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Tumer, N.

Publications and source records attributed to Tumer, N..

2 recordsLinked to original sources

Co-contraction index improves estimates of knee joint contact forces: A musculoskeletal modelling study

Healthy individuals are hypothesized to adopt muscle coordination strategies that minimize energy expenditure. However, under pathological conditions, these patterns often change, as patients adopt alternative strategies to enhance stability. In musculoskeletal modeling, such changes in muscle coordination are often not accounted for when estimating internal quantities such as knee joint contact forces. To address this, we adapted the objective function of a muscle redundancy solver to inform muscle activations from electromyography measurements, minimizing errors in both muscle activations and co-contraction levels. The resulting estimates of knee joint contact force were compared with in vivo measurements across three activities. The co-contraction index-informed approach achieved the lowest root-mean-square-error of 0.31 body weight, averaged across all subjects and activities, improving the results of the minimum activation solver by 7% body weight. Notably, root-mean-squared-error increased with the level of co-contraction with the minimum activation approach ({beta} = 1.55, 95% confidence interval [0.79, 2.30]), whereas the co-contraction index-informed approach remained less sensitive ({beta} = 0.78, 95% confidence interval [0.14, 1.43]). These findings suggest that objective functions based on minimum muscle activation may be insufficient to accurately estimate knee joint forces in individuals with altered muscle coordination. Incorporating co-contraction information is therefore essential to capture subject-specific adaptations.

bioengineering↗

Intracellular Neutralization of Ricin Toxin by Single Domain Antibodies Targeting the Active Site Pocket

The extreme potency of the plant toxin, ricin, is due to its enzymatic subunit, RTA, which inactivates mammalian ribosomes with near perfect efficiency. Here we characterized, at the functional and structural levels, seven alpaca single-domain antibodies (VHHs) previously reported to recognize epitopes in proximity to RTAs active site. Three of the VHHs, V2A11, V8E6 and V2G10, were potent inhibitors of RTA in vitro and protected Vero cells from ricin when expressed as intracellular antibodies (\"intrabodies\"). Crystal structure analysis revealed that the complementarity-determining region 3 (CDR3) elements of V2A11 and V8E6 penetrate RTAs active site and interact with key catalytic residues. V2G10, in contrast, sits atop the enzymatic pocket and occludes substrate accessibility. The other four VHHs also penetrated/occluded RTAs active site, but lacked sufficient binding affinities to outcompete RTA-ribosome interactions. Intracellular delivery of high-affinity, single-domain antibodies may offer a new avenue in the development of countermeasures against ricin toxin.

immunology↗