1,941 research outputs found

    Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR

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    Vibrio cholerae encodes six resistance-nodulation-division (RND) efflux systems which function in antimicrobial resistance, virulence factor production, and intestinal colonization. Among the six RND efflux systems, VexAB exhibited broad substrate specificity and played a predominant role in intrinsic antimicrobial resistance. The VexAB system was encoded in an apparent three gene operon that included vexR; which encodes an uncharacterized TetR family regulator. In this work we examined the role of vexR in vexRAB expression. We found that VexR bound to the vexRAB promoter and vexR deletion resulted in decreased vexRAB expression and increased susceptibility to VexAB antimicrobial substrates. Sub-strate-dependent induction of vexRAB was dependent on vexR and episomal vexR expression provided a growth advantage in the presence of the VexAB substrate deoxycholate. The expression of vexRAB increased, in a vexR-dependent manner, in response to the loss of RND efflux activity. This suggested that VexAB may function to export intracellular metabolites. Support for this hypothesis was provided by data showing that vexRAB was upregulated in several metabolic mutants including tryptophan biosynthetic mutants that were predicted to accumulate indole. In addition, vexRAB was found to be upregulated in response to exogenous indole and to contribute to indole resistance. The collective results indicate that vexR is required for vexRAB expression in response to VexAB substrates and that the VexAB RND efflux system modulates the intracellular levels of metabolites that could otherwise accumulate to toxic levels

    Apneusis responding to buspirone in multiple sclerosis

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    Apneusis is a disturbance of respiratory rhythm characterized by severely prolonged inspiratory effort, and is caused by bilateral lesions in the dorsal pons. In humans it is most commonly caused by pontine infarction and has rarely been reported in multiple sclerosis (MS). Here we report on a patient with MS who developed episodic apneusis which responded to treatment with buspirone, a serotonin type 1A receptor agonist

    Enhanced reaction kinetics in biological cells

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    The cell cytoskeleton is a striking example of "active" medium driven out-of-equilibrium by ATP hydrolysis. Such activity has been shown recently to have a spectacular impact on the mechanical and rheological properties of the cellular medium, as well as on its transport properties : a generic tracer particle freely diffuses as in a standard equilibrium medium, but also intermittently binds with random interaction times to motor proteins, which perform active ballistic excursions along cytoskeletal filaments. Here, we propose for the first time an analytical model of transport limited reactions in active media, and show quantitatively how active transport can enhance reactivity for large enough tracers like vesicles. We derive analytically the average interaction time with motor proteins which optimizes the reaction rate, and reveal remarkable universal features of the optimal configuration. We discuss why active transport may be beneficial in various biological examples: cell cytoskeleton, membranes and lamellipodia, and tubular structures like axons.Comment: 10 pages, 2 figure

    Electromechanical analysis of an adaptive piezoelectric energy harvester controlled by two segmented electrodes with shunt circuit networks

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    This paper presents an adaptive power harvester using a shunted piezoelectric control system with segmented electrodes. This technique has spurred new capability for widening the three simultaneous resonance frequency peaks using only a single piezoelectric laminated beam where normally previous works only provide a single peak for the resonance at the first mode. The benefit of the proposed techniques is that it provides effective and robust broadband power generation for application in self-powered wireless sensor devices. The smart structure beam with proof mass offset is considered to have simultaneous combination between vibration-based power harvesting and shunt circuit control-based electrode segments. As a result, the system spurs new development of the two mathematical methods using electromechanical closed-boundary value techniques and Ritz method-based weak-form analytical approach. The two methods have been used for comparison giving accurate results. For different electrode lengths using certain parametric tuning and harvesting circuit systems, the technique enables the prediction of the power harvesting that can be further proved to identify the performance of the system using the effect of varying circuit parameters so as to visualize the frequency and time waveform responses

    The Nucleoside Diphosphate Kinase Gene Nme3 Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance

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    The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (>95%) from heterozygous (t/+) males to their offspring. This phenotype is termed transmission ratio distortion (TRD) and is caused by the interaction of the t-complex responder (Tcr) with several quantitative trait loci (QTL), the t-complex distorters (Tcd1 to Tcd4), all located within the t-haplotype region. Current data suggest that the distorters collectively impair motility of all sperm derived from t/+ males; t-sperm is rescued by the responder, whereas +-sperm remains partially dysfunctional. Recently we have identified two distorters as regulators of RHO small G proteins. Here we show that the nucleoside diphosphate kinase gene Nme3 acts as a QTL on TRD. Reduction of the Nme3 dosage by gene targeting of the wild-type allele enhanced the transmission rate of the t-haplotype and phenocopied distorter function. Genetic and biochemical analysis showed that the t-allele of Nme3 harbors a mutation (P89S) that compromises enzymatic activity of the protein and genetically acts as a hypomorph. Transgenic overexpression of the Nme3 t-allele reduced t-haplotype transmission, proving it to be a distorter. We propose that the NME3 protein interacts with RHO signaling cascades to impair sperm motility through hyperactivation of SMOK, the wild-type form of the responder. This deleterious effect of the distorters is counter-balanced by the responder, SMOKTcr, a dominant-negative protein kinase exclusively expressed in t-sperm, thus permitting selfish behaviour and preferential transmission of the t-haplotype. In addition, the previously reported association of NME family members with RHO signaling in somatic cell motility and metastasis, in conjunction with our data involving RHO signaling in sperm motility, suggests a functional conservation between mechanisms for motility control in somatic cells and spermatozoa

    Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

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    <div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

    Global Development and Climate Change: A Game Theory Approach

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    The increasing concern with climate change is one of the main issues of our time, and thus we aim to theoretically and mathematically analyse its causes. However our approach follows a different stream of thought, presenting the reasoning and decision-making processes between technical and moral solutions. We have resorted to game theory models in order to demonstrate cooperative and non-cooperative scenarios, ranging from the traditional to the evolutionary within game theory. In doing so we are able to glimpse the development of modern society and a paradigm shift regarding human control over nature and to what extent it is harmful to the sustainability of our environment and the survival of future generations. Merging different fields of knowledge, we present a theoretical-philosophical approach, combined with empirical-mathematical solutions taking into account the agent-based behaviour guided blindly by instrumental rationality
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