Eaton, A. J. | bioRxiv Science

bioRxiv2024

Simulations reveal how touchdown kinematic variables affect top sprinting speed: implications for coaching

Sprint performance is a priority for coaches and athletes. Several kinematic variables, including horizontal touchdown distance (HTD) and inter-knee touchdown distance (IKTD), are targeted by coaches to increase top sprinting speed. However, the results of past research are conflicting, potentially due to the use of experimental inter-athlete study designs where it is not possible to establish cause-effect relationships. In this study, we used a predictive simulation approach to assess cause-effect relationships between HTD and IKTD and sprinting speed. We scaled a three-dimensional musculoskeletal model to match the anthropometry of an international caliber male sprinter, and generated predictive simulations of a single symmetric step of top-speed sprinting using a direct collocation optimal control framework. We first used our simulation framework to establish the models top speed with minimal constraints on touchdown kinematics (the optimal simulation). Then, in additional simulations we enforced specific HTD or IKTD values ({+/-} 2, 4 and 6 cm compared to optimal). The model achieved a top speed of 11.85 m/s in the optimal simulation. Shortening HTD by 6 cm reduced speed by 7.3%, while lengthening HTD by 6 cm had a smaller impact on speed, with a 1.6% reduction. Speed in the simulation was insensitive to the IKTD changes we tested. The results of our simulations indicate there is an optimal HTD to maximize sprinting speed, providing support for coaches and athletes to adjust this technique variable. Conversely, our results do not provide evidence to support utilizing IKTD as a key technique variable for speed enhancement. We share the simulation framework so researchers can explore the effects of additional modifications on sprinting performance (https://github.com/nicos1993/Pred_Sim_Sprinting).

bioengineering↗

bioRxiv2020

A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne-Kalscheuer syndrome

Tonne-Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability syndrome associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS is caused exclusively by variants in the gene encoding the E3 ubiquitin ligase gene RLIM, also known as. Here we report identification of a novel RLIM missense variant, c.1262A>G p.(Tyr421Cys) adjacent to the regulatory basic region, which causes a severe form of TOKAS resulting in perinatal lethality by diaphragmatic hernia. Inheritance and X-chromosome inactivation patterns implicate RLIM p.(Tyr421Cys) as the likely pathogenic variant in the affected individual and within the kindred. We show that the RLIM p.(Tyr421Cys) variant disrupts both expression and function of the protein in an embryonic stem cell model. RLIM p.(Tyr421Cys) is correctly localised to the nucleus, but is readily degraded by the proteasome. The RLIM p.(Tyr421Cys) variant also displays significantly impaired E3 ubiquitin ligase activity, which interferes with RLIM function in Xist long-non-coding RNA induction that initiates imprinted X-chromosome inactivation. Our data uncover a highly disruptive missense variant in RLIM that causes a severe form of TOKAS, thereby expanding our understanding of the molecular and phenotypic spectrum of disease severity.

developmental biology↗