413 research outputs found

    The Stargazin-Related Protein {gamma}7 Interacts with the mRNA-Binding Protein Heterogeneous Nuclear Ribonucleoprotein A2 and Regulates the Stability of Specific mRNAs, Including CaV2.2

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    The role(s) of the novel stargazin-like {gamma}-subunit proteins remain controversial. We have shown previously that the neuron-specific {gamma}7 suppresses the expression of certain calcium channels, particularly CaV2.2, and is therefore unlikely to operate as a calcium channel subunit. We now show that the effect of {gamma}7 on CaV2.2 expression is via an increase in the degradation rate of CaV2.2 mRNA and hence a reduction of CaV2.2 protein level. Furthermore, exogenous expression of {gamma}7 in PC12 cells also decreased the endogenous CaV2.2 mRNA level. Conversely, knockdown of endogenous {gamma}7 with short-hairpin RNAs produced a reciprocal enhancement of CaV2.2 mRNA stability and an increase in endogenous calcium currents in PC12 cells. Moreover, both endogenous and expressed {gamma}7 are present on intracellular membranes, rather than the plasma membrane. The cytoplasmic C terminus of {gamma}7 is essential for all its effects, and we show that {gamma}7 binds directly via its C terminus to a heterogeneous nuclear ribonucleoprotein (hnRNP A2), which also binds to a motif in CaV2.2 mRNA, and is associated with native CaV2.2 mRNA in PC12 cells. The expression of hnRNP A2 enhances CaV2.2 IBa, and this enhancement is prevented by a concentration of {gamma}7 that alone has no effect on IBa. The effect of {gamma}7 is selective for certain mRNAs because it had no effect on {alpha}2{delta}-2 mRNA stability, but it decreased the mRNA stability for the potassium-chloride cotransporter, KCC1, which contains a similar hnRNP A2 binding motif to that in CaV2.2 mRNA. Our results indicate that {gamma}7 plays a role in stabilizing CaV2.2 mRNA

    T-type Ca 2+ channels are required for enhanced sympathetic axon growth by TNFĪ± reverse signalling

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    Tumour necrosis factor receptor 1 (TNFR1)-activated TNFĪ± reverse signalling, in which membrane-integrated TNFĪ± functions as a receptor for TNFR1, enhances axon growth from developing sympathetic neurons and plays a crucial role in establishing sympathetic innervation. Here, we have investigated the link between TNFĪ± reverse signalling and axon growth in cultured sympathetic neurons. TNFR1-activated TNFĪ± reverse signalling promotes Ca2+ influx, and highly selective T-type Ca2+ channel inhibitors, but not pharmacological inhibitors of L-type, N-type and P/Q-type Ca2+ channels, prevented enhanced axon growth. T-type Ca2+ channel-specific inhibitors eliminated Ca2+ spikes promoted by TNFĪ± reverse signalling in axons and prevented enhanced axon growth when applied locally to axons, but not when applied to cell somata. Blocking action potential generation did not affect the effect of TNFĪ± reverse signalling on axon growth, suggesting that propagated action potentials are not required for enhanced axon growth. TNFĪ± reverse signalling enhanced protein kinase C (PKC) activation, and pharmacological inhibition of PKC prevented the axon growth response. These results suggest that TNFĪ± reverse signalling promotes opening of T-type Ca2+ channels along sympathetic axons, which is required for enhanced axon growth

    Development of a 0.6-MV ultracompact magnetic core pulsed transformer for high-power applications

