess whether hypertrophy of the plantaris muscle observed after functional overload (FO) is due to the increased size of existing muscle fibers or the addition of new muscle fibers. FO of the plantaris muscle, a calf muscle responsible for ankle extension, was performed in WT and MMP-9 knockout (MMP-9 KO) mice (~4 mos of age) by removing the soleus and gastrocnemius muscles and randomly placed into the following groups: 1) 2-day FO (n=5/group) and 14-day FO (n=5/group). A 0-day time point for each group was added as a baseline control (n=5/group). Fluorescence immunohistochemistry was performed using anti-Pax7 and anti-laminin antibodies to label satellite cells and the basal lamina, respectively. There was a general increase in satellite cells after 14-days FO compared to 0- and 2-days in both the WT and MMP-9 KO mice. There also was no observable trend or pattern in fiber count between time points for both WT and MMP-9 KO mice. However as the sample size is based on n=1 for each group at each time point no inference to statistical significance can be made. At this juncture, more samples are being analyzed to determine these relationships

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Calcineurin activates interleukin-6 transcription in mouse skeletal muscle in vivo and in C2C12 myotubes in vitro

Expression of the cytokine interleukin-6 (IL-6) by skeletal muscle is hugely increased in response to a single bout of endurance exercise, and this appears to be mediated by increases in intracellular calcium. We examined the effects of endurance exercise on IL-6 mRNA levels and promoter activity in skeletal muscle in vivo, and the role of the calcium-activated calcineurin signaling pathway on muscle IL-6 expression in vivo and in vitro. IL-6 mRNA levels in the mouse tibialis anterior (TA) were increased 2–10-fold by a single bout of treadmill exercise or by 3 days of voluntary wheel running. Moreover, an IL-6 promoter-driven luciferase transgene was activated in TA by both treadmill and wheel-running exercise and by injection with a calcineurin plasmid. Exercise also increased muscle mRNA expression of the calcineurin regulatory gene MCIP1, as did treatment of C2C12 myotubes with the calcium ionophore A23187. Cotransfection of C2C12 myotubes with a constitutively active calcineurin construct significantly increased while cotransfection with the calcineurin inhibitor CAIN inhibited activity of a mouse IL-6 promoter-reporter construct. Cotransfection with a myocyte enhancer-factor-2 (MEF-2) expression construct increased basal IL-6 promoter activity and augmented the effects of calcineurin cotransfection, while cotransfection with the MEF-2 antagonist MITR repressed calcineurin-activated IL-6 promoter activity in vitro. Surprisingly, cotransfection with a dominant-negative form of another calcineurin-activated transcription factor, nuclear factor activator of T cells (NFAT), greatly potentiated both basal and calcineurin-stimulated IL-6 promoter activity in C2C12 myotubes. Mutation of the MEF-2 DNA binding sites attenuated, while mutation of the NFAT DNA binding sites potentiated basal and calcineurin-activated IL-6 promoter activity. Finally, CREB and C/EBP were necessary for basal IL-6 promoter activity and sufficient to increase IL-6 promoter activity but had minimal roles in calcineurin-activated IL-6 promoter activity. Together, these results suggest that IL-6 transcription in skeletal muscle cells can be activated by a calcineurin-MEF-2 axis which is antagonized by NFAT

Voices of Adolescents on School Engagement

A limited number of empirical studies have been conducted to explore how students perceive school engagement and the factors influencing their engagement in school, particularly amongst Asian students. The purpose of this qualitative study was to understand school engagement from the perspectives of twenty-two secondary school students through two group interviews. Analysis was conducted using thematic analysis yielding themes based on deductive reasoning. Findings showed that the concept of school engagement was complex with relationships with peers and teachers emerging as the most dominant theme. The second most prominent theme was school participation and rules, followed by academic pursuits. The theme of school-contextual factors also emerged. Interestingly, a negative valence to school engagement was found. The findings of this study have the potential to inform researchers and practitioners in the on-going efforts to examine the concept of school engagement to further improve school system wide practices