4,521 research outputs found

    Augmented Cocaine Seeking in Response to Stress or CRF Delivered into the Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated by CRF Receptor Type 1 But Not CRF Receptor Type 2

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    Stressful events are determinants of relapse in recovering cocaine addicts. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) regulation of neurocircuitry involved in drug seeking. We previously reported that the reinstatement of cocaine seeking by a stressor (footshock) is CRF dependent and is augmented in rats that self-administered cocaine under long-access (LgA; 6 h daily) conditions for 14 d when compared with rats provided shorter daily cocaine access [short access (ShA) rats; 2 h daily]. Further, we have demonstrated that reinstatement in response to intracerebroventricular CRF administration is heightened in LgA rats. This study examined the role of altered ventral tegmental area (VTA) responsiveness to CRF in intake-dependent increases in CRF- and stress-induced cocaine seeking. Bilateral intra-VTA administration of CRF (250 or 500 ng/side) produced reinstatement in LgA but not ShA rats. In LgA rats, intra-VTA CRF-induced reinstatement was blocked by administration of the CRF-receptor type 1 (CRF-R1) antagonist antalarmin (500 ng/side) or CP-376395 (500 ng/side), but not the CRF-R2 antagonist astressin-2B (500 ng or 1 ÎŒg/side) or antisauvagine-30(ASV-30; 500 ng/side) into the VTA. Likewise, intra-VTA antalarmin, but not astressin-2B, blocked footshock-induced reinstatement in LgA rats. By contrast, neither intra-VTA antalarmin nor CP-376395 altered food-reinforced lever pressing. Intra-VTA injection of the CRF-R1-selective agonist cortagine (100 ng/side) but not the CRF-R2-selective agonist rat urocortin II (rUCN II; 250 ng/side) produced reinstatement. These findings reveal that excessive cocaine use increases susceptibility to stressor-induced relapse in part by augmenting CRF-R1-dependent regulation of addiction-related neurocircuitry in the VTA

    Suspended nanochannel resonators at attogram precision

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    Nanomechanical resonators can quantify individual particles down to a single atom; however the applications are limited due to their degraded performance in solution. Suspended micro- and nanochannel resonators can achieve vacuum level performances for samples in solution since the target analyte flows through an integrated channel within the resonator. Here we report on a new generation suspended nanochannel resonator (SNR) that operates at approximately 2 MHz with quality factors between 10,000-20,000. The SNR is measured to have a mass sensitivity of 8.2 mHz/attogram. With an optimized oscillator system, we show that the resonator can be oscillated with a mass equivalent frequency stability of 0.85 attogram (4 parts-perbillion) at 1 kHz bandwidth, which is 1.8 times the calculated stability imposed by the thermal noise. We demonstrate the use of this mass resolution by quantifying the mass and concentration of nanoparticles down to 10 nm in solution

    Mechanisms of increased Trichodesmium fitness under iron and phosphorus co-limitation in the present and future ocean

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    © The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 12081, doi:10.1038/ncomms12081.Nitrogen fixation by cyanobacteria supplies critical bioavailable nitrogen to marine ecosystems worldwide; however, field and lab data have demonstrated it to be limited by iron, phosphorus and/or CO2. To address unknown future interactions among these factors, we grew the nitrogen-fixing cyanobacterium Trichodesmium for 1 year under Fe/P co-limitation following 7 years of both low and high CO2 selection. Fe/P co-limited cell lines demonstrated a complex cellular response including increased growth rates, broad proteome restructuring and cell size reductions relative to steady-state growth limited by either Fe or P alone. Fe/P co-limitation increased abundance of a protein containing a conserved domain previously implicated in cell size regulation, suggesting a similar role in Trichodesmium. Increased CO2 further induced nutrient-limited proteome shifts in widespread core metabolisms. Our results thus suggest that N2-fixing microbes may be significantly impacted by interactions between elevated CO2 and nutrient limitation, with broad implications for global biogeochemical cycles in the future ocean.Grant support was provided by U.S. National Science Foundation OCE 1260490 to D.A.H., E.A.W. and F.-X.F., and OCE OA 1220484 and G.B. Moore Foundation 3782 and 3934 to M.A.S

    Eulerian simulation of the fluid dynamics of helicopter brownout

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    A computational model is presented that can be used to simulate the development of the dust cloud that can be entrained into the air when a helicopter is operated close to the ground in desert or dusty conditions. The physics of this problem, and the associated pathological condition known as ‘brownout’ where the pilot loses situational awareness as a result of his vision being occluded by dust suspended in the flow around the helicopter, is acknowledged to be very complex. The approach advocated here involves an approximation to the full dynamics of the coupled particulate-air system. Away from the ground, the model assumes that the suspended particles remain in near equilibrium under the action of aerodynamic forces. Close to the ground, this model is replaced by an algebraic sublayer model for the saltation and entrainment process. The origin of the model in the statistical mechanics of a distribution of particles governed by aerodynamic forces allows the validity of the method to be evaluated in context by comparing the physical properties of the suspended particulates to the local properties of the flow field surrounding the helicopter. The model applies in the Eulerian frame of reference of most conventional Computational Fluid Dynamics codes and has been coupled with Brown’s Vorticity Transport Model. Verification of the predictions of the coupled model against experimental data for particulate entrainment and transport in the flow around a model rotor are encouraging. An application of the coupled model to analyzing the differences in the geometry and extent of the dust clouds that are produced by single main rotor and tandem-rotor configurations as they decelerate to land has shown that the location of the ground vortex and the size of any regions of recirculatory flow, should they exist, play a primary role in governing the extent of the dust cloud that is created by the helicopter

    TOI-150: A transiting hot Jupiter in the TESS southern CVZ

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    We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J},, R_{p}=1.38\pm0.04\ R_{J})orbitingamiddle−agedstar() orbiting a middle-aged star (\log g=4.152^{+0.030}_{-0.043})intheTransitingExoplanetSurveySatellite(TESS)southerncontinuousviewingzone() in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone (\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ
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