14,975 research outputs found

    Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons.

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    Previous studies have revealed a critical role for CREB-regulated transcriptional coactivator (CRTC1) in regulating neuronal gene expression during learning and memory. CRTC1 localizes to synapses but undergoes activity-dependent nuclear translocation to regulate the transcription of CREB target genes. Here we investigate the long-distance retrograde transport of CRTC1 in hippocampal neurons. We show that local elevations in calcium, triggered by activation of glutamate receptors and L-type voltage-gated calcium channels, initiate active, dynein-mediated retrograde transport of CRTC1 along microtubules. We identify a nuclear localization signal within CRTC1, and characterize three conserved serine residues whose dephosphorylation is required for nuclear import. Domain analysis reveals that the amino-terminal third of CRTC1 contains all of the signals required for regulated nucleocytoplasmic trafficking. We fuse this region to Dendra2 to generate a reporter construct and perform live-cell imaging coupled with local uncaging of glutamate and photoconversion to characterize the dynamics of stimulus-induced retrograde transport and nuclear accumulation

    Hard x-ray polarimetry with the Ramaty High Energy Solar Spectroscopic Imager (RHESSI)

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    Although designed primarily as a hard X-ray imager and spectrometer, the Ramaty High Energy Solar Spectroscopic Imager (RHESSI) is also capable of measuring the polarization of hard X-rays (20-100 keV) from solar flares. This capability arises from the inclusion of a small unobstructed Be scattering element that is strategically located within the cryostat that houses the array of nine germanium detectors. The Ge detectors are segmented, with both a front and rear active volume. Low energy photons (below about 100 keV) can reach a rear segment of a Ge detector only indirectly, by scattering. Low energy photons from the Sun have a direct path to the Be and have a high probability of Compton scattering into a rear segment of a Ge detector. The azimuthal distribution of these scattered photons carries with it a signature of the linear polarization of the incident flux. Sensitivity estimates, based on simulations and in-flight background measurements, indicate that a 20-100 keV polarization sensitivity of less than a few percent can be achieved for X-class flares

    Solid-state metathesis reactions under pressure: A rapid route to crystalline gallium nitride

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    High pressure chemistry has traditionally involved applying pressure and increasing temperature until conditions become thermodynamically favorable for phase transitions or reactions to occur. Here, high pressure alone is used as a starting point for carrying out rapid, self-propagating metathesis reactions. By initiating chemical reactions under pressure, crystalline phases, such as gallium nitride, can be synthesized which are inaccessible when initiated from ambient conditions. The single-phase gallium nitride made by metathesis reactions under pressure displays significant photoluminescence intensity in the blue/ultraviolet region. The absence of size or surface-state effects in the photoluminescence spectra show that the crystallites are of micron dimensions. The narrow lines of the x-ray diffraction patterns and scanning electron microscopy confirm this conclusion. Brightly luminescent thin films can be readily grown using pulsed laser deposition

    Electricity consumption and household characteristics: Implications for census-taking in a smart metered future

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    This paper assesses the feasibility of determining key household characteristics based on temporal load profiles of household electricity demand. It is known that household characteristics, behaviours and routines drive a number of features of household electricity loads in ways which are currently not fully understood. The roll out of domestic smart meters in the UK and elsewhere could enable better understanding through the collection of high temporal resolution electricity monitoring data at the household level. Such data affords tremendous potential to invert the established relationship between household characteristics and temporal load profiles. Rather than use household characteristics as a predictor of loads, observed electricity load profiles, or indicators based on them, could instead be used to impute household characteristics. These micro level imputed characteristics could then be aggregated at the small area level to produce ‘census-like’ small area indicators. This work briefly reviews the nature of current and future census taking in the UK before outlining the household characteristics that are to be found in the UK census and which are also known to influence electricity load profiles. It then presents descriptive analysis of two smart meter-like datasets of half-hourly domestic electricity consumption before reporting on the results from a multilevel modelling-based analysis of the same data. The work concludes that a number of household characteristics of the kind to be found in UK census-derived small area statistics may be predicted from particular load profile indicators. A discussion of the steps required to test and validate this approach and the wider implications for census taking is also provided

    In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel Dense Granule Proteins Important for Parasite Growth and Pathogenesis.

