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Miyamoto Y.,National Health Research Institute | Torii T.,National Health Research Institute | Yamamori N.,National Health Research Institute | Yamamori N.,Tokyo Institute of Technology | And 4 more authors.
Science Signaling

During neuronal development, axons navigate long distances, eventually forming precise connections with such targets as peripheral tissues. Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton. We found that phosphorylation of Ser1194 in Dock6 inhibited its GEF activity and suppressed axonal growth of embryonic sensory neurons and axon regeneration of postnatal sensory neurons in vitro and in vivo. At early developmental stages, when axons are growing, the protein phosphatase PP2A interacted with and dephosphorylated Dock6, thereby increasing the activity of Dock6. At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser 1194. In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching. Thus, the phosphorylation status of Dock6 at Ser1194 determines whether it promotes axon extension or branching in sensory neurons, revealing interplay between kinase and phosphatase action on a Rho-GEF during axon growth. Source

Yoshimura N.,Tokyo Medical University | Muraki S.,Tokyo Medical University | Oka H.,Tokyo Medical University | Tanaka S.,University of Tokyo | And 3 more authors.
Osteoarthritis and Cartilage

Objective: To clarify the association between the occurrence and progression of knee osteoarthritis (KOA) with components of metabolic syndrome (MS), including overweight (OW), hypertension (HT), dyslipidaemia (DL), and impaired glucose tolerance (IGT), in a general population. Design: From the large-scale population-based cohort study entitled Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) initiated in 2005, 1,690 participants (596 men, 1,094 women) residing in mountainous and coastal areas were enrolled. Of these, 1,384 individuals (81.9%; 466 men, 918 women) completed the second survey, including knee radiography, 3 years later. KOA was defined as Kellgren-Lawrence (KL) grade ≥ 2 using paired X-ray films. Based on changes in KL grades between the baseline and second surveys, cumulative incidence and progression of KOA were determined. OW, HT, DL, and IGT at baseline were assessed using standard criteria. Results: The cumulative incidence of KOA among 1,384 completers over 3 years was 3.3%/year, and progression in KL grades for either knee, 8.0%/year. Logistic regression analyses after adjusting for potential risk factors revealed that the odds ratio (OR) for the occurrence of KOA significantly increased according to the number of MS components present (OR vs no component: one component, 2.33; two components, 2.82; ≥three components, 9.83). Similarly, progression of KOA significantly increased according to the number of MS components present (OR vs no component: one component, 1.38; two components, 2.29; ≥three components: 2.80). Conclusion: Accumulation of MS components is significantly related to both occurrence and progression of KOA. MS prevention may be useful in reducing future KOA risk. © 2012 Osteoarthritis Research Society International. Source

Seki Y.,Japan National Institute of Advanced Industrial Science and Technology | Sato T.,National Rehabilitation Center for Persons with Disabilities
IEEE Transactions on Neural Systems and Rehabilitation Engineering

A new auditory orientation training system was developed for blind people using acoustic virtual reality (VR) based on a head-related transfer function (HRTF) simulation. The present training system can reproduce a virtual training environment for orientation and mobility (O&M) instruction, and the trainee can walk through the virtual training environment safely by listening to sounds such as vehicles, stores, ambient noise, etc., three-dimensionally through headphones. The system can reproduce not only sound sources but also sound reflection and insulation, so that the trainee can learn both sound location and obstacle perception skills. The virtual training environment is described in extensible markup language (XML), and the O&M instructor can edit it easily according to the training curriculum. Evaluation experiments were conducted to test the efficiency of some features of the system. Thirty subjects who had not acquired O&M skills attended the experiments. The subjects were separated into three groups: a no-training group, a virtual-training group using the present system, and a real-training group in real environments. The results suggested that virtual-training can reduce veering more than real-training and also can reduce stress as much as real training. The subjective technical and anxiety scores also improved. © 2010 IEEE. Source

Akune T.,University of Tokyo | Muraki S.,University of Tokyo | Oka H.,University of Tokyo | Tanaka S.,University of Tokyo | And 3 more authors.
Osteoporosis International

The present cross-sectional study investigated the prevalence of sarcopenia and clarified its associated factors in 1,000 elderly participants of Japanese population-based cohorts. Exercise habit in middle age was associated with low prevalence of sarcopenia in older age, suggesting that it is a protective factor against sarcopenia in older age. Introduction: The present study investigated the prevalence of sarcopenia using the European Working Group on Sarcopenia in Older People (EWGSOP) definition, and clarified the association of sarcopenia with physical performance in the elderly participants of Japanese population-based cohorts of the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study. Methods: We enrolled 1,000 participants (aged ≥65 years) from the second visit of the ROAD study who had completed assessment of handgrip strength, gait speed, and skeletal muscle mass measured by bioimpedance analysis. Presence of sarcopenia was determined according to the EWGSOP algorithm. Information collected included exercise habits in middle age. Results: Prevalence of sarcopenia was 13.8 % in men and 12.4 % in women, and tended to be significantly higher according to increasing age in both sexes. Factors associated with sarcopenia, as determined by logistic regression analysis, were chair stand time (odds ratio [OR], 1.09; 95 % confidence interval [CI], 1.04-1.14), one-leg standing time (OR, 0.97; 95 % CI, 0.96-0.99), and exercise habit in middle age (OR, 0.53; 95 % CI, 0.31-0.90). Exercise habit in middle age was associated with low prevalence of sarcopenia in older age. Furthermore, linear regression analysis revealed that exercise habits in middle age were significantly associated with grip strength (P <.001), gait speed (P <.001), and one-leg standing time (P =.005) in older age. Conclusions: This cross-sectional study suggests that exercise habit in middle age is a protective factor against sarcopenia in older age and effective in maintaining muscle strength and physical performance in older age. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation. Source

Urakami Y.,National Rehabilitation Center for Persons with Disabilities
Recent Patents on Medical Imaging

It has become feasible to study several aspects of consciousness because of recent progress in the neuroscience of perception, memory, and action, and advances in techniques of neuroimaging of human brain function. Consciousness has 2 main components: level of arousal (wakefulness) and content of consciousness (self awareness). Level of arousal has been investigated with electric correlates and structures in the brainstem and diencephalons that regulate the sleepwake cycle. From a behavioral and neurobiological perspective, sleep and consciousness are intimately connected. Recent functional brain imaging has been used in humans to investigate the neural mechanisms underlying the generation of sleep stages. Sleep consolidates new memories, and spindle activity is associated with improvements in procedural and declarative memory. The sleeping brain processes external information and detects the pertinence of its context. A default mode of brain function may explain consistent decreases in brain-activity during cognitive processing as compared to a passive resting state. The recent advances in neuroimaging, including functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) are reviewed with a focus on the possibility of prognostic tools to evaluate consciousness disturbance such as coma. Also recent advances in functional brain imaging and combined methods of electroencephalogram and magnetoencephalogram and/or fMRI, are reviewed with a focus on the progress on the evaluation of normal sleep physiology. Patents as neuroimaging tools in this field are introduced. © 2013 Bentham Science Publishers Source

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