Biology subjects

Shiozawa, K.

Publications and source records attributed to Shiozawa, K..

4 recordsLinked to original sources

bioRxiv2025

Foot-Ground Force Quantifies Impaired Balance Control Mechanisms Post-Stroke

Approximately 50% of stroke survivors experience lasting balance impairments that persist and that are often managed through compensatory, but suboptimal, strategies. Identifying neuromechanical control changes after stroke could enable more targeted and effective rehabilitation strategies. Computational modeling has begun to uncover balance control strategies in unimpaired adults, but efforts have been limited post-stroke. Here we show one of the first instances of a model of quiet stance that reveals distinct control strategies in post-stroke individuals compared to similarly-aged unimpaired participants. Quiet standing was modeled using a double-inverted pendulum with full-state feedback control. The controller parameters were fit to foot-ground force data collected from 12 post-stroke and 22 similarly-aged unimpaired participants. The best-fit models revealed a joint-torque-coordination pattern in the paretic limb of post-stroke participants that differed substantially from that of the unimpaired participants. The post-stroke participants non-paretic limb also showed increased reliance on neural feedback, which may quantify compensatory effort for the altered coordination in the paretic limb. The results demonstrate that model-based analysis of foot-ground force behavior can reveal clinically meaningful insights that are not captured by traditional assessments.

physiology↗

bioRxiv2024

Human foot force reveals different balance control strategies between healthy younger and older adults

Aging can cause the decline of balance ability, which can lead to increased falls and decreased mobility. This work aimed to discern differences in balance control strategies between healthy older and younger adults. Foot force data of 38 older and 65 younger participants (older and younger than 60 years, respectively) were analyzed. To first determine whether the two groups exhibited any differences, this study incorporated the orientation of the foot-ground interaction force in addition to its point of application. Specifically, the frequency-dependence of the "intersection point" of the lines of actions of the foot-ground interaction force were evaluated. Results demonstrated that, like the mean center-of-pressure speed, a traditionally-employed measure, the intersection-point analysis could distinguish between the two participant groups. Then, to further explore age-specific control strategies, simulations of standing balance were conducted. An optimal controller stabilized a double-inverted-pendulum model with torque-actuated ankle and hip joints corrupted with white noise. The experimental data were compared to the simulation results to identify the controller parameters that best described the human data. Older participants showed significantly more use of the ankle than hip compared to younger participants. Best-fit controller gains suggested diminished intrinsic muscle stiffness in older adults, indicative of muscle strength loss, that was likely compensated by increased neural feedback. These results underscore the advantages of the intersection-point analysis to quantify shifts in interjoint control strategies with age, thus highlighting its potential to be used as a balance assessment tool in research and clinical settings. NEW & NOTEWORTHYAge groups were distinguished by analyzing foot-ground force data during quiet standing in older and younger adults to calculate the foot-force vector intersection point that emerges across frequency bands. Modeling balance and comparing the simulations outcomes with experimental results suggested that older adults increased reliance on neural feedback, possibly compensating for muscle strength deficiency. This novel analysis also quantified controllers for each participant, highlighting its potential to be implemented as a balance assessment tool.

physiology↗

bioRxiv2024

Human Foot Force Informs Balance Control Strategies when Standing on a Narrow Beam

Despite the abundance of studies on the control of standing balance, insights about the roles of biomechanics and neural control have been limited. Previous work introduced an analysis combining the direction and orientation of ground reaction forces. The "intersection point" of the lines of actions of these forces exhibited a consistent pattern across healthy, young subjects when computed for different frequency components of the center of pressure signal. To investigate the control strategy of quiet stance, we applied this intersection point analysis to experimental data of 15 healthy, young subjects balancing in tandem stance on a narrow beam and on the ground. Data from the sagittal and frontal planes were analyzed separately. The task was modeled as a double-inverted pendulum controlled by an optimal controller with torque-actuated ankle and hip joints and additive white noise. To test our prediction that the controller that minimized overall joint effort would yield the best fit across the tested conditions and planes of analyses, experimental results were compared to simulation outcomes. The controller that minimized overall effort produced the best fit in both balance conditions and planes of analyses. For some conditions, the relative penalty on the hip and ankle joints varied in a way relevant to the balance condition or to the plane of analysis. These results suggest that unimpaired quiet balance in a challenging environment can be best described by a controller that maintains minimal effort through the adjustment of relative ankle and hip joint torques. NEW & NOTEWORTHYThis study explored balance control in humans during a challenging task using the novel intersection point analysis, based on ground reaction force direction and point of application. Experimental data of subjects standing on a narrow beam in tandem stance were compared with modeling results of a double-inverted pendulum. The analysis showed that individuals minimized effort by adjusting ankle and hip torques, shedding light on the interplay of biomechanics and neural control in maintaining balance.

physiology↗

bioRxiv2019

CDK1 dependent phosphorylation of hTERT contributes to cancer progression

The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses revealed that phosphorylation of hTERT at threonine 249 occurs more frequently in advanced cancers. Using CRISPR/Cas9 genome editing, we introduced substitution mutations at threonine 249 in the endogenous hTERT locus and found that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase activity. Cap Analysis of Gene Expression (CAGE) demonstrated that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomerase independent manner.

cancer biology↗