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Aim: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals. Method: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19–38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20–40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t‐tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups. Results: Baseline levels of gamma delta (TCRγδ+) T‐cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T‐cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (−11.1%, p < 0.01), despite similar ratings of perceived exertion. Interpretation: Elevated baseline TCRγδ+ T‐cells may indicate low‐grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T‐cells in individuals with CP may indicate the need for higher intensity during exercise. What this paper adds: TCRγδ+ T‐cell baseline levels are elevated in adults with cerebral palsy (CP).The CD8+ T‐cell response to exercise was blunted in adults with CP.Exercise intensity is decisive for CD8+ T‐cell responses in individuals with CP. [ABSTRACT FROM AUTHOR]

Pulsatile Myc induction, through epigenetic alterations, mediates several aspects of the exercise response and may restore muscle plasticity with age. Of the "Yamanaka factors" Oct3/4 , Sox2 , Klf4 , and c-Myc (OSKM), the transcription factor c-Myc (Myc) is the most responsive to exercise in skeletal muscle and is enriched within the muscle fiber. We hypothesize that the pulsatile induction of MYC protein after bouts of exercise can serve to epigenetically reprogram skeletal muscle toward a more resilient and functional state. [ABSTRACT FROM AUTHOR]

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth. Graphical Abstract [ABSTRACT FROM AUTHOR]

Roberts et al. have provided an insightful counterpoint to our review article on the utility of the synergist ablation model. The purpose of this review is to provide some further dialogue regarding the strengths and weaknesses of the synergist ablation model. Specifically, we highlight that the robustness of the model overshadows surgical limitations. We also compare the transcriptomic responses to synergist ablation in mice and resistance exercise in humans to identify common pathways. We conclude that "cell growth is cell growth" and that the mechanisms available to cells to accumulate biomass and increase in size are similar across cell types and independent of the rate of growth.

In cell biology, ribosomal RNA (rRNA) 2' O -methyl (2'- O -Me) is the most prevalent posttranscriptional chemical modification contributing to ribosome heterogeneity. The modification involves a family of small nucleolar RNAs (snoRNAs) and is specified by box C/D snoRNAs (SNORDs). Given the importance of ribosome biogenesis for skeletal muscle growth, we asked if rRNA 2'- O -Me in nascent ribosomes synthesized in response to a growth stimulus is an unrecognized mode of ribosome heterogeneity in muscle. To determine the pattern and dynamics of 2'- O -Me rRNA, we used a sequencing-based profiling method called RiboMeth-seq (RMS). We applied this method to tissue-derived rRNA of skeletal muscle and rRNA specifically from the muscle fiber using an inducible myofiber-specific RiboTag mouse in sedentary and mechanically overloaded conditions. These analyses were complemented by myonuclear-specific small RNA sequencing to profile SNORDs and link the rRNA epitranscriptome to known regulatory elements generated within the muscle fiber. We demonstrate for the first time that mechanical overload of skeletal muscle 1 ) induces decreased 2'- O -Me at a subset of skeletal muscle rRNA and 2 ) alters the SNORD profile in isolated myonuclei. These findings point to a transient diversification of the ribosome pool via 2'- O -Me during growth and adaptation in skeletal muscle. These findings suggest changes in ribosome heterogeneity at the 2'- O -Me level during muscle hypertrophy and lay the foundation for studies investigating the functional implications of these newly identified "growth-induced" ribosomes. NEW & NOTEWORTHY Ribosomal RNAs (rRNAs) are posttranscriptionally modified by 2' O -methyl (2'- O -Me). This study applied RiboMeth-seq (RMS) to detect changes in 2'- O -Me levels during skeletal muscle hypertrophy, uncovering transient diversification of the ribosome pool in skeletal muscle fibers. This work implies a role for ribosome heterogeneity in skeletal muscle growth and adaptation.