Possible modulation of dopaminergic neurotransmission function by acetyl-L-carnitine

Acetyl‐L‐Carnitine (ALC) has a putative neuroprotective effect being used in a variety of conditions. Nevertheless, the underlying molecular mechanisms, particularly regarding the induction of changes in neurotransmitter systems, are still not fully understood. We aim to contribute for the elucidation of the mechanisms by which ALC alters neurotransmitter release, using a cell line and an animal model of exposure to methamphetamine (METH). PC12 cells were incubated with several doses of ALC (0.01 to 1.0 mM) alone or in combination with METH 1.0 or 100 µM for 24h or 72h. When combined, ALC preceded METH administration in 30 minutes. Dopamine (DA) content was determined by high performance liquid chromatography. C57BL/6J mice were used for in vivo assays to assess DA striatal binding. Mice were divided into 4 groups, according to different treatments: group 1 (control), group 2 (ALC, 100 mg/kg), group 3 (METH, 10 mg/kg) and group 4 (ALC+METH). Images were acquired in a SPECT/CT scanner (NanoSPECT/CT, Mediso, Hungary) 70 minutes after 123I‐IBZM injection. Regions of interest were drawn in the striata and in the cerebellum to determine the striatal binding ratio. Increased intracellular levels of DA were observed in PC12 cells at 24h and 72h after the administration of ALC. Cells treated with METH 100 µM displayed decreased intracellular levels of DA. ALC prevented the METH‐induced decrease in DA concentration (p<0.0001). On the other hand, a single dose of 10 mg/kg of METH induced a decrease in striatal D2R binding ratios comparing to control group (between 20% and 30%). Interestingly, over time, ALC was able to reverse the decrease on the radiotracer binding induced by METH. The present study indicates a possible effect of ALC over METH‐induced DA release.info:eu-repo/semantics/publishedVersio

Dispatchable High-Power Wind Turbine Based on a Multilevel Converter with Modular Structure and Hybrid Energy Storage Integration

This paper presents a new multilevel converter solution with modular structure and hybrid energy-storage integration suitable to drive modern/future high-power medium-voltage wind turbines. The hybrid energy-storage integration means that part of the converter submodules are built with batteries and part of them with conventional capacitors. Since traditional wind turbines are non-dispatchable generators, the integration of an energy storage system could be beneficial in multiple ways as the wind power plant could provide stability support to the grid, improvement of the unit commitment and economic dispatch, and the power plant owner could increase his revenues in the electricity market. The capacitors of the proposed converter are responsible to transfer the power produced by the wind turbine to the grid, and the batteries are only charged/discharged with the mismatch between the power produced by the turbine and the power to be injected into the grid, considering a dispatchable operation where the power injected into the grid is different from the power generated by the turbine. The medium-voltage structure could be an interesting option to overcome problems related to high currents in modern/future high-power wind turbines resulting in more efficient, more compact and lighter solutions. Modular multilevel converters are suitable to handle medium-voltage levels and they allow for a straightforward integration of energy storage systems in a decentralized manner

Fast DNA translocation through a solid-state nanopore

We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the driving. We show that this is the case in our experiments and derive a power-law scaling with an exponent of 1.18, in excellent agreement with our data.Comment: 5 pages, 2 figures. Submitted to PR

Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute

Hemoglobin (Hb)-based oxygen carriers (HBOC) are modified extracellular proteins, designed to replace or augment the oxygen-carrying capacity of erythrocytes. However, clinical results have generally been disappointing due to adverse side effects, in part linked to the intrinsic oxidative toxicity of Hb. Previously a redox-active tyrosine residue was engineered into the Hb β subunit (βF41Y) to facilitate electron transfer between endogenous antioxidants such as ascorbate and the oxidative ferryl heme species, converting the highly oxidizing ferryl species into the less reactive ferric (met) form. We inserted different single tyrosine mutations into the α and β subunits of Hb to determine if this effect of βF41Y was unique. Every mutation that was inserted within electron transfer range of the protein surface and the heme increased the rate of ferryl reduction. However, surprisingly, three of the mutations (βT84Y, αL91Y and βF85Y) also increased the rate of ascorbate reduction of ferric(met) Hb to ferrous(oxy) Hb. The rate enhancement was most evident at ascorbate concentrations equivalent to that found in plasma (< 100 μM), suggesting that it might be of benefit in decreasing oxidative stress in vivo. The most promising mutant (βT84Y) was stable with no increase in autoxidation or heme loss. A decrease in membrane damage following Hb addition to HEK cells correlated with the ability of βT84Y to maintain the protein in its oxygenated form. When PEGylated and injected into mice, βT84Y was shown to have an increased vascular half time compared to wild type PEGylated Hb. βT84Y represents a new class of mutations with the ability to enhance reduction of both ferryl and ferric Hb, and thus has potential to decrease adverse side effects as one component of a final HBOC product

Al(OH)(3) facilitated synthesis of water-soluble, magnetic, radiolabelled and fluorescent hydroxyapatite nanoparticles

Magnetic and fluorescent hydroxyapatite nanoparticles were synthesised using Al(OH)3-stabilised MnFe2O4 or Fe3O4 nanoparticles as precursors. They were readily and efficiently radiolabelled with 18F. Bisphosphonate polyethylene glycol polymers were utilised to endow the nanoparticles with excellent colloidal stability in water and to incorporate cyclam for high affinity labelling with 64Cu

Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma)

The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma and Bs0 -> phi gamma has been measured using 0.37 fb-1 of pp collisions at a centre of mass energy of sqrt(s) = 7 TeV, collected by the LHCb experiment. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) = 1.12 +/- 0.08 ^{+0.06}_{-0.04} ^{+0.09}_{-0.08}, where the first uncertainty is statistical, the second systematic and the third is associated to the ratio of fragmentation fractions fs/fd. Using the world average for BR(B0 -> K*0 gamma) = (4.33 +/- 0.15) x 10^{-5}, the branching fraction BR(Bs0 -> phi gamma) is measured to be (3.9 +/- 0.5) x 10^{-5}, which is the most precise measurement to date.Comment: 15 pages, 1 figure, 2 table

Measurement of the CKM angle γ from a combination of B±→Dh± analyses

A combination of three LHCb measurements of the CKM angle γ is presented. The decays B±→D K± and B±→Dπ± are used, where D denotes an admixture of D0 and D0 mesons, decaying into K+K−, π+π−, K±π∓, K±π∓π±π∓, K0Sπ+π−, or K0S K+K− final states. All measurements use a dataset corresponding to 1.0 fb−1 of integrated luminosity. Combining results from B±→D K± decays alone a best-fit value of γ =72.0◦ is found, and confidence intervals are set γ ∈ [56.4,86.7]◦ at 68% CL, γ ∈ [42.6,99.6]◦ at 95% CL. The best-fit value of γ found from a combination of results from B±→Dπ± decays alone, is γ =18.9◦, and the confidence intervals γ ∈ [7.4,99.2]◦ ∪ [167.9,176.4]◦ at 68% CL are set, without constraint at 95% CL. The combination of results from B± → D K± and B± → Dπ± decays gives a best-fit value of γ =72.6◦ and the confidence intervals γ ∈ [55.4,82.3]◦ at 68% CL, γ ∈ [40.2,92.7]◦ at 95% CL are set. All values are expressed modulo 180◦, and are obtained taking into account the effect of D0–D0 mixing