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    UnlabelledToxoplasma gondii is an obligate intracellular parasite that invades host cells and replicates within a unique parasitophorous vacuole. To maintain this intracellular niche, the parasite secretes an array of dense granule proteins (GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the parasite is replicating within the host cell. Despite the central role of GRAs in the Toxoplasma life cycle, only a subset of these proteins have been identified, and many of their roles have not been fully elucidated. In this report, we utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted into the vacuole and then identify those proteins by affinity purification and mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a large number of known and candidate GRAs and verified localization of 13 novel GRA proteins by endogenous gene tagging. We proceeded to functionally characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene knockout. While Δgra38 and Δgra40 parasites showed no altered phenotype, disruption of GRA39 results in slow-growing parasites that contain striking lipid deposits in the parasitophorous vacuole, suggesting a role in lipid regulation that is important for parasite growth. In addition, parasites lacking GRA39 showed dramatically reduced virulence and a lower tissue cyst burden in vivo Together, the findings from this work reveal a partial vacuolar proteome of T. gondii and identify a novel GRA that plays a key role in parasite replication and pathogenesis.ImportanceMost intracellular pathogens reside inside a membrane-bound vacuole within their host cell that is extensively modified by the pathogen to optimize intracellular growth and avoid host defenses. In Toxoplasma, this vacuole is modified by a host of secretory GRA proteins, many of which remain unidentified. Here we demonstrate that in vivo biotinylation of proximal and interacting proteins using the promiscuous biotin ligase BirA* is a powerful approach to rapidly identify vacuolar GRA proteins. We further demonstrate that one factor identified by this approach, GRA39, plays an important role in the ability of the parasite to replicate within its host cell and cause disease

    Cloud properties from the analysis of AVHRR observations for FIRE 2

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    Preliminary results are presented for cloud properties from the analysis of AVHRR observations for FIRE 2. The properties were obtained from a combination of the spatial coherence method and a multispectral retrieval scheme. Geographically gritted fields for the number of cloud layers were produced. For single layered cloud systems, fractional cloud cover, cloud emission temperature, cloud emissivity, and particle size were retrieved. Statistics on the properties of upper-level clouds and the Coffeeville cloud conditions are presented

    Characterization of Sol-Gel-Derived Cobalt Oxide Xerogels as Electrochemical Capacitors

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    Very fine cobalt oxide xerogel powders were prepared using a unique solution chemistry associated with the sol-gel process. The effect of thermal treatment on the surface area, pore volume, crystallinity, particle structure, and corresponding electrochemical properties of the resulting xerogels was investigated and found to have significant effects on all of these properties. The xerogel remained amorphous as Co(OH)2 up to 160°C, and exhibited maxima in both the surface area and pore volume at this temperature. With an increase in the temperature above 200°C, both the surface area and pore volume decreased sharply, because the amorphous Co(OH)2 decomposed to form CoO that was subsequently oxidized to form crystalline Co3O4. In addition, the changes in the surface area, pore volume, crystallinity, and particle structure all had significant but coupled effects on the electrochemical properties of the xerogels. A maximum capacitance of 291 F/g was obtained for an electrode prepared with the CoOx xerogel calcined at 150°C, which was consistent with the maxima exhibited in both the surface area and pore volume; this capacitance was attributed solely to a surface redox mechanism. The cycle life of this electrode was also very stable for many thousands of cycles

    The 8 o'clock Arc: A Serendipitous Discovery of a Strongly Lensed Lyman Break Galaxy in the SDSS DR4 Imaging Data

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    We report on the serendipitous discovery of the brightest Lyman Break Galaxy (LBG) currently known, a galaxy at z=2.73 that is being strongly lensed by the z=0.38 Luminous Red Galaxy (LRG) SDSS J002240.91+143110.4. The arc of this gravitational lens system, which we have dubbed the "8 o'clock arc" due to its time of discovery, was initially identified in the imaging data of the Sloan Digital Sky Survey Data Release 4 (SDSS DR4); followup observations on the Astrophysical Research Consortium (ARC) 3.5m telescope at Apache Point Observatory confirmed the lensing nature of this system and led to the identification of the arc's spectrum as that of an LBG. The arc has a spectrum and a redshift remarkably similar to those of the previous record-holder for brightest LBG (MS 1512-cB58, a.k.a "cB58"), but, with an estimated total magnitude of (g,r,i) = (20.0,19.2,19.0) and surface brightness of (mu_g,mu_r,mu_i) = (23.3, 22.5, 22.3) mag/arcsec^2, the 8 o'clock arc is thrice as bright. The 8 o'clock arc, which consists of three lensed images of the LBG, is 162deg (9.6arcsec) long and has a length-to-width ratio of 6:1. A fourth image of the LBG -- a counter-image -- can also be identified in the ARC 3.5m g-band images. A simple lens model for the system assuming a singular isothermal ellipsoid potential yields an Einstein radius of 2.91+/-0.14 arcsec, a total mass for the lensing LRG (within the (10.6+/-0.5)/h kpc enclosed by the lensed images) of 1.04x10^12/h Msun, and a magnification factor for the LBG of 12.3(+15/-3.6). The LBG itself is intrinsically quite luminous (approximately 6L*) and shows indications of massive recent star formation, perhaps as high as 160/h Msun/year.Comment: 4 pages 5 figures, submitted to ApJ Letter
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