219 research outputs found

    p59fyn is associated with the development of hepatic steatosis due to chronic ethanol consumption

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    p59fyn, a protein tyrosine kinase belonging to the src-family, is involved in the regulatory mechanism of acute response to ethanol in the central nervous system. A previous report showed an association between src-family kinase activity and fatty acid oxidation, and it also reported that hepatic free fatty acid levels were low in Fyn−/− mice. We examined, using Fyn−/− mice whether Fyn is also involved in fatty acid metabolism and the development of pathological changes in the liver in response to chronic ethanol consumption. C57BL/6J Fyn−/− and Fyn+/+ mice were fed for 8 weeks with either a liquid diet comprising ethanol or one in which the calories from ethanol were replaced with carbohydrates. Chronic ethanol consumption for 8 weeks resulted in remarkable hepatic steatosis in Fyn+/+ mice but not in Fyn−/− mice. Chronic ethanol consumption induced a significant decrease in hepatic FFA and triglyceride levels in Fyn−/− mice. Levels of interleukin-6, which is associated with the enhancement of fatty acid oxidation, was also increased significantly in the livers of ethanol-fed Fyn−/− mice. The results suggest that Fyn is involved in the enhancement of fatty acid oxidation and the development of hepatic steatosis caused by chronic ethanol consumption

    In Vivo Safety and Persistence of Endoribonuclease Gene-Transduced CD4+ T Cells in Cynomolgus Macaques for HIV-1 Gene Therapy Model

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    BACKGROUND: MazF is an endoribonuclease encoded by Escherichia coli that specifically cleaves the ACA sequence of mRNA. In our previous report, conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes resistant to HIV-1 replication. In this study, we examined the in vivo safety and persistence of MazF-transduced cynomolgus macaque CD4+ T cells infused into autologous monkeys. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo persistence of the gene-modified CD4+ T cells in the peripheral blood was monitored for more than half a year using quantitative real-time PCR and flow cytometry, followed by experimental autopsy in order to examine the safety and distribution pattern of the infused cells in several organs. Although the levels of the MazF-transduced CD4+ T cells gradually decreased in the peripheral blood, they were clearly detected throughout the experimental period. Moreover, the infused cells were detected in the distal lymphoid tissues, such as several lymph nodes and the spleen. Histopathological analyses of tissues revealed that there were no lesions related to the infused gene modified cells. Antibodies against MazF were not detected. These data suggest the safety and the low immunogenicity of MazF-transduced CD4+ T cells. Finally, gene modified cells harvested from the monkey more than half a year post-infusion suppressed the replication of SHIV 89.6P. CONCLUSIONS/SIGNIFICANCE: The long-term persistence, safety and continuous HIV replication resistance of the mazF gene-modified CD4+ T cells in the non-human primate model suggests that autologous transplantation of mazF gene-modified cells is an attractive strategy for HIV gene therapy

    Magnetostriction studies up to megagauss fields using fiber Bragg grating technique

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    We here report magnetostriction measurements under pulsed megagauss fields using a high-speed 100 MHz strain monitoring system devised using fiber Bragg grating (FBG) technique with optical filter method. The optical filter method is a detection scheme of the strain of FBG, where the changing Bragg wavelength of the FBG reflection is converted to the intensity of reflected light to enable the 100 MHz measurement. In order to show the usefulness and reliability of the method, we report the measurements for solid oxygen, spin-controlled crystal, and volborthite, a deformed Kagom\'{e} quantum spin lattice, using static magnetic fields up to 7 T and non-destructive millisecond pulse magnets up to 50 T. Then, we show the application of the method for the magnetostriction measurements of CaV4_{4}O9_{9}, a two-dimensional antiferromagnet with spin-halves, and LaCoO3_{3}, an anomalous spin-crossover oxide, in the megagauss fields.Comment: 9pages, 6 figures, Conference proceedings for MegaGauss16 at Kashiwa, Japan in Sept. 201

    Motivation of UK graduate students in education: Self-compassion moderates pathway from extrinsic motivation to intrinsic motivation

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    Academic motivation is recognised as a key factor for academic success and wellbeing. Highly motivated students actively engage with academic activities and maintain higher levels of wellbeing. Despite the importance of motivation in education, its relationship with engagement and wellbeing remains to be evaluated. Accordingly, this study explored the relationships between motivation, engagement, self-criticism and selfcompassion among UK education postgraduate students. Of 120 postgraduate students approached, 109 completed three self-report scales regarding those constructs. Correlation, regression and moderation analyses were performed. Intrinsic and extrinsic motivation were positively associated with engagement, whereas amotivation was negatively associated with it. Engagement positively predicted intrinsic motivation. Self-criticism and self-compassion moderated the pathway from extrinsic motivation to intrinsic motivation: higher self-criticism weakened the pathway, while higher selfcompassion strengthened it. Findings suggest the importance of engagement in relation to cultivating intrinsic motivation of education students. Moreover, enhancing selfcompassion and reducing self-criticism can help transfer extrinsic to intrinsic motivation.N/

    Genetic Variation in Quercus acutissima Carruth., in Traditional Japanese Rural Forests and Agricultural Landscapes, Revealed by Chloroplast Microsatellite Markers

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    uercus acutissima Carruth. is an economically important species that has long been cultivated in Japan, so is a valuable subject for investigating the impact of human activities on genetic variation in trees. In total, 2152 samples from 18 naturally regenerated populations and 28 planted populations in Japan and 13 populations from the northeastern part of Eurasia, near Japan, were analyzed using six maternally inherited chloroplast (cpDNA) simple sequence repeat (SSR) markers. Although 23 haplotypes were detected in total, both the Japanese natural and artificial populations exhibited much lower genetic diversity than the continental populations. The level of genetic differentiation among natural populations in Japan was also much lower (G’ST = 0.261) than that on the continent (G’ST = 0.856). These results suggest that human activities, such as historical seed transfer, have reduced genetic diversity within and among populations and resulted in a homogeneous genetic structure in Japan. The genetic characteristics of natural and artificial populations of Quercus acutissima in Japan are almost the same and it is likely that most of the natural populations are thought to have originated from individuals that escaped from plantations

    Self-compassion in Irish social work students: Relationships between resilience, engagement and motivation

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    Self-compassion recognises a meaning of life's suffering, aligning with existential positive psy-chology. Although this construct is known to protect our mental health, how to augment self-compassion remains to be evaluated. Social work students suffer from high rates of mental health problems, however research into self-compassion in this population remains to be devel-oped. This study aimed to evaluate i) relationships between self-compassion and more tradition-al positive constructs—resilience, engagement and motivation, and ii) differences of these con-structs between the levels of studies, to inform how self-compassion can be enhanced in social work students. One hundred twenty-nine Irish social work students completed self-report scales regarding self-compassion, resilience, engagement and motivation. Correlation, regression, and one-way MANOVA were conducted. Self-compassion was associated with gender, age, resili-ence, engagement and intrinsic motivation. Resilience and intrinsic motivation were significant predictors of self-compassion. There was no significant difference in the levels of these constructs between the levels of studies. Findings suggest that social work educators across different levels can strengthen students’ resilience and intrinsic motivation to cultivate the students' self-compassion. Moreover, the close relationships between self-compassion, resilience and in-trinsic motivation indicate that orienting students to a meaning of the studies helps their mental health.N/

    p53 Expression in Pretreatment Specimen Predicts Response to Neoadjuvant Chemotherapy Including Anthracycline and Taxane in Patients with Primary Breast Cancer.

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    While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p=0.045) and histological grade 3 (p=0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC
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