602 research outputs found

    Interphase Nucleo-Cytoplasmic Shuttling and Localization of SIRT2 during Mitosis

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    The human NAD+-dependent protein deacetylase SIRT2 resides predominantly in the cytoplasm where it functions as a tubulin deacetylase. Here we report that SIRT2 maintains a largely cytoplasmic localization during interphase by active nuclear export in a Crm1-dependent manner. We identified a functional, leptomycin B-sensitive, nuclear export signal sequence within SIRT2. During the cell cycle, SIRT2 becomes enriched in the nucleus and is associated with mitotic structures, beginning with the centrosome during prophase, the mitotic spindle during metaphase, and the midbody during cytokinesis. Cells overexpressing wild-type or a catalytically inactive SIRT2 exhibit an increase in multinucleated cells. The findings suggest a novel mechanism of regulating SIRT2 function by nucleo-cytoplasmic shuttling, as well as a role for SIRT2 in the nucleus during interphase and throughout mitosis

    Modelling Drosophila motion vision pathways for decoding the direction of translating objects against cluttered moving backgrounds

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    Decoding the direction of translating objects in front of cluttered moving backgrounds, accurately and efficiently, is still a challenging problem. In nature, lightweight and low-powered flying insects apply motion vision to detect a moving target in highly variable environments during flight, which are excellent paradigms to learn motion perception strategies. This paper investigates the fruit fly Drosophila motion vision pathways and presents computational modelling based on cuttingedge physiological researches. The proposed visual system model features bio-plausible ON and OFF pathways, wide-field horizontal-sensitive (HS) and vertical-sensitive (VS) systems. The main contributions of this research are on two aspects: (1) the proposed model articulates the forming of both direction-selective and direction-opponent responses, revealed as principalfeaturesofmotionperceptionneuralcircuits,inafeed-forwardmanner;(2)italsoshowsrobustdirectionselectivity to translating objects in front of cluttered moving backgrounds, via the modelling of spatiotemporal dynamics including combination of motion pre-filtering mechanisms and ensembles of local correlators inside both the ON and OFF pathways, which works effectively to suppress irrelevant background motion or distractors, and to improve the dynamic response. Accordingly, the direction of translating objects is decoded as global responses of both the HS and VS systems with positive ornegativeoutputindicatingpreferred-direction or null-direction translation.The experiments have verified the effectiveness of the proposed neural system model, and demonstrated its responsive preference to faster-moving, higher-contrast and larger-size targets embedded in cluttered moving backgrounds

    Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level

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    <p>Abstract</p> <p>Background</p> <p>Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats.</p> <p>Methods</p> <p>One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured.</p> <p>Results</p> <p>Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea.</p> <p>Conclusion</p> <p>These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.</p

    Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging-Related Transcriptional Networks

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    The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control. Sirt6 can interact with the stress-responsive transcription factor NF-κB and regulate some NF-κB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known. Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-α. More than half of Sirt6 target genes are only revealed upon stress-signaling. The majority of genes bound by NF-κB subunit RelA recruit Sirt6, and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner. Integrative analysis with global gene expression patterns in wild-type, Sirt6−/−, and double Sirt6−/− RelA−/− cells reveals the epistatic relationships between Sirt6 and RelA in shaping diverse temporal patterns of gene expression. Genes under the direct joint control of Sirt6 and RelA include several with prominent roles in cell senescence and organismal aging. These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-κB signaling in stress response and aging
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