Blockade of Gap Junction Hemichannel Suppresses Disease Progression in Mouse Models of Amyotrophic Lateral Sclerosis and Alzheimer's Disease

Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases.In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model.Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various neurodegenerative diseases

Investigating the Influence of Stiffness on Decision Making for Haptic Interface Evaluation Development

<p align="justify">Sensation input very important information for human life. In order to explore the mechanism of perception caused by compliance (hardness or softness), it is necessary to collect and examine the phenomena that occur along the way, including physical reactions. The goal of our study is to investigate whether social perception and behavior are influenced by the sensation of a human finger using the haptic interface device. In this paper as the pretest of a haptic interface device, psychological experiments whether touching softball or hardball is influence on social perception and behavior of people are duplicated. STUDY1 using only the index finger showed that information of a reaction force acted on a human finger has no influence on others impression and has influence on social behavior.  In STUDY2 with grasping the ball while collecting the surface electromyogram signals of the skin using sEMG sensors, the grasping ball's stiffness had influence on others impression and social behavior. This knowledge could be expected as a fundamental technology that improves the ease of use of a haptic interface and enables remote exchange of sensory information. </p&gt

Iterative learning control with sampled-data feedback for robot manipulators

This paper deals with the improvement of the stability of sampled-data (SD) feedback control for nonlinear multiple-input multiple-output time varying systems, such as robotic manipulators, by incorporating an off-line model based nonlinear iterative learning controller. The proposed scheme of nonlinear iterative learning control (NILC) with SD feedback is applicable to a large class of robots because the sampled-data feedback is required for model based feedback controllers, especially for robotic manipulators with complicated dynamics (6 or 7 DOF, or more), while the feedforward control from the off-line iterative learning controller should be assumed as a continuous one. The robustness and convergence of the proposed NILC law with SD feedback is proven, and the derived sufficient condition for convergence is the same as the condition for a NILC with a continuous feedback control input. With respect to the presented NILC algorithm applied to a virtual PUMA 560 robot, simulation results are presented in order to verify convergence and applicability of the proposed learning controller with SD feedback controller attache

Virtual Teaching Based on Hand Manipulability for Multi-Fingered Robots

A virtual robot teaching that consists of human demonstration and motion-intention analysis in a virtual reality environment is an advanced technology of automatic programming for multi-fingered robots. As the type of virtual hand model displayed on-screen, a human-hand model is better than a robot-hand model in terms of teaching time and a stable manipulation of virtual object. However it may occurs that robot cannot grasp an object at a teaching position and orientation of the robot hand because a geometrical size and motional function of the robot hand is not same as that of the human hand. To solve this problem, we propose a virtual teaching based on hand manipulability, in which a position and orientation of the robot hand is determined so as to maximize a manipulability of the robot hand on the condition that the robot grasps the object at the teaching contact points on the object. Experimental results of a pick-and-place task are shown to demonstrate the effectiveness of the proposed method

Physical, behavioral, and hormonal changes in the resumption of sexual receptivity during postpartum infertility in female bonobos at Wamba

The operational sex ratio (OSR) is used as a predictor for the intensity of mating competition. While many factors affect the OSR, there tends to be a high male bias in primate species with long interbirth intervals and non-seasonal breeding, such as hominid apes. However, the OSR of bonobos (Pan paniscus) is lower than that of chimpanzees (Pan troglodytes), which is thought to reduce competitive and aggressive male behaviors. The low OSR of bonobos is considered to result from the early resumption of female sexual receptivity during postpartum infertility and the receptivity that they continue to show until the late stage of pregnancy. In this study, we aimed to examine the early resumption of sexual receptivity by providing quantitative data on the resumption of maximal swelling (MS) in sexual skin and copulation, and changes in urinary estrone conjugate (E1C) concentrations during postpartum infertility in wild bonobos at Wamba in the Luo Scientific Reserve, Democratic Republic of the Congo. An analysis of 9 years of data revealed that females showed the first MS at 225.4 +/- 132.7 days after parturition and performed the first copulation at 186.8 +/- 137.5 days after parturition, both of which were in the early stage of postpartum infertility. The proportion of days with MS and the frequency of copulation steadily increased subsequently; however, the rate of increase gradually slowed approximately 42-48 months after parturition. There was a significant correlation between the proportion of days with MS and the frequency of copulation in each period for each female. We confirmed that E1C concentrations were significantly higher during the MS phase than during the non-MS phase. Data collected over 15 months on the E1C concentration during MS showed that it increased linearly from the early stage of lactation to the next conception. These results suggest that, although female bonobos do not usually conceive until 49.7 months after parturition, they resume MS and receptivity at a low level of E1C concentration during an early stage of postpartum infertility. This study of female bonobo receptivity and sex hormone changes during the postpartum non-fertile period provides important insights for examining the evolution of low OSR, which has been considered to contribute to peaceful social relationships among bonobos