208 research outputs found

    Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation in vertebrates.

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    As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here, we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near centrosomes, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism

    Zolpidem Activation of Alpha 1-Containing GABAA Receptors Selectively Inhibits High Frequency Action Potential Firing of Cortical Neurons

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    Introduction: High frequency neuronal activity in the cerebral cortex can be induced by noxious stimulation during surgery, brain injury or poisoning. In this scenario, it is essential to block cortical hyperactivity to protect the brain against damage, e.g., by using drugs that act as positive allosteric modulators at GABAA receptors. Yet, cortical neurons express multiple, functionally distinct GABAA receptor subtypes. Currently there is a lack of knowledge which GABAA receptor subtypes would be a good pharmacological target to reduce extensive cortical activity.Methods: Spontaneous action potential activity was monitored by performing extracellular recordings from organotypic neocortical slice cultures of wild type and GABAAR-α1(H101R) mutant mice. Phases of high neuronal activity were characterized using peri-event time histograms. Drug effects on within-up state firing rates were quantified via Hedges’ g.Results: We quantified the effects of zolpidem, a positive modulator of GABAA receptors harboring α1-subunits, and the experimental benzodiazepine SH-053-2′F-S-CH3, which preferably acts at α2/3/5- but spares α1-subunits. Both agents decreased spontaneous action potential activity but altered the firing patterns in different ways. Zolpidem reduced action potential firing during highly active network states. This action was abolished by flumazenil, suggesting that it was mediated by benzodiazepine-sensitive GABAA receptors. SH-053-2′F-S-CH3 also attenuated neuronal activity, but unlike zolpidem, failed to reduce high frequency firing. To confirm that zolpidem actions were indeed mediated via α1-dependent actions, it was evaluated in slices from wild type and α(H101R) knock-in mice. Inhibition of high frequency action potential firing was observed in slices from wild type but not mutant mice.Conclusion: Our results suggest that during episodes of scarce and high neuronal activity action potential firing of cortical neurons is controlled by different GABAA receptor subtypes. Exaggerated firing of cortical neurons is reduced by positive modulation of α1-, but not α2/3/5-subunit containing GABAA receptors

    Large bubble rupture sparks fast liquid jet

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    This Letter presents the novel experimental observation of long and narrow jets shooting out in disconnecting large elongated bubbles. We investigate this phenomenon by carrying out experiments with various viscosities, surface tensions, densities and nozzle radii. We propose a universal scaling law for the jet velocity, which unexpectedly involves the bubble height to the power 3/2. This anomalous exponent suggests an energy focusing phenomenon. We demonstrate experimentally that this focusing is purely gravity-driven and independent of the pinch-off singularity

    Summary Report of the INL-JISEA Workshop on Nuclear Hybrid Energy Systems

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    The Institute for Nuclear Energy Science and Technology (INEST) and the Joint Institute for Strategic Energy Analysis (JISEA) co-sponsored an international workshop to identify research topics important in advancing the potential use of hybrid systems with a specific focus on nuclear-renewable hybrid systems. The workshop included presentations ranging from energy challenges and research and development directions being pursued by nations to multiple options for hybrid systems. Those options include one that is being commercialized to other opportunities and analysis results quantifying them. The workshop also involved two breakout sessions--one focused on thermal energy management issues especially at unit-operation scale and the second focused on system operations issues including system controls, regulatory issues, technical and economic analysis, and market challenges. A discussion involving the full group focused on more general issues such as societal involvement and participation. Key criteria for selecting hybrid energy system projects and metrics for comparing them were also identified by the full group

    It's Harder to Splash on Soft Solids

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    Droplets splash when they impact dry, flat substrates above a critical velocity that depends on parameters such as droplet size, viscosity and air pressure. By imaging ethanol drops impacting silicone gels of different stiffnesses we show that substrate stiffness also affects the splashing threshold. Splashing is reduced or even eliminated: droplets on the softest substrates need over 70\% more kinetic energy to splash than they do on rigid substrates. We show that this is due to energy losses caused by deformations of soft substrates during the first few microseconds of impact. We find that solids with Young's moduli 100\lesssim 100kPa reduce splashing, in agreement with simple scaling arguments. Thus materials like soft gels and elastomers can be used as simple coatings for effective splash prevention. Soft substrates also serve as a useful system for testing splash-formation theories and sheet-ejection mechanisms, as they allow the characteristics of ejection sheets to be controlled independently of the bulk impact dynamics of droplets.Comment: 5 pages, 4 figure
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