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Data and data collection tool from Kirk et al. 2021 MMA training load study published in PLoS One

Glucocorticoid (GC) resistance is a poor prognostic factor in T-cell acute lymphoblastic leukaemia (T-ALL). Interleukin-7 (IL-7) mediates GC resistance via GC-induced upregulation of IL-7 receptor (IL-7R) expression, leading to increased pro-survival signalling. IL-7R reaches the cell surface via the secretory pathway, so we hypothesized that inhibiting the translocation of IL-7R into the secretory pathway would overcome GC resistance. Sec61 is an endoplasmic reticulum (ER) channel that is required for insertion of polypeptides into the ER. Here, we demonstrate that KZR-445, a novel inhibitor of Sec61, potently attenuates the dexamethasone (DEX)-induced increase in cell surface IL-7R and overcomes IL-7-induced DEX resistance.

Physiological changes brought about by a person’s aging process are known to negatively affect elite sports performance, but this may be delayed by skill mastery brought about by continued training. The intersection of these two separate processes causes a potential ‘peak performance window’ in many sports. Within MMA it has been shown that older competitors are more likely to lose individual bouts, especially due to strikes, and when they win it is most likely to be due to a decision. It has not been determined whether age has a long-term effect on success in MMA. This study divided the top 100 competitors in each MMA weight division into 5 ranking groups (RG) and used Bayesian ANOVA (BF10), 95% credible interval plots and Bayesian Kendall’s Tau (BF10) to determine if competitor rankings are affected by their age, and if each division displays a different age profile. The results found that whilst there is a general pattern of older participants being ranked higher, middleweight was the only division where this was statistically relevant. It was found, however, that the heavier the mass limit of the division, the older the participants are across each RG. These results suggest that skill mastery may be of more short-term importance to successful performance in MMA than physiological ability, particularly in the heavier divisions, but physiological decrements effect lighter competitors earlier in their chronological age. This is potentially due to differing performance requirements between the different divisions.

In addition to antigen processing, immunoproteasomes were recently shown to exert functions influencing cytokine production by monocytes and T cells, T-helper cell differentiation, and T-cell survival. Moreover, selective inhibition of the immunoproteasome subunit LMP7 ameliorated symptoms of autoimmune diseases including CD4(+) T-cell mediated EAE. In this study, we show that LMP7 also plays a crucial role in the pathogenesis of lymphocytic choriomeningitis virus (LCMV)-induced meningitis mediated by CTLs. Mice lacking functional LMP7 display delayed and reduced clinical signs of disease accompanied by a strongly decreased inflammatory infiltration into the brain. Interestingly, we found that selective inhibition and genetic deficiency of LMP7 affect the pathogenesis of LCMV-induced meningitis in a distinct manner. Our findings support the important role of LMP7 in inflammatory disorders and suggest immunoproteasome inhibition as a novel strategy against inflammation-induced neuropathology in the CNS.