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    The generation of high-power electromagnetic waves is one of the major applications in the field of high-intensity pulsed power. The conventional structure of a pulsed power generator contains a primary energy source and a load separated by a power-amplification system. The latter performs time compression of the slow input energy pulse and delivers a high-intensity power output to the load. Usually, either a Marx generator or a Tesla transformer is used as a power amplifier. In the present case, a system termed ā€œmodule oscillant utilisant une nouvelle architectureā€ (MOUNA) uses an innovative and very compact resonant pulsed transformer to drive a dipole antenna. This paper describes the ultracompact multiprimary winding pulsed transformer developed in common by the UniversitĆ© de Pau and Hi Pulse Company that can generate voltage pulses of up to 0.6 MV, with a rise time of less than 270 ns. The transformer design has four primary windings, with two secondary windings in parallel, and a Metglas 2605SA1 amorphous iron magnetic core with an innovative biconic geometry used to optimize the leakage inductance. The overall unit has a weight of 6 kg and a volume of only 3.4 L, and this paper presents in detail its design procedure, with each of the main characteristics being separately analyzed. In particular, simple but accurate analytical calculations of both the leakage inductance and the stray capacitance between the primary and secondary windings are presented and successfully compared with CST-based results. Phenomena such as the core losses and saturation induction are also analyzed. The resonant power-amplifier output characteristics are experimentally studied when attached to a compact capacitive load, coupled to a capacitive voltage probe developed jointly with Loughborough University. Finally, an LTspice-based model of the power amplifier is introduced and its predictions are compared with results obtained from a thorough experimental study

    Temperature dependence of Kerr constant for water at 658 nm and for pulsed intense electric fields

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    The temperature dependence of the Kerr constant for water has been determined over the range 19 Ā°C-45 Ā°C at a wavelength of 658 nm. This paper presents the experimental arrangement used for this purpose and the data obtained, for which a polynomial fit is provided. A formula is also suggested to help estimate the variation of the Kerr constant for water with both temperature and wavelength

    Spatial variability of mixing in the Southern Ocean

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    Author Posting. Ā© American Geophysical Union, 2005. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 32 (2005): L18603, doi:10.1029/2005GL023568.Strain variance from standard hydrographic profiles in the southern hemisphere oceans shows that turbulent mixing is vertically and spatially non-uniform. In the South Atlantic, Indian and South Pacific Oceans, enhanced diffusivities are found over rough topography. Consistent with internal tide generated mixing, the water column diffusivity returns to background levels 500 m to 1000 m off the sea floor. In the Southern Ocean, enhanced diffusivities throughout the entire water column below 1500 m are found in the Antarctic Circumpolar Current over complex topography. Differences in the vertical extent of enhanced diffusivity profiles in the Antarctic Circumpolar Current between the parameterizations based on tidal models and topography and of the present estimate of strain variance imply that elevated vertical diffusivity profiles in the Southern Ocean are due to the interaction between the mean geostrophic current and bottom topography.BMS was supported by the Ocean and Climate Change Institute at the Woods Hole Oceanographic Institution

    Antarctic bottom and lower circumpolar deep water circulation in the eastern Indian Ocean

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    Author Posting. Ā© American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): C02006, doi:10.1029/2005JC003011.Net northward transport below Ī³n > 28.1 kgmāˆ’3 (ā‰ˆ3200 m) into the Perth Basin of between 4.4 and 5.8 Sv is estimated from a year-long current meter mooring array between the Broken and Naturaliste Plateaus. Northward transport of between 2.0 and 2.5 Sv of Antarctic Bottom Water (Ī³n >28.2 kgmāˆ’3), that must upwell within the southern region of the Perth Basin, results in an area-averaged diapycnal velocity and diffusivity of w*=2.5āˆ’ 3.1Ɨ 10āˆ’6 msāˆ’1 and Īŗ = 13āˆ’15Ɨ10āˆ’4 m2sāˆ’1, respectively. Diffusivity estimates for the Perth Basin are several times larger than area averaged mixing estimates for the abyssal subtropical South Atlantic and Pacific Oceans. However, the dissipation of turbulent kinetic energy required to maintain the abyssal mixing in the Perth basin, Īµ=O(10āˆ’9 Wkgāˆ’1), is similar to that required in the South Atlantic Ocean. The area-averaged diffusivity in the Perth Basin does not require unreasonable energy dissipation rates as this ocean basin is only weakly stratified. The abyssal diffuvisity of the Perth Basin results from intense mixing at the basin boundary and in the basin interior over rough topography. The complex bathymetry and low abyssal stratification suggests that the Indian Ocean, for a given energy dissipation, may support a larger meridional overturning circulation than other subtropical basins.BMS was supported by funds from the Ocean and Climate Change Institute at the Woods Hole Oceanographic Institution, and The James S. Cole and Cecily C. Selby Endowed Fund and The Penzance Endowed Fund in support of Assistant Scientists. The mooring array was funded by Australiaā€™s CSIRO Marine Research
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