Posture Operating Method by Foot Posture Change and Characteristics of Foot Motion

The lower limbs of the human body actually can perform the multiple-degree-of-freedom motion, just like the upper limbs. This suggests the possibility for the lower limbs to be used in the operation of multiple-degree-of-freedom devices, such as a robot arm. With that point in mind, the present paper focuses on the foot motion and examines its characteristics under the situation in which the posture of the object is manipulated by the posture change of the foot. First, we investigated how well the foot of the operator moved in accordance with the intention of the operator in order to clarify the motion characteristics of the foot experimentally by measuring the foot motion with a motion capture system under the assumption that the operator manipulates an object in virtual space. The results showed that there are differences between the intended and actual foot motions, especially when the tilt angle change was accompanied by a rotation angle change, which might be because of the joints whose axes of motion are nonparallel to the foot coordinate system, such as the talocalcaneal joint or Chopart joint. Next, an operating system considering the motion characteristics of the foot was proposed, and an experiment to verify its effectiveness was conducted. When the proposed conversion formula was used to calculate the intended foot motion based on the actual foot motion, the operability improved with respect to the required time and path-following accuracy while manipulating an object to the target posture and with respect to subjective operability

Analysis of Effect of Motion Path on Leg Muscle Load and Evaluation of Device to Support Leg Motion During Robot Operation by Reducing Muscle Load

Because the human arm and leg have a similar skeletal structure, it may be possible to use the leg to operate a robot by the master-slave method. However, operation by the leg with six degrees of freedom has two problems. First, people move their ankle with a curved motion despite intending to move it linearly. Second, it is a burden for the operator to suspend their legs in the air during operation. This study dealt with these problems. For the first problem, we hypothesized that one of the reasons was that the muscle load of a curved motion was smaller than that of a linear motion, and we quantitatively compared them by musculoskeletal analysis. The muscle loads of curved motions were 20% smaller in the anteroposterior direction, 3.1% to 23.8% smaller in the lateral direction, and 10% smaller in the vertical direction than linear motions, which showed that the hypothesis was consistent. Further, comparison of the analysis results with the results of a previous study suggested that subjects unconsciously tried to reduce the muscle load and to move closer to a linear line when they moved their ankle while consciously intending to make a linear motion. For the second problem, we developed two different prototypes of a leg support device. An experiment to evaluate the effectiveness of these devices showed that subjective exercise intensity of the tasks in the experiment using the devices was 40% or more less than that without the device, which proved the effectiveness of the devices

Pseudosarcomatous Proliferation of Cx43- and Kit-Expressing Interstitial Cell in the Urinary Bladder

The authors report a case showing proliferation of KIT- and connexin 43-expressing mesenchymal cells of the urinary bladder. A 75-year-old woman had an ulcerated endophytic mass (size, approximately 2 × 2 cm) in the left posterolateral wall. She underwent transurethral resection and subsequent partial cystectomy. The suburothelial mass extended to the muscularis propria. The histopathological analysis revealed spindle-shaped mesenchymal cells that were loosely arranged with myxoid stroma and showed a focal compact fascicular arrangement. In the immunohistochemical analysis, these spindle cells were stained with specific antibodies to KIT and connexin 43. The patient is currently free of disease at 5 years after operation. The proliferating spindle cells in the present case might represent a phenotype of interstitial cells of the lamina propria

Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites

The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism

Transcriptional regulation of chondrogenesis by coactivator Tip60 via chromatin association with Sox9 and Sox5

Sox9 is a transcription factor of the SRY family required for several steps of chondrogenesis. It activates the expression of various chondrocyte-specific genes, but the mechanisms and role of cofactors involved in Sox9-regulated gene transcription are not fully understood. Here, we report on the characterization of a Tat interactive protein-60 (Tip60) as Sox9-associated protein identified in a yeast two-hybrid screen. Both in vitro and in vivo assays confirmed the specificity of interactions between Sox9 and Tip60 including the existence of an endogenous complex containing both polypeptides in chondrocytes. Gel shift assays showed the presence of a complex containing Sox9, Tip60 and the DNA of an enhancer region of the Col2a1 promoter. Reporter assays using a Col2a1 promoter with multimerized Col2a1 Sox9-binding sites indicated that Tip60 enhanced the transcriptional activity of Sox9. A larger Col2a1 promoter showed that Tip60 increased the activity of this promoter in the presence of both Sox9 and Sox5. Ectopic expression of Sox9 and transient-cotransfection with Tip60 in COS7 cells showed a more diffuse subnuclear colocalization, suggesting changes in the chromatin structure. Chromatin immunoprecipitation assays showed that Tip60, Sox9 and Sox5 associated with the same Col2a1 enhancer region. Consistent with a role of Tip60 in chondrogenesis, addition of Tip60 siRNA to limb-bud micromass cultures delayed chondrocyte differention. Tip60 enhances acetylation of Sox9 mainly through K61, 253, 398 residues; however, the K61/253/398A mutant of Sox9 still exhibited enhanced transcriptional activity by Tip60. Our results support the hypothesis that Tip60 is a coactivator of Sox9 in chondrocytes

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated