76 research outputs found

    Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

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    Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

    Measurement of Angular Distributions and R= sigma_L/sigma_T in Diffractive Electroproduction of rho^0 Mesons

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    Production and decay angular distributions were extracted from measurements of exclusive electroproduction of the rho^0(770) meson over a range in the virtual photon negative four-momentum squared 0.5< Q^2 <4 GeV^2 and the photon-nucleon invariant mass range 3.8< W <6.5 GeV. The experiment was performed with the HERMES spectrometer, using a longitudinally polarized positron beam and a ^3He gas target internal to the HERA e^{+-} storage ring. The event sample combines rho^0 mesons produced incoherently off individual nucleons and coherently off the nucleus as a whole. The distributions in one production angle and two angles describing the rho^0 -> pi+ pi- decay yielded measurements of eight elements of the spin-density matrix, including one that had not been measured before. The results are consistent with the dominance of helicity-conserving amplitudes and natural parity exchange. The improved precision achieved at 47 GeV, reveals evidence for an energy dependence in the ratio R of the longitudinal to transverse cross sections at constant Q^2.Comment: 15 pages, 15 embedded figures, LaTeX for SVJour(epj) document class Revision: Fig. 15 corrected, recent data added to Figs. 10,12,14,15; minor changes to tex

    Beam-Induced Nuclear Depolarisation in a Gaseous Polarised Hydrogen Target

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    Spin-polarised atomic hydrogen is used as a gaseous polarised proton target in high energy and nuclear physics experiments operating with internal beams in storage rings. When such beams are intense and bunched, this type of target can be depolarised by a resonant interaction with the transient magnetic field generated by the beam bunches. This effect has been studied with the HERA positron beam in the HERMES experiment at DESY. Resonances have been observed and a simple analytic model has been used to explain their shape and position. Operating conditions for the experiment have been found where there is no significant target depolarisation due to this effect.Comment: REVTEX, 6 pages, 5 figure

    Measurement of Longitudinal Spin Transfer to Lambda Hyperons in Deep-Inelastic Lepton Scattering

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    Spin transfer in deep-inelastic Lambda electroproduction has been studied with the HERMES detector using the 27.6 GeV polarized positron beam in the HERA storage ring. For an average fractional energy transfer = 0.45, the longitudinal spin transfer from the virtual photon to the Lambda has been extracted. The spin transfer along the Lambda momentum direction is found to be 0.11 +/- 0.17 (stat) +/- 0.03 (sys); similar values are found for other possible choices for the longitudinal spin direction of the Lambda. This result is the most precise value obtained to date from deep-inelastic scattering with charged lepton beams, and is sensitive to polarized up quark fragmentation to hyperon states. The experimental result is found to be in general agreement with various models of the Lambda spin content, and is consistent with the assumption of helicity conservation in the fragmentation process.Comment: 8 pages, 3 figures; new version has an expanded discussion and small format change

    The Flavor Asymmetry of the Light Quark Sea from Semi-inclusive Deep-inelastic Scattering

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    The flavor asymmetry of the light quark sea of the nucleon is determined in the kinematic range 0.02<x<0.3 and 1 GeV^2<Q^2<10 GeV^2, for the first time from semi-inclusive deep-inelastic scattering. The quantity (dbar(x)-ubar(x))/(u(x)-d(x)) is derived from a relationship between the yields of positive and negative pions from unpolarized hydrogen and deuterium targets. The flavor asymmetry dbar-ubar is found to be non-zero and x dependent, showing an excess of dbar over ubar quarks in the proton.Comment: 7 Pages, 2 figures, RevTeX format; slight revision in text, small change in extraction of dbar-ubar and comparison with a high q2 parameterizatio

    Measurement of the Proton Spin Structure Function g1p with a Pure Hydrogen Target

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    A measurement of the proton spin structure function g1p(x,Q^2) in deep-inelastic scattering is presented. The data were taken with the 27.6 GeV longitudinally polarised positron beam at HERA incident on a longitudinally polarised pure hydrogen gas target internal to the storage ring. The kinematic range is 0.021<x<0.85 and 0.8 GeV^2<Q^2<20 GeV^2. The integral Int_{0.021}^{0.85} g1p(x)dx evaluated at Q0^2 of 2.5 GeV^2 is 0.122+/-0.003(stat.)+/-0.010(syst.).Comment: 7 pages, 3 figures, 1 table, RevTeX late

    Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

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    In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology

    Measurement of the Spin Asymmetry in the Photoproduction of Pairs of High-pT Hadrons at HERMES

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    We present a measurement of the longitudinal spin asymmetry A_|| in photoproduction of pairs of hadrons with high transverse momentum p_T. Data were accumulated by the HERMES experiment using a 27.5 GeV polarized positron beam and a polarized hydrogen target internal to the HERA storage ring. For h+h- pairs with p_T^h_1 > 1.5 GeV/c and p_T^h_2 > 1.0 GeV/c, the measured asymmetry is A_|| = -0.28 +/- 0.12 (stat.) +/- 0.02 (syst.). This negative value is in contrast to the positive asymmetries typically measured in deep inelastic scattering from protons, and is interpreted to arise from a positive gluon polarization.Comment: 5 pages (latex), 4 figures (eps

    Measurement of the Neutron Spin Structure Function g1ng_1^n with a Polarized ^3He Target

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    Results are reported from the HERMES experiment at HERA on a measurement of the neutron spin structure function g1n(x,Q2)g_1^n(x,Q^2) in deep inelastic scattering using 27.5 GeV longitudinally polarized positrons incident on a polarized 3^3He internal gas target. The data cover the kinematic range 0.023<x<0.60.023<x<0.6 and 1(GeV/c)2<Q2<15(GeV/c)21 (GeV/c)^2 < Q^2 <15 (GeV/c)^2. The integral 0.0230.6g1n(x)dx\int_{0.023}^{0.6} g_1^n(x) dx evaluated at a fixed Q2Q^2 of 2.5(GeV/c)22.5 (GeV/c)^2 is 0.034±0.013(stat.)±0.005(syst.)-0.034\pm 0.013(stat.)\pm 0.005(syst.). Assuming Regge behavior at low xx, the first moment Γ1n=01g1n(x)dx\Gamma_1^n=\int_0^1 g_1^n(x) dx is 0.037±0.013(stat.)±0.005(syst.)±0.006(extrapol.)-0.037\pm 0.013(stat.)\pm 0.005(syst.)\pm 0.006(extrapol.).Comment: 4 pages TEX, text available at http://www.krl.caltech.edu/preprints/OAP.htm
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