4,303 research outputs found

    Dopamine-D1 and δ-opioid receptors co-exist in rat striatal neurons

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    Cocaine’s enhancement of dopaminergic neurotransmission in the mesolimbic pathway plays a critical role in the initial reinforcing properties of this drug. However, other neurotransmitter systems are also integral to the addiction process. A large body of data indicates that opioids and dopamine together mediate emotional and reinforced behaviors. In support of this, cocaine-mediated increases in activation of dopamine D1 receptors (D1R) results in a desensitization of δ-opioid receptor (DOR) signaling through adenylyl cyclase (AC) in striatal neurons. To further define cellular mechanisms underlying this effect, the subcellular distribution of DOR and D1R was examined in the rat dorsolateral striatum. Dual immunoperoxidase/gold-silver detection combined with electron microscopy was used to identify DOR and D1R immunoreactivities in the same section of tissue. Semi-quantitative analysis revealed that a subset of dendritic cellular profiles exhibited both DOR and D1R immunoreactivities. Of 165 randomly sampled D1R immunoreactive profiles, 43% contained DOR. Similarly of 198 DOR-labeled cellular profiles, 52% contained D1R. The present data provide ultrastructural evidence for co-existence between DOR and D1R in striatal neurons, suggesting a possible mechanism whereby D1R modulation may alter DOR function

    Melting of hexagonal skyrmion states in chiral magnets

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    Skyrmions are spiral structures observed in thin films of certain magnetic materials (Uchida et al 2006 Science 311 359–61). Of the phases allowed by the crystalline symmetries of these materials (Yi et al 2009 Phys. Rev. B 80 054416), only the hexagonally packed phases (SCh) have been observed. Here the melting of the SCh phase is investigated using Monte Carlo simulations. In addition to the usual measure of skyrmion density, chiral charge, a morphological measure is considered. In doing so it is shown that the low-temperature reduction in chiral charge is associated with a change in skyrmion profiles rather than skyrmion destruction. At higher temperatures, the loss of six-fold symmetry is associated with the appearance of elongated skyrmions that disrupt the hexagonal packing

    Non-structural protein-1 is required for West Nile virus replication complex formation and viral RNA synthesis

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    BACKGROUND: Flavivirus NS1 is a non-structural glycoprotein that is expressed on the cell surface and secreted into the extracellular space, where it acts as an antagonist of complement pathway activation. Despite its transit through the secretory pathway and intracellular localization in the lumen of the endoplasmic reticulum and Golgi vesicles, NS1 is as an essential gene for flavivirus replication. How NS1 modulates infection remains uncertain given that the viral RNA replication complex localizes to the cytosolic face of the endoplasmic reticulum. METHODS AND RESULTS: Using a trans-complementation assay, we show that viruses deleted for NS1 (∆-NS1) can be rescued by transgenic expression of NS1 from West Nile virus (WNV) or heterologous flaviviruses in the absence of adaptive mutations. In viral lifecycle experiments, we demonstrate that WNV NS1 was not required for virus attachment or input strand translation of the infectious viral RNA, but was necessary for negative and positive strand RNA synthesis and formation of the endoplasmic reticulum-associated replication complex. CONCLUSIONS: WNV RNA lacking intact NS1 genes was efficiently translated but failed to form canonical replication complexes at early times after infection, which resulted in an inability to replicate viral RNA. These results expand on prior studies with yellow fever and Kunjin viruses to show that flavivirus NS1 has an essential co-factor role in regulating replication complex formation and viral RNA synthesis

    A comparison of GC-FID and PTR-MS toluene measurements in ambient air under conditions of enhanced monoterpene loading

