Acute physical exercise increases reactive oxygen species in skeletal muscle, leading to tissue damage and fatigue. Molecular hydrogen (H2) acts as a therapeutic antioxidant directly or indirectly by inducing antioxidative enzymes. Here, we examined the effects of drinking H2 water (H2-infused water) on psychometric fatigue and endurance capacity in a randomized, double-blind, placebo-controlled fashion. In Experiment 1, all participants drank only placebo water in the first cycle ergometer exercise session, and for comparison they drank either H2 water or placebo water 30 min before exercise in the second examination. In these healthy non-trained participants (n = 99), psychometric fatigue judged by visual analogue scales was significantly decreased in the H2 group after mild exercise. When each group was divided into 2 subgroups, the subgroup with higher visual analogue scale values was more sensitive to the effect of H2. In Experiment 2, trained participants (n = 60) were subjected to moderate exercise by cycle ergometer in a similar way as in Experiment 1, but exercise was performed 10 min after drinking H2 water. Endurance and fatigue were significantly improved in the H2 group as judged by maximal oxygen consumption and Borg’s scale, respectively. Taken together, drinking H2 water just before exercise exhibited anti-fatigue and endurance effects.

Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors.

BackgroundColorectal cancer arises from the accumulation of genetic mutations that induce dysfunction of intracellular signaling. However, the underlying mechanism of colorectal tumorigenesis driven by genetic mutations remains yet to be elucidated.ResultsTo investigate colorectal tumorigenesis at a system-level, we have reconstructed a large-scale Boolean network model of the human signaling network by integrating previous experimental results on canonical signaling pathways related to proliferation, metastasis, and apoptosis. Throughout an extensive simulation analysis of the attractor landscape of the signaling network model, we found that the attractor landscape changes its shape by expanding the basin of attractors for abnormal proliferation and metastasis along with the accumulation of driver mutations. A further hypothetical study shows that restoration of a normal phenotype might be possible by reversely controlling the attractor landscape. Interestingly, the targets of approved anti-cancer drugs were highly enriched in the identified molecular targets for the reverse control.ConclusionsOur results show that the dynamical analysis of a signaling network based on attractor landscape is useful in acquiring a system-level understanding of tumorigenesis and developing a new therapeutic strategy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0341-9) contains supplementary material, which is available to authorized users.

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Abstract:In this paper we discuss the design and evaluation of a mobile based tool to collect activity data on a large scale. The current approach, based on an existing activity recognition module, recognizes class transitions from a set of specific activities (for example walking and running) to the standing still activity. Once this transition is detected the system prompts the user to provide a label for their previous activity. This label, along with the raw sensor data, is then stored locally prior to being uploaded to cloud storage. The system was evaluated by ten users. Three evaluation protocols were used, including a structured, semi-structured and free living protocol. Results indicate that the mobile application could be used to allow the user to provide accurate ground truth labels for their activity data. Similarities of up to 100% where observed when comparing the user prompted labels and those from an observer during structured lab based experiments. Further work will examine data segmentation and personalization issues in order to refine the system.

BackgroundHistone acetylation is regulated in response to stress and plays an important role in learning and memory. Chronic stress is known to deteriorate cognition, whereas acute stress facilitates memory formation. However, whether acute stress facilitates memory formation when it is applied after fear stimulation is not yet known. Therefore, this study aimed to investigate the effect of acute stress applied after fear training on memory formation, mRNA expression of brain-derived neurotrophic factor (BDNF), epigenetic regulation of BDNF expression, and corticosterone level in mice in vivo.MethodsMice were subjected to acute immobilization stress for 30 min at 60 or 90 min after contextual fear conditioning training, and acetylation of histone 3 at lysine 14 (H3K14) and level of corticosterone were measured using western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A freezing behavior test was performed 24 h after training, and mRNA expression of BDNF was measured using real-time polymerase chain reactions. Different groups of mice were used for each test.ResultsFreezing behavior significantly decreased with the down-regulation of BDNF mRNA expression caused by acute immobilization stress at 60 min after fear conditioning training owing to the reduction of H3K14 acetylation. However, BDNF mRNA expression and H3K14 acetylation were not reduced in animals subjected to immobilization stress at 90 min after the training. Further, the corticosterone level was significantly high in mice subjected to immobilization stress at 60 min after the training.ConclusionAcute immobilization stress for 30 min at 60 min after fear conditioning training impaired memory formation and reduced BDNF mRNA expression and H3K14 acetylation in the hippocampus of mice owing to the high level of corticosterone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12993-016-0092-1) contains supplementary material, which is available to authorized users.

We propose a selection procedure of principal components in principal component regression. Our method selects principal components using variable selection procedures instead of a small subset of major principal components in principal component regression. Our procedure consists of two steps to improve estimation and prediction. First, we reduce the number of principal components using the conventional principal component regression to yield the set of candidate principal components and then select principal components among the candidate set using sparse regression techniques. The performance of our proposals is demonstrated numerically and compared with the typical dimension reduction approaches (including principal component regression and partial least square regression) using synthetic and real datasets.

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