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Age trends in record running performances, over distances from 100 yards to the marathon, were analyzed for males between 40–74 years. Within event distances, an exponential model most accurately related performance time to age. In terms of this model, rate of age decline in running performance was greater for middle and longer distance events than for sprints. Within age-levels, linear and power models were highly accurate in relating performance time to event distance. A general model, that proved highly accurate in accounting for variance in performance times over the full age and distance ranges, expressed performance as the product of a power function of distance and an exponential function of age. Findings are discussed in terms of anaerobic and aerobic processes that underlie running performance at different event distances. [ABSTRACT FROM PUBLISHER]

N6 adenosine and C5 cytosine modification of mRNAs, tRNAs and rRNAs are regulated by the behaviour of distinct sets of writer, reader and eraser effector proteins which are conventionally considered to function independently. Here, we provide evidence of global cross-regulatory and functional interaction between the m 6 A and m 5 C RNA methylation systems. We first show that m 6 A and m 5 C effector protein transcripts are subject to reciprocal base modification supporting the existence of co-regulatory post-transcriptional feedback loops. Using global mass spectrometry proteomic data generated after biological perturbation to identify proteins which change in abundance with effector proteins, we found novel co-regulatory cellular response relationships between m 6 A and m 5 C proteins such as between the m 6 A eraser, ALKBH5, and the m 5 C writer, NSUN4. Gene ontology analysis of co-regulated proteins indicated that m 6 A and m 5 C RNA cross-system control varies across cellular processes, e.g. proteasome and mitochondrial mechanisms, and post-translational modification processes such as SUMOylation and phosphorylation. We also uncovered novel relationships between effector protein networks including contributing to intellectual disability pathways. Finally, we provided in vitro confirmation of colocalisation between m 6 A-RNAs and the m 5 C reader protein, ALYREF, after synaptic NMDA activation. These findings have important implications for understanding control of RNA metabolism, cellular proteomic responses, and brain disease mechanisms., (© 2024. The Author(s).)

B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Immunology.)

We have previously demonstrated that vascular sodium pump activity is stimulated in several rat models of hypertension. In addition, others have reported an upregulation of mRNA for the Na+,K+-ATPase alpha1-subunit in hypertension. To test the effect of sustained, cyclic, stretch-relaxation stimuli on the expression of alpha1- and alpha2-subunits of Na+,K+-ATPase in vascular smooth muscle cells, we used the Flexercell strain unit to stretch rat aortic smooth muscle cells for several days on a collagen-coated silicone elastomer substratum. Six-second cycles of stretch-relaxation were applied to obtain 10% average surface elongation (22% maximum) for 4 days. Control cells were not stretched but were grown on a similar surface. The effect of Gd3+, a blocker of stretch-activated channels, was also investigated. At the end of 4 days, protein expression of alpha1- and alpha2-subunits was determined by Western blot analysis. Intensity of the bands for alpha1- and alpha2-subunits was quantified with the use of a computerized image analyzer. In the stretched cells, both the alpha1- and the alpha2-subunit protein-band intensities were significantly increased compared with those of the non-stretched cells. Treatment with 50 micromol/L Gd3+ during the application of stretch prevented the upregulation of alpha2-expression but not that of alpha1-expression. Sodium pump activity, the functional counterpart of Na+,K+-ATPase, was inhibited as a result of stretch; Gd3+ had no effect on this variable. Our results suggest that in vascular smooth muscle, stretch may be a signal for the upregulation of both the alpha1- and alpha2-isoforms. However, a differential response of the two isoforms to the blocker of stretch-activated channels implies involvement of different mechanisms. This alteration in protein expression is not reflected in the function of the enzyme.