Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency

Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)–encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromosome 3q containing elongation factor G1 (EFG1), which encodes a mitochondrial translation factor. Sequencing of EFG1 revealed a mutation affecting a conserved residue of the guanosine triphosphate (GTP)–binding domain. These results define a new class of gene defects underlying disorders of oxidative phosphorylation

Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals.

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (αkV) and alpha-ketobutyrate (αkB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing αkV and αkB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with electron spin resonance and compared with pyruvate. The addition of <sup>13</sup> C-labeled substrates to the sample matrix altered the radical yield of the precursors. Using αkB increased the <sup>13</sup> C-labeled glucose liquid-state polarization to 16.3% ± 1.3% compared with 13.3% ± 1.5% obtained with pyruvate, and 8.9% ± 2.1% with αkV. For [1- <sup>13</sup> C]butyric acid, polarization levels of 12.1% ± 1.1% for αkV, 12.9% ± 1.7% for αkB, 1.5% ± 0.2% for OX063 and 18.7% ± 0.7% for Finland trityl, were achieved. Hyperpolarized [1- <sup>13</sup> C]butyrate metabolism in the heart revealed label incorporation into [1- <sup>13</sup> C]acetylcarnitine, [1- <sup>13</sup> C]acetoacetate, [1- <sup>13</sup> C]butyrylcarnitine, [5- <sup>13</sup> C]glutamate and [5- <sup>13</sup> C]citrate. This study demonstrates the potential of αkV and αkB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla.

To characterize and optimize javax.xml.bind.JAXBElement@7524a985 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. The T javax.xml.bind.JAXBElement@1ef4ca84 and T javax.xml.bind.JAXBElement@295b7e6f relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5-ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations. The acquisition efficiency in each cellular condition was then determined as the ratio of the signal after optimization with the reference relaxation times and after optimization with its proper relaxation times. Finally, PFC detection limits were determined. The loss of acquisition efficiency due to parameter settings optimized for the wrong temperature and cellular condition was limited to 13%. The detection limits of all PFCs were lower at 24 °C than at 37 °C and varied from 11.8 ± 3.0 mM for PFCE at 24 °C to 379.9 ± 51.8 mM for PFOB at 37 °C. Optimizing javax.xml.bind.JAXBElement@30187e57 F pulse sequences with a known phantom only leads to moderate loss in acquisition efficiency in cellular conditions that might be encountered in in vivo and in vitro experiments. Magn Reson Med 77:2263-2271, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Impact of Silicon Foliar Application on the Growth and Physiological Traits of Carthamus tinctorius L. Exposed to Salt Stress

Althought safflower is a tolerant crop against many environmental stresses, but its yield and performance reduce under stress. The aim of this experiment was to investigate the effect of silicon (Si) application on the possibility of increasing salinity resistance and related mechanisms in safflower. A greenhouse experiment was conducted to investigate the effects of Si spraying (0, 1.5 and 2.5 mM) on safflower plants grown under salt stress condition (non-saline and 10 dS m−1). Salinity reduced seedling emergence percent and rate, growth parameters and disrupted ion uptake but increased emergence time and specifc leaf weight. Spraying of Si increased plant height, fresh and dry weight, leaf area, relative water content (RWC), potassium, calcium and silicon content, while sodium absorption was decreased. As a result, the K+/Na+ and Ca2+/Na+ ratios were increased. Elevated ion contents and ratios indicate an enhanced selectivity of ion uptake following silicon application and may increase ion discrimination against Na+. Treatment with 2.5 mM Si showed the most positive effect on the measured growth traits. Decrement in leaf area ratio under salinity indicates a more severe effect of salinity on leaf area compared to biomass production. On the other hand, silicon reduced the specific leaf weight under stress and non-stress conditions, which revalues the positive effects of silicon on leaf area expansion. Improvement of RWC may a reason for the icrease in leaf area and biomass production. Data shows that spraying with Si especialy with 2.5 mM can reduce salinity stress damage to safflower and increase biomass production

Tuning Properties of Iron Oxide Nanoparticles in Aqueous Synthesis without Ligands to Improve MRI Relaxivity and SAR.

Aqueous synthesis without ligands of iron oxide nanoparticles (IONPs) with exceptional properties still remains an open issue, because of the challenge to control simultaneously numerous properties of the IONPs in these rigorous settings. To solve this, it is necessary to correlate the synthesis process with their properties, but this correlation is until now not well understood. Here, we study and correlate the structure, crystallinity, morphology, as well as magnetic, relaxometric and heating properties of IONPs obtained for different durations of the hydrothermal treatment that correspond to the different growth stages of IONPs upon initial co-precipitation in aqueous environment without ligands. We find that their properties were different for IONPs with comparable diameters. Specifically, by controlling the growth of IONPs from primary to secondary particles firstly by colloidal and then also by magnetic interactions, we control their crystallinity from monocrystalline to polycrystalline IONPs, respectively. Surface energy minimization in the aqueous environment along with low temperature treatment is used to favor nearly defect-free IONPs featuring superior properties, such as high saturation magnetization, magnetic volume, surface crystallinity, the transversal magnetic resonance imaging (MRI) relaxivity (up to r₂ = 1189 mM(-1)·s(-1) and r₂/r₁ = 195) and specific absorption rate, SAR (up to 1225.1 W·gFe(-1))

Feynman rules for the rational part of the Electroweak 1-loop amplitudes

We present the complete set of Feynman rules producing the rational terms of kind R_2 needed to perform any 1-loop calculation in the Electroweak Standard Model. Our results are given both in the 't Hooft-Veltman and in the Four Dimensional Helicity regularization schemes. We also verified, by using both the 't Hooft-Feynman gauge and the Background Field Method, a huge set of Ward identities -up to 4-points- for the complete rational part of the Electroweak amplitudes. This provides a stringent check of our results and, as a by-product, an explicit test of the gauge invariance of the Four Dimensional Helicity regularization scheme in the complete Standard Model at 1-loop. The formulae presented in this paper provide the last missing piece for completely automatizing, in the framework of the OPP method, the 1-loop calculations in the SU(3) X SU(2) X U(1) Standard Model.Comment: Many thanks to Huasheng Shao for having recomputed, independently of us, all of the ${\rm R_2}$ effective vertices. Thanks to his help and by comparing with an independent computation we performed in a general $R_\xi$ gauge, we could fix, in the present version, the following formulae: the vertex $A l \bar l$ in Eq. (3.6), the vertex $Z \phi^+ \phi^-$ in Eq. (3.8), Eqs (3.16), (3.17) and (3.18

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.

To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized <sup>13</sup> C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1- <sup>13</sup> C]pyruvic and [1- <sup>13</sup> C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Ultraviolet irradiation created nonpersistent radicals in a mixture containing <sup>13</sup> C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state <sup>13</sup> C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo <sup>13</sup> C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different <sup>13</sup> C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized <sup>13</sup> C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection