1,892 research outputs found
Obligatory role for phosphatidylinositol 4,5-bisphosphate in activation of native TRPC1 store-operated channels in vascular myocytes
In the present study the effect of phosphatidylinositol 4,5-bisphosphate (PIP2) was studied on a native TRPC1 store-operated channel (SOC) in freshly dispersed rabbit portal vein myocytes. Application of diC8-PIP2, a water soluble form of PIP2, to quiescent inside-out patches evoked single channel currents with a unitary conductance of 1.9 pS. DiC8-PIP2-evoked channel currents were inhibited by anti-TRPC1 antibodies and these characteristics are identical to SOCs evoked by cyclopiazonic acid (CPA) and BAPTA-AM. SOCs stimulated by CPA, BAPTA-AM and the phorbol ester phorbol 12,13-dibutyrate (PDBu) were reduced by anti-PIP2 antibodies and by depletion of tissue PIP2 levels by pre-treatment of preparations with wortmannin and LY294002. However, these reagents did not alter the ability of PIP2 to activate SOCs in inside-out patches. Co-immunoprecipitation techniques demonstrated association between TRPC1 and PIP2 at rest, which was greatly decreased by wortmannin and LY294002. Pre-treatment of cells with PDBu, which activates protein kinase C (PKC), augmented SOC activation by PIP2 whereas the PKC inhibitor chelerythrine decreased SOC stimulation by PIP2. Co-immunoprecipitation experiments provide evidence that PKC-dependent phosphorylation of TRPC1 occurs constitutively and was increased by CPA and PDBu but decreased by chelerythrine. These novel results show that PIP2 can activate TRPC1 SOCs in native vascular myocytes and plays an important role in SOC activation by CPA, BAPTA-AM and PDBu. Moreover, the permissive role of PIP2 in SOC activation requires PKC-dependent phosphorylation of TRPC1
Synchronizing Sequencing Software to a Live Drummer
Copyright 2013 Massachusetts Institute of Technology. MIT allows authors to archive published versions of their articles after an embargo period. The article is available at
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Understanding solvent spreading for Langmuir deposition of nanomaterial films: a Hansen solubility parameter approach
In order to prepare high-quality Langmuir films of two-dimensional materials it is important to select a solvent optimized for both exfoliation and spreading at the air-water interface. Whilst it is generally accepted that exfoliation and stabilisation of two-dimensional materials is well-described using the Hansen solubility parameter theory, a complementary description of solvent spreading behaviour is lacking.
To this end we develop an understanding of solvent spreading using a Hansen solubility parameter framework. Our model accurately predicts the behaviour of both water-immiscible and water-miscible solvents in Langmuir film formation experiments. We demonstrate that spreading behaviour can be modified by controlling the surface pressure of the subphase using an amphiphilic species and accordingly utilise this approach to determine the maximum spreading pressure for a selection of solvents. Ultimately, by building on this understanding we open up additional routes to optimize the preparation of Langmuir films of two-dimensional materials and other nanoparticles
Effectiveness of new agri-environment schemes in conserving arable plants in intensively farmed landscapes
Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells.
