Spatiotemporal distribution of PKCα, Cdc42, and Rac1 before directed cell migration.

Cdc42 is a key factor in directed cell migration and accumulates at the leading edge of migrating cells. However, what kind of proteins control Cdc42 and when is unclear. After mechanical wounding, protein kinase C α (PKCα), a conventional PKC isozyme, begins to accumulate at the edges of cells adjacent to the wounded cells (WCs). In this study, we hypothesized that PKCα may be implicated in directed cell migration at an early stage before Cdc42 controls the migration. We focused on the spatiotemporal distribution of PKCα, Cdc42, and Rac1 before cell migration. After wounding, at the edges of cells adjacent to the WCs, PKCα accumulation, Cdc42 accumulation, Rac1 accumulation, and filopodia formation occurred in that order. The PKCα inhibitor suppressed Cdc42 accumulation at the cell edges. These results suggest that inhibition of PKCα activity inhibits cell migration. In addition, it is not Cdc42 but PKCα that may decide the direction of cell migration.

Design of Low-Cost Modular Bio-Inspired Electric-Pneumatic Actuator (EPA)-Driven Legged Robots.

Exploring the fundamental mechanisms of locomotion extends beyond mere simulation and modeling. It necessitates the utilization of physical test benches to validate hypotheses regarding real-world applications of locomotion. This study introduces cost-effective modular robotic platforms designed specifically for investigating the intricacies of locomotion and control strategies. Expanding upon our prior research in electric-pneumatic actuation (EPA), we present the mechanical and electrical designs of the latest developments in the EPA robot series. These include EPA Jumper, a human-sized segmented monoped robot, and its extension EPA Walker, a human-sized bipedal robot. Both replicate the human weight and inertia distributions, featuring co-actuation through electrical motors and pneumatic artificial muscles. These low-cost modular platforms, with considerations for degrees of freedom and redundant actuation, (1) provide opportunities to study different locomotor subfunctions-stance, swing, and balance; (2) help investigate the role of actuation schemes in tasks such as hopping and walking; and (3) allow testing hypotheses regarding biological locomotors in real-world physical test benches.

Enhancing postural stability in a musculoskeletal hopping robot through stretch reflex application on biarticular thigh muscles.

Postural stabilization during rapid and powerful hopping actions represents a significant challenge for legged robotics. One strategy utilized by humans to negotiate this difficulty is the robust activation of biarticular thigh muscles. Guided by this physiological principle, this study aims to enhance the postural stability of a hopping robot through the emulation of this human mechanism. A legged robot powered by pneumatic artificial muscles (PAMs) was designed to mimic human anatomical structures. A critical aspect of this development was creating a tension-oriented stretch reflex system engineered to initiate muscle activation in response to perturbations. Our research encompassed three experiments: 1) assessing the trunk pitch angle with and without the integration of stretch reflexes, 2) evaluating the consistency of hops made with and without reflexes, and 3) understanding the correlation between the reflex strength equilibrium in the biarticular thigh muscles and trunk pitch angle. The results indicated that the integration of the stretch reflex minimized perturbations, thereby allowing the robot to perform double the continuous hops. As hypothesized, adjusting the reflex strength equilibrium caused a shift in the angle. This reflex mechanism offers potential application to PAM-driven robots and signifies a promising avenue for enhancing postural stability in diverse forms of locomotion, including walking and running.

Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT): a multicenter, randomized, open-label, parallel-group study.

INTRODUCTION: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). RESEARCH DESIGN AND METHODS: Changes in mean daily blood glucose level before and after 48-72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. RESULTS: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183-156 mg/dL, p=0.001), maximum glucose (300-253, p<0.01), and SD glucose (57-45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2'-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. CONCLUSIONS: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48-72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in 'time in ranges' and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies. TRIAL REGISTRATION NUMBER: UMIN000019457.