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    Toluene was measured using both a gas chromatographic system (GC), with a flame ionization detector (FID), and a proton transfer reaction-mass spectrometer (PTR-MS) at the AIRMAP atmospheric monitoring station Thompson Farm (THF) in rural Durham, NH during the summer of 2004. Simultaneous measurements of monoterpenes, including alpha- and beta-pinene, camphene, Delta(3)-carene, and d-limonene, by GC-FID demonstrated large enhancements in monoterpene mixing ratios relative to toluene, with median and maximum enhancement ratios of similar to 2 and similar to 30, respectively. A detailed comparison between the GC-FID and PTR-MS toluene measurements was conducted to test the specificity of PTR-MS for atmospheric toluene measurements under conditions often dominated by biogenic emissions. We derived quantitative estimates of potential interferences in the PTR-MS toluene measurements related to sampling and analysis of monoterpenes, including fragmentation of the monoterpenes and some of their primary carbonyl oxidation products via reactions with H(3)O(+), O(2)(+) and NO(+) in the PTR-MS drift tube. The PTR-MS and GC-FID toluene measurements were in good quantitative agreement and the two systems tracked one another well from the instrumental limits of detection to maximum mixing ratios of similar to 0.5 ppbv. A correlation plot of the PTR-MS versus GC-FID toluene measurements was described by the least squares regression equation y=(1.13 +/- 0.02)x-(0.008 +/- 0.003) ppbv, suggesting a small similar to 13% positive bias in the PTR-MS measurements. The bias corresponded with a similar to 0.055 ppbv difference at the highest measured toluene level. The two systems agreed quantitatively within the combined 1 sigma measurement precisions for 60% of the measurements. Discrepancies in the measured mixing ratios were not well correlated with enhancements in the monoterpenes. Better quantitative agreement between the two systems was obtained by correcting the PTR-MS measurements for contributions from monoterpene fragmentation in the PTR-MS drift tube; however, the improvement was minor (\u3c10%). Interferences in the PTRMS measurements from fragmentation of the monoterpene oxidation products pinonaldehyde, caronaldehyde and alpha-pinene oxide were also likely negligible. A relatively large and variable toluene background in the PTR-MS instrument likely drove the measurement bias; however, the precise contribution was difficult to accurately quantify and thus was not corrected for in this analysis. The results from THF suggest that toluene can be reliably quantified by PTR-MS using our operating conditions (drift tube pressure, temperature and voltage of 2.0 mbar, 45 degrees C and 600V, respectively) under the ambient compositions probed. This work extends the range of field conditions under which PTR-MS validation studies have been conducted

    Clumping Factor A Mediates Binding of Staphylococcus aureus to Human Platelets

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    The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro. When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. We have now characterized the gene disrupted in PS12 and its function in platelet binding. DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two Tn551 insertions within the clumping factor A (ClfA) locus (clfA). The first copy was upstream from the clfA start codon and appeared to have no effect on ClfA production. The second insertion was within the region encoding the serine aspartate repeat of ClfA and resulted in the production of a truncated ClfA protein that was secreted from the cell. A purified, recombinant form of the ClfA A region, encompassing amino acids 40 through 559, significantly reduced the binding of ISP479C to human platelets by 44% (P = 0.0001). Immunoprecipitation of recombinant ClfA that had been incubated with solubilized platelet membranes coprecipitated a 118-kDa platelet membrane protein. This protein does not appear to be glycoprotein IIb. These results indicate that platelet binding by S. aureus is mediated in part by the direct binding of ClfA to a novel 118-kDa platelet membrane receptor

    Response of selected plant and insect species to simulated solid rocket exhaust mixtures and to exhaust components from solid rocket fuels

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    The effects of solid rocket fuel (SRF) exhaust on selected plant and and insect species in the Merritt Island, Florida area was investigated in order to determine if the exhaust clouds generated by shuttle launches would adversely affect the native, plants of the Merritt Island Wildlife Refuge, the citrus production, or the beekeeping industry of the island. Conditions were simulated in greenhouse exposure chambers and field chambers constructed to model the ideal continuous stirred tank reactor. A plant exposure system was developed for dispensing and monitoring the two major chemicals in SRF exhaust, HCl and Al203, and for dispensing and monitoring SRF exhaust (controlled fuel burns). Plants native to Merritt Island, Florida were grown and used as test species. Dose-response relationships were determined for short term exposure of selected plant species to HCl, Al203, and mixtures of the two to SRF exhaust

    Is it still worth searching for lepton flavor violation in rare kaon decays?

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    Prospective searches for lepton flavor violation (LFV) in rare kaon decays at the existing and future intermediate-energy accelerators are considered. The proposed studies are complementary to LFV searches in muon-decay experiments and offer a unique opportunity to probe models with approximately conserved fermion-generation quantum number with sensitivity superior to that in other processes. Consequently, new searches for LFV in kaon decays are an important and independent part of the general program of searches for lepton flavor violation in the final states with charged leptons.Comment: 30 pages, 10 figures. An extended version of the talk given at the Chicago Flavor Seminar, February 27, 2004. In the new version some misprints were corrected and some new data for LFV-processes were added. The main content of the paper was not changed. The paper is published in Yad. Fiz. 68, 1272 (2005
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