Depletion of sarcoplasmic reticulum (SR) Ca(2+) stores activates store-operated channels (SOCs) composed of canonical transient receptor potential (TRPC) 1 proteins in vascular smooth muscle cells (VSMCs), which contribute to important cellular functions. We have previously shown that PKC is obligatory for activation of TRPC1 SOCs in VSMCs, and the present study investigates if the classic phosphoinositol signaling pathway involving Gαq-mediated PLC activity is responsible for driving PKC-dependent channel gating. The G-protein inhibitor GDP-β-S, anti-Gαq antibodies, the PLC inhibitor U73122, and the PKC inhibitor GF109203X all inhibited activation of TRPC1 SOCs, and U73122 and GF109203X also reduced store-operated PKC-dependent phosphorylation of TRPC1 proteins. Three distinct SR Ca(2+) store-depleting agents, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, cyclopiazonic acid, and N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamineed, induced translocations of the fluorescent biosensor GFP-PLCδ1-PH from the cell membrane to the cytosol, which were inhibited by U73122. Knockdown of PLCβ1 with small hairpin RNA reduced both store-operated PLC activity and stimulation of TRPC1 SOCs. Immunoprecipitation studies and proximity ligation assays revealed that store depletion induced interactions between TRPC1 and Gαq, and TRPC1 and PLCβ1. We propose a novel activation mechanism for TRPC1 SOCs in VSMCs, in which store depletion induces formation of TRPC1-Gαq-PLCβ1 complexes that lead to PKC stimulation and channel gating.-Shi, J., Miralles, F., Birnbaumer, L., Large, W. A., Albert, A. P. Store depletion induces Gαq-mediated PLCβ1 activity to stimulate TRPC1 channels in vascular smooth muscle cells
The Molonglo Galactic Plane Survey: I. Overview and Images
The first epoch Molonglo Galactic Plane Survey (MGPS1) is a radio continuum
survey made using the Molonglo Observatory Synthesis Telescope (MOST) at 843
MHz with a resolution of 43" X 43" cosec |delta|. The region surveyed is 245
deg < l < 355 deg, |b| < 1.5 deg. The thirteen 9 deg X 3 deg mosaic images
presented here are the superposition of over 450 complete synthesis
observations, each taking 12 h and covering 70' X 70' cosec |delta|. The
root-mean-square sensitivity over much of the mosaiced survey is 1-2 mJy/beam
(1 sigma), and the positional accuracy is approximately 1" X 1" cosec |delta|
for sources brighter than 20 mJy. The dynamic range is no better than 250:1,
and this also constrains the sensitivity in some parts of the images. The
survey area of 330 sq deg contains well over 12,000 unresolved or barely
resolved objects, almost all of which are extra-galactic sources lying in the
Zone of Avoidance. In addition a significant fraction of this area is covered
by extended, diffuse emission associated with thermal complexes, discrete H II
regions, supernova remnants, and other structures in the Galactic interstellar
medium.Comment: Paper with 3 figures and 1 table + Table 2 + 7 jpg grayscales for Fig
4. Astrophysical Journal Supplement (in press) see also
http://www.astrop.physics.usyd.edu.au/MGP
Faraday Rotation as a diagnostic of Galactic foreground contamination of CMB maps
The contribution from the residuals of the foreground can have a significant
impact on the temperature maps of the Cosmic Microwave Background (CMB).
Mostly, the focus has been on the galactic plane, when foreground cleaning has
taken place. However, in this paper, we will investigate the possible
foreground contamination, from sources outside the galactic plane in the CMB
maps. We will analyze the correlation between the Faraday rotation map and the
CMB temperature map. The Faraday rotation map is dependent on the galactic
magnetic field, as well as the thermal electron density, and both may
contribute to the CMB temperature. We find that the standard deviation for the
mean cross correlation deviate from that of simulations at the 99.9% level.
Additionally, a comparison between the CMB temperature extrema and the extremum
points of the Faraday rotation is also performed, showing a general overlap
between the two. Also we find that the CMB Cold Spot is located at an area of
strong negative cross correlation, meaning that it may be explained by a
galactic origin. Further, we investigate nearby supernova remnants in the
galaxy, traced by the galactic radio loops. These super nova remnants are
located at high and low galactic latitude, and thus well outside the galactic
plane. We find some correlation between the Faraday Rotation and the CMB
temperature, at select radio loops. This indicate, that the galactic
foregrounds may affect the CMB, at high galactic latitudesComment: 13 pages, 22 figures, 6 table
Effect of an extreme flood event on solute transport and resilience of a mine water treatment system in a mineralised catchment
