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Yoshioka, S.

Publications and source records attributed to Yoshioka, S..

4 recordsLinked to original sources

Novel humanized anti-Nav1.7 antibodies with long-lasting, side-effect-free analgesic effects

Neuropathic pain remains difficult to treat effectively because of the limitations of current pain medications. The Nav1.7 sodium channel plays a crucial role in pain sensation. The development of selective inhibitors has been challenging because of the high similarity among Nav channel subtypes. To address this issue, we developed monoclonal antibodies that selectively target Nav1.7 and humanized them for clinical use for the first time. When administered systemically to neuropathic pain model rats, a potent analgesic effect was observed that lasted for at least 96 hours. Electrophysiological studies revealed that the antibody reduced mechanically-evoked and spontaneous neuronal activity in the model. Importantly, the antibodies did not impact physiological pain or motor function. Collectively, our findings suggest that these novel Nav1.7-targeting antibodies are potentially effective analgesic drugs for chronic pain, including neuropathic pain. Our novel humanized anti-Nav1.7 antibodies have the potential to be used for the development of new analgesic, and one such antibody, S-151128 is currently in clinical trial.

pharmacology and toxicology↗

Hepatocytes with a phenotype of substantial CYP3A4 induction generated from drug-associated fulminant hepatitis-derived induced pluripotent stem cells

Hepatocyte-like cells (HLCs) generated from human pluripotent stem cells (PSCs) exhibit hepatocytic properties in vitro; however, their engraftment and functionality in vivo remain unsatisfactory. Despite optimization of differentiation protocols, HLCs did not engraft in a mouse model of liver injury. In contrast, organ-derived hepatocytes reproducibly formed colonies in the liver injury mouse model. As an extension of the phenomenon observed in hematopoietic stem cells giving rise to colonies within the spleen, commonly referred to as "colony-forming units in spleen (CFU-s", we hypothesize that "colony-forming units in liver (CFU-L)" serves as a reliable indicator of stemness, engraftment, and functionality of hepatocytes. The uniform expression of the randomly inactivated gene in a single colony, as reported by Sugahara et al. 2022, suggests that the colonies generated by isolated hepatocytes likely originate from a single cell. We, therefore, propose that CFU-L can be used to quantify the number of "hepatocytes that engraft and proliferate in vivo" as a quantitative assay for stem cells that utilize colony-forming ability, similar to that observed in hematopoietic stem cells.

cell biology↗

Evaluation of 3D markerless motion capture accuracy using OpenPose with multiple video cameras

There is a need within human movement sciences for a markerless motion capture system, which is easy to use and suffciently accurate to evaluate motor performance. This study aims to develop a 3D markerless motion capture technique, using OpenPose with multiple synchronized video cameras, and examine its accuracy in comparison with optical marker-based motion capture. Participants performed three motor tasks (walking, countermovement jumping, and ball throwing), with these movements measured using both marker-based optical motion capture and OpenPose-based markerless motion capture. The differences in corresponding joint positions, estimated from the two different methods throughout the analysis, were presented as a mean absolute error (MAE). The results demonstrated that, qualitatively, 3D pose estimation using markerless motion capture could correctly reproduce the movements of participants. Quantitatively, of all the mean absolute errors calculated, approximately 47% were less than 20 mm and 80% were less than 30 mm. However, 10% were greater than 40 mm. The primary reason for mean absolute errors exceeding 40mm was that OpenPose failed to track the participants pose in 2D images owing to failures, such as recognition of an object as a human body segment, or replacing one segment with another depending on the image of each frame. In conclusion, this study demonstrates that, if an algorithm that corrects all apparently wrong tracking can be incorporated into the system, OpenPose-based markerless motion capture can be used for human movement science with an accuracy of 30mm or less.

neuroscience↗

Skilled strategies of release parameters for accurate free-throw shooting in the presence of motor noise

How humans execute accurate movement in the presence of motor noise is a key problem in the field of biomechanics and motor control that limits the performance improvement in daily or sporting activities. The aim of this study was to clarify the strategy of basketball players during free-throw shooting. Two possible hypotheses were examined: the players minimize the release speed to decrease signal-dependent noise or the players maximize the shot success probability by accounting for their variability. Eight collegiate players and one professional player participated in this study by attempting shots from the free-throw line using a motion capture system. The solution manifold consisting of ball parameters at release was calculated and the optimal strategy was simulated by considering ball parameter variability; this result was compared with the actual data. Our results showed that participants selected the solution of near-minimum release speed. The deviation of the measured release angle from the minimum-speed angle was close to zero (2.8 {+/-} 3.1{degrees}). However, an increase in speed-dependent noise did not have a significant influence on the ball landing position through simulation. Additionally, the effect of release angle error on the ball landing position was minimum when using the minimum speed strategy. Therefore, the players minimize the release speed to minimize the effect of the release error on performance, instead of minimizing the speed-dependent noise itself. In other words, the strategy is \"near-minimum-speed strategy\" as well as \"minimum-error-propagation strategy\". These findings will be important for understanding how sports experts deal with intrinsic noise to improve performance.

neuroscience↗