Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.     

On-off switching properties of one-dimensional photonic crystals consisting of azo-functionalized polymer liquid crystals having different methylene spacers and polyvinyl alcohol

In this paper, photoresponsive behavior of multi-bilayered films having precisely controlled layer thickness prepared by stacking an azo-functionalized polymer liquid crystal, PMAzXAc, and polyvinyl alcohol alternatively, PVA, is described. The multi-bilayered films were found to reflect a light of specific wavelength depending on the layer thickness and refractive index, and showed the reversible change in the reflection intensity by irradiation with visible and UV lights. The change in the reflection intensity was brought about by change in the molecular orientation of PMAzXAc between an out-of-plane orientation and a photo-induced isotropic state, and was strongly dependent on the number of methylene spacer of PMAzXAc linking the azobenzene side group with the acrylate polymer main chain. PMAz6Ac with hexa-methylene spacer showed the largest change in the reflection intensity, while smaller change in the reflection intensity was observed for PMAzXAc having shorter or longer methylene spacer than 6. The effect of the methylene spacers on the photochemical change in the molecular orientation of azobenzene chromophores in the multi-bilayered films will be discussed.     

Synthesis and optical properties of azobenzene side chain polymers derived from the bifunctional fumaric acid and itaconic acid

Three type polymers containing the same azobenzene side chain group with different backbone structures, poly(DMAz6Fm), poly(DMAz6It) and poly(MAz6Ac) derived respectively from fumaric acid, itaconic acid and acrylic acid, were synthesized. The dependence of photo-response properties on the polymeric architecture was investigated for the solutions and films. By irradiation of the linearly polarized light (436 nm), uniaxial orientations of the thin films were induced and anisotropic properties were investigated by measurements of the order parameters and birefringence values.     

Dummy humanoid robot simulating several trunk postures and abdominal shapes – Report of element technologies

Development of clothing in consideration of the shape and body function of a person with spinal cord injury is an important task. Then, a dummy robot with a deformation mechanism was developed in this study for evaluating the comfortable level of clothings. Specifically, a trunk joint mechanism and an abdominal mechanism that can realize various deformations of the abdominal area and various trunk poses were developed. The trunk joint mechanism was implemented in order to simulate the seated posture of persons with spinal cord injury. The abdominal deformation mechanism was implemented using linear actuators and rotating servomotors in order to simulate abdominal obesity of persons with spinal cord injury. Further, a tactile sensor system was developed for measuring the clothing pressure on the abdominal area and evaluating the comfort or discomfort of clothing.     

Effect of α-substituents on molecular motion and wetting behaviors of poly(fluoroalkyl acrylate) thin films with short fluoroalkyl side chains

The effect of α-substituent on the molecular motion and wetting behavior of poly{2-(perfluorobutyl)ethyl acrylate} [PFA-C₄], poly{2-(perfluorobutyl)ethyl methacrylate} [PFMA-C₄], poly{2-(perfluorobutyl)ethyl α-fluoroacrylate} [PFFA-C₄], and poly{2-(perfluorobutyl)ethyl α-chloroacrylate} [PFClA-C₄] films were characterized by dynamic contact angle measurement, lateral force microscopy (LFM), wide angle X-ray diffraction (WAXD), and X-ray photoelectron spectroscopy (XPS). WAXD of oriented PFClA-C₄ fiber suggested the presence of rod-like chain due to the presence of bulky α-substituent. The glass transition temperature (T_g) of PFFA-C₄ and PFClA-C₄ were well above the room temperature. The water repellencies of PFFA-C₄ and PFClA-C₄ were as high as that of PFMA-C₄ and their oil repellency of PFFA-C₄ and PFClA-C₄ was higher than the PFMA-C_4. This result was originated from the low main chain mobility of PFFA-C₄ and PFClA-C₄ due to the presence of bulky α-substituents. The effect of molecular motion on water repellency was clarified by the results of temperature dependence studies of dynamic contact angle, LFM, and surface chemical composition measured by XPS.     

A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.     

Evaluation of standing‐sitting support system with passive rotational seat mechanism in standing motion

Since a decrease in muscle mass of elderly people, the physical burden of them in standing‐sitting motion of a seat are increasing than young people. For this problem, several standing‐sitting support systems have been developed, and evaluations of these systems focusing on a reduction of physical load have been discussed. However, these evaluations are of support systems with an active actuators or of support systems when they use a handrail and a standing aid. Thus, an evaluation of a support system with only passive actuators has not been reported. In this paper, in standing motion with using a standing‐sitting support system with passive rotational seat mechanism which our group proposes, we objectively evaluate an effectiveness of the passive rotational seat mechanism by statistical analysis.