Extreme rainfall events are predicted to become more frequent with climate change and can have a major bearing on instream solute and pollutant transport in mineralised catchments. The Coledale Beck catchment in north-west England was subject to an extreme rainfall event in December 2015 that equated to a 1 in 200-year event. The catchment contains the UK's first passive metal mine water treatment system, and as such had been subject to intense monitoring of solute dynamics before and after commissioning. Due to this monitoring record, the site provides a unique opportunity to assess the effects of a major storm event on (1) catchment-scale solute transport, and (2) the resilience of the new and novel passive treatment system to extreme events. Monitoring suggests a modest decline in treatment efficiency over time that is not synchronous with the storm event and explained instead by changes in system hydraulic efficiency. There was no apparent flushing of the mine system during the event that could potentially have compromised treatment system performance. Analysis of metal transport in the catchment downstream of the mine suggests relatively subtle changes in instream chemistry with modest but statistically-significant reductions in zinc in the lower catchment irrespective of flow condition after the extreme event, but most parameters of interest show no significant change. Increased export of colloidal iron and aluminium is associated with major landslips in the mid-catchment after the storm and provide fresh sorption sites to attenuate dissolved zinc more rapidly in these locations, corroborated by laboratory experiments utilising site materials to investigate the attenuation/release of metals from stream and terrestrial sediments. The data are important as they show both the resilience of passive mine water treatment systems to extreme events and the importance of catchment-scale monitoring to ensure continued effectiveness of treatment initiatives after major perturbation
The impact of pumped water from a de-watered Magnesian limestone quarry on an adjacent wetland: Thrislington, County Durham, UK
Although quarrying is often cited as a potential threat to wetland systems, there is a lack of relevant, quantitative case studies in the literature. The impact of pumped groundwater discharged from a quarry into a wetland area was assessed relative to reference conditions in an adjacent fen wetland that receives only natural runoff. Analysis of vegetation patterns at the quarry wetland site, using Detrended Correspondence Analysis and the species indicator values of Ellenberg, revealed a clear disparity between community transitions in the quarry wetland and the reference site. Limited establishment of moisture-sensitive taxa, the preferential proliferation of robust wetland species and an overall shift towards lower species diversity in the quarry wetland were explicable primarily by the physico-chemical environment created by quarry dewatering. This encompassed high pH (up to 12.8), sediment-rich effluent creating a nutrient-poor substrate with poor moisture retention in the quarry wetland, and large fluctuations in water levels. © 2005 Elsevier Ltd. All rights reserved
Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP3 and PIP2 in rabbit coronary artery myocytes
We investigate activation mechanisms of native TRPC1/C5/C6 channels (termed TRPC1 channels) by stimulation of endothelin-1 (ET-1) receptor subtypes in freshly dispersed rabbit coronary artery myocytes using single channel recording and immunoprecipitation techniques. ET-1 evoked non-selective cation channel currents with a unitary conductance of 2.6 pS which were not inhibited by either ET(A) or ET(B) receptor antagonists, respectively BQ-123 and BQ788, when administered separately. However, in the presence of both antagonists, ET-1-evoked channel activity was abolished indicating that both ET(A) and ET(B) receptor stimulation activate this conductance. Stimulation of both ET(A) and ET(B) receptors evoked channel activity which was inhibited by the protein kinase C (PKC) inhibitor chelerythrine and by anti-TRPC1 antibodies indicating that activation of both receptor subtypes causes TRPC1 channel activation by a PKC-dependent mechanism. ET(A) receptor-mediated TRPC1 channel activity was selectively inhibited by phosphoinositol-3-kinase (PI-3-kinase) inhibitors wortmannin (50 nm) and PI-828 and by antibodies raised against phosphoinositol-3,4,5-trisphosphate (PIP(3)), the product of PI-3-kinase-mediated phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP(2)). Moreover, exogenous application of diC8-PIP(3) stimulated PKC-dependent TRPC1 channel activity. These results indicate that stimulation of ET(A) receptors evokes PKC-dependent TRPC1 channel activity through activation of PI-3-kinase and generation of PIP(3). In contrast, ET(B) receptor-mediated TRPC1 channel activity was inhibited by the PI-phospholipase C (PI-PLC) inhibitor U73122. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), an analogue of diacylglycerol (DAG), which is a product of PI-PLC, also activated PKC-dependent TRPC1 channel activity. OAG-induced TRPC1 channel activity was inhibited by anti-phosphoinositol-4,5-bisphosphate (PIP(2)) antibodies and high concentrations of wortmannin (20 μm) which depleted tissue PIP(2) levels. In addition exogenous application of diC8-PIP(2) activated PKC-dependent TRPC1 channel activity. These data indicate that stimulation of ET(B) receptors evokes PKC-dependent TRPC1 activity through PI-PLC-mediated generation of DAG and requires a permissive role of PIP(2). In conclusion, we provide the first evidence that stimulation of ET(A) and ET(B) receptors activate native PKC-dependent TRPC1 channels through two distinct phospholipids pathways involving a novel action of PIP(3), in addition to PIP(2), in rabbit coronary artery myocytes
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