Augmented Visual Feedback for Complex Motor Skill Acquisition: A Demonstration with Healthy Young Adults.

Mirror therapy (MT) is a treatment for improving motor function after stroke. Video therapy (VT) training combines observation and imitation of video clips, and it has been used to conduct efficient occupational therapy. We sought to determine the effects of MT and VT on tool-use with healthy young adults. We assigned participants to three different training groups in which they used their non-dominant left hands to move a ball with chopsticks: (a) a self-paced MT group (N = 14), (b) an MT group who moved the ball while looking at the mirror image of the right hand with a sound cue (4-second intervals) (N = 12), and (c) a group who imitated a video demonstration (4-second intervals) (N = 13). The ball-moving time was significantly reduced after training in all three groups: MT group (p < .001), MT-R group (p = .010), and VT group (p = .014), but the video group showed significantly greater relative improvements in motion variability (p = .030) and object prediction (p = .008).We concluded that MT was as effective as VT in improving movement speed, but, with these healthy young adults, MT was less effective than VT in learning speed control or hand pre-shaping to refine task movements for tool use.

GroEL Secreted from Bacillus subtilis Natto Exerted a Crucial Role for Anti-Inflammatory IL-10 Induction in THP-1 Cells.

Although diverse immunomodulatory reactions of probiotic bacteria have been reported, this effect via Bacillus subtilis natto remains unclear, despite its long consumption history in Japan and usage in Natto production. Hence, we performed a comparative analysis of the immunomodulatory activities of 23 types of B. subtilis natto isolated from Natto products to elucidate the key active components. Among the isolated 23 strains, the supernatant from B. subtilis strain 1 fermented medium showed the highest induction of anti-inflammatory IL-10 and pro-inflammatory IL-12 in THP-1 dendritic cells (THP-1 DC) after co-incubation. We isolated the active component from strain 1 cultured medium and employed DEAE-Sepharose chromatography with 0.5 M NaCl elution for fractionation. IL-10-inducing activity was specific to an approximately 60 kDa protein, GroEL, which was identified as a chaperone protein and was significantly reduced with anti-GroEL antibody. Differential expression analysis of strains 1 and 15, which had the lowest cytokine-producing activity, showed a higher expression of various genes involved in chaperones and sporulation in strain 1. Furthermore, GroEL production was induced in spore-forming medium. The present study is the first to show that the chaperone protein GroEL, secreted by B. subtilis natto during sporulation, plays a crucial role in IL-10 and IL-12 production in THP-1 DC.

Design, synthesis and evaluation of unnatural peptides as T1R2/T1R3 PAMs.

The sweet receptor T1R2/T1R3 is a member of G protein-coupled receptor family and recognizes diverse natural and synthetic sweeteners. Previously, we reported a novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 comprising an unnatural tripeptide structure. We classified the structure of these PAMs into three parts: "head", "linker" and "tail". Here, we report the design, synthesis and evaluation of various tail structures to obtain highly active unnatural peptide structure of PAM. In conclusion, we discovered the novel unnatural tetrapeptide with highly potent PAM activity on T1R2/T1R3 in a cell-based assay system.

Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3.

T1R2/T1R3 belongs to G protein coupled receptors, which recognizes diverse natural and synthetic sweeteners. A novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 was identified through high-throughput screening campaign. Comparing the structure of the potent compound with previously known PAM, we classified the structure of known PAM into three parts, defined as "head", "linker", and "tail". We then investigated the linker-tail structure. It was suggested by molecular docking models of T1R2/T1R3 that an amine that we introduced in the tail was the key for interaction with the receptor binding pocket. We thus synthesized various molecules and found unnatural tripeptide-PAMs, which potently enhance the sweetness of sucrose in sensory evaluation tests.

UV-sensitive photoreceptor protein OPN5 in humans and mice.

A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (λmax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (λmax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears. Most of these OPN5-immuno-reactivities in mice were co-localized with positive signals for the alpha-subunit of Gi. These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues.