583 research outputs found

    Nicotinamide is an Endogenous Agonist for a C. elegans TRPV OSM-9 and OCR-4 Channel

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    TRPV ion channels are directly activated by sensory stimuli and participate in thermo-, mechano- and chemo-sensation. They are also hypothesized to respond to endogenous agonists that would modulate sensory responses. Here, we show that the nicotinamide (NAM) form of vitamin B3 is an agonist of a Caenorhabditis elegans TRPV channel. Using heterologous expression in Xenopus oocytes, we demonstrate that NAM is a soluble agonist for a channel consisting of the well-studied OSM-9 TRPV subunit and relatively uncharacterized OCR-4 TRPV subunit as well as the orthologous Drosophila Nan-Iav TRPV channel, and we examine stoichiometry of subunit assembly. Finally, we show that behaviours mediated by these C. elegans and Drosophila channels are responsive to NAM, suggesting conservation of activity of this soluble endogenous metabolite on TRPV activity. Our results in combination with the role of NAM in NAD+ metabolism suggest an intriguing link between metabolic regulation and TRPV channel activity

    Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy

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    The pathogenesis of chemotherapy-induced peripheral neuropathy (CIPN) is poorly understood. Here, we report that the CIPN-causing drug bortezomib (Bort) promotes delta 2 tubulin (D2) accumulation while affecting microtubule stability and dynamics in sensory neurons in vitro and in vivo and that the accumulation of D2 is predominant in unmyelinated fibers and a hallmark of bortezomib-induced peripheral neuropathy (BIPN) in humans. Furthermore, while D2 overexpression was sufficient to cause axonopathy and inhibit mitochondria motility, reduction of D2 levels alleviated both axonal degeneration and the loss of mitochondria motility induced by Bort. Together, our data demonstrate that Bort, a compound structurally unrelated to tubulin poisons, affects the tubulin cytoskeleton in sensory neurons in vitro, in vivo, and in human tissue, indicating that the pathogenic mechanisms of seemingly unrelated CIPN drugs may converge on tubulin damage. The results reveal a previously unrecognized pathogenic role for D2 in BIPN that may occur through altered regulation of mitochondria motility

    Attractiveness of a Four-component Pheromone Blend to Male Navel Orangeworm Moths

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    The attractiveness to male navel orangeworm moth, Amyelois transitella, of various combinations of a four-component pheromone blend was measured in wind-tunnel bioassays. Upwind flight along the pheromone plume and landing on the odor source required the simultaneous presence of two components, (11Z,13Z)-hexadecadienal and (3Z,6Z,9Z,12Z,15Z)-tricosapentaene, and the addition of either (11Z,13Z)-hexadecadien-1-ol or (11Z,13E)-hexadecadien-1-ol. A mixture of all four components produced the highest levels of rapid source location and source contact. In wind-tunnel assays, males did not seem to distinguish among a wide range of ratios of any of the three components added to (11Z,13Z)-hexadecadienal. Dosages of 10 and 100 ng of the 4-component blend produced higher levels of source location than dosages of 1 and 1,000 ng

    Knowledge, experience, and potential risks of dating violence among Japanese university students: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>The Domestic Violence Prevention Act came into effect in Japan in 2001, but covers only marriage partner violence and post-divorce partner violence, and does not recognize intimate partner violence (IPV). The present study was performed to determine the experience of harassment, both toward and from an intimate partner, and recognition of harassment as IPV among Japanese university students.</p> <p>Methods</p> <p>A self-administered questionnaire survey regarding the experience of harassment involving an intimate partner was conducted as a cross-sectional study among freshman students in a prefectural capital city in Japan.</p> <p>Results</p> <p>A total of 274 students participated in the present study. About half of the subjects (both male and female students) had experience of at least one episode of harassment toward or had been the recipient of harassment from an intimate partner. However, the study participants did not recognize verbal harassment, controlling activities of an intimate partner, and unprotected sexual intercourse as violence. Experience of attending a lecture/seminar about domestic violence and dating violence did not contribute to appropriate help-seeking behavior.</p> <p>Conclusions</p> <p>An educational program regarding harassment and violence prevention and appropriate help-seeking behavior should be provided in early adolescence to avoid IPV among youth.</p

    The Brexit Botnet and User-Generated Hyperpartisan News

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    In this paper we uncover a network of Twitterbots comprising 13,493 accounts that tweeted the U.K. E.U. membership referendum, only to disappear from Twitter shortly after the ballot. We compare active users to this set of political bots with respect to temporal tweeting behavior, the size and speed of retweet cascades, and the composition of their retweet cascades (user-to-bot vs. bot-to-bot) to evidence strategies for bot deployment. Our results move forward the analysis of political bots by showing that Twitterbots can be effective at rapidly generating small to medium-sized cascades; that the retweeted content comprises user-generated hyperpartisan news, which is not strictly fake news, but whose shelf life is remarkably short; and, finally, that a botnet may be organized in specialized tiers or clusters dedicated to replicating either active users or content generated by other bots
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