Crosby, K. | bioRxiv Science

bioRxiv2025

Value-Added: Importance of Incorporating Menstrual Cycle Phases to Clarify Sex-Related Differences in Force Steadiness

AimThis study aimed to determine whether female elbow flexion force steadiness varies across the menses, follicular and luteal phases of the menstrual cycle. MethodsTo control for repeated testing effects unrelated to hormonal fluctuations across the menstrual cycle, a comparison group of males completed the same protocol over three equally spaced testing sessions to the females. Maximal voluntary contractions and force steadiness were assessed in the neutral and pronated forearm positions. Elbow flexion force tracking tasks were performed at 2.5, 5, 10, 25, 50 and 75% maximal voluntary contraction in both forearm positions, and force steadiness was quantified as the coefficient of variation of force. ResultsMales were stronger than females (p<0.001), and maximal voluntary contractions did not differ between menstrual phases (p>0.14) or between days in males (p>0.56) in both forearm positions. There was no difference in coefficient of variation of force across sessions for the males (p<0.36). The coefficient of variation of force for all submaximal forces was significantly greater during the luteal phase compared to menses (Neutral p=0.02; Pronated p<0.05) but not the follicular phase (Neutral p=0.71; Pronated p=0.10). The coefficient of variation of force during the luteal phase in females was higher than males in both positions (p<0.02). ConclusionThese findings support previous observations that females are less steady than males for isometric steady contractions; however, this study identifies luteal specific phase effects. This underscores the importance of accounting for menstrual cycle phase when conducting sex-related comparisons.

physiology↗

bioRxiv2018

Loss of charge at solvent exposed Lys residues does not induce the aggregation of superoxide dismutase 1

Mutations in superoxide dismutase 1 (SOD1) associated with familial amyotrophic lateral sclerosis (fALS) induce the protein to misfold and aggregate. To date, missense mutations at more than 80 different amino acid positions have been associated with disease. How these mutations perturb native structure to heighten the propensity to misfold and aggregate is unclear. One potential mechanism that has been suggested is that when mutations occur at positions occupied by charged amino acids, then repulsive forces that would inhibit aberrant protein:protein interactions would be reduced. Mutations at twenty-one charged residues in SOD1 have been associated with fALS. Here, we examined whether loss of positively charged surface Lys residues would induce the misfolding and aggregation of SOD1. We randomly mutated four different Lys residues (K30, K36, K75, K91) in SOD1 and expressed these variants as fusion proteins with yellow fluorescent protein (YFP). We also assessed whether these mutations induced binding to a conformation-restricted SOD1 antibody, designated C4F6, which recognizes non-natively folded protein. Our findings indicate that SOD1 generally tolerates mutations at surface exposed lysine residues, and that loss of positive charge is insufficient to induce aggregation. Our findings may explain why mutations at these Lys residues have not been identified in ALS patients.

biochemistry↗