Use of hyperpolarized [1-C]pyruvate and [2-C]pyruvate to probe the effects of the anticancer agent dichloroacetate on mitochondrial metabolism in vivo in the normal rat

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of ¹³C metabolism in vivo at very high signal-to-noise ratio (SNR). In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine whether the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-¹³C]pyruvate and [2-¹³C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+ 181±69%, P=.025) was measured when [1-¹³C]pyruvate was injected after DCA administration, and increased glutamate (+ 74±23%, P=.004), acetoacetate (+ 504±281%, P=.009) and acetylcarnitine (+ 377±157%, P=.003) were detected when [2-¹³C]pyruvate was used.     

Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6-C2]glucose and [1,2-C2]acetate

In this work the feasibility of measuring neuronal-glial metabolism in rat brain in vivo using co-infusion of [1,6-¹³C₂]glucose and [1,2-¹³C₂]acetate was investigated. Time courses of ¹³C spectra were measured in vivo while infusing both ¹³C-labeled substrates simultaneously. Individual ¹³C isotopomers (singlets and multiplets observed in ¹³C spectra) were quantified automatically using LCModel. The distinct ¹³C spectral pattern observed in glutamate and glutamine directly reflected the fact that glucose was metabolized primarily in the neuronal compartment and acetate in the glial compartment. Time courses of concentration of singly and multiply-labeled isotopomers of glutamate and glutamine were obtained with a temporal resolution of 11 min. Although dynamic metabolic modeling of these ¹³C isotopomer data will require further work and is not reported here, we expect that these new data will allow more precise determination of metabolic rates as is currently possible when using either glucose or acetate as the sole ¹³C-labeled substrate.     

The First in Vivo Observation of C–N Coupling in Mammalian Brain

[5-¹³C,¹⁵N]Glutamine, with ¹J(¹³C–¹⁵N) of 16 Hz, was observed in vivo in the brain of spontaneously breathing rats by ¹³C MRS at 4.7 T. The brain [5-¹³C]glutamine peak consisted of the doublet from [5-¹³C,¹⁵N]glutamine and the center [5-¹³C,¹⁴N]glutamine peak, resulting in an apparent triplet with a separation of 8 Hz. The time course of formation of brain [5-¹³C,¹⁵N]glutamine was monitored in vivo with a time resolution of 20–35 min. This [5-¹³C,¹⁵N]glutamine was formed by glial uptake of released neurotransmitter [5-¹³C]glutamate and its reaction with ¹⁵NH₃ catalyzed by the glia-specific glutamine synthetase. The neurotransmitter glutamate C5 was selectively¹³C-enriched by intravenous [2,5-¹³C]glucose infusion to ¹³C-label whole-brain glutamate C5, followed by [¹²C]glucose infusion to chase ¹³C from the small and rapidly turning-over glial glutamate pool, leaving ¹³C mainly in the neurotransmitter [5-¹³C]glutamate pool, which is sequestered in vesicles until release. Hence, the observed [5-¹³C,¹⁵N]glutamine arises from a coupling between ¹³C of neuronal origin and ¹⁵N of glial origin. Measurement of the rate of brain [5-¹³C,¹⁵N]glutamine formation provides a novel noninvasive method of studying the kinetics of neurotransmitter uptake into glia in vivo, a process that is crucial for protecting the brain from glutamate excitotoxicity.     

The Impact of Ozone on the 15N Incorporation and Nitrogen Assimilation of Wheat and Maize

Abstract

Young wheat (C3) and maize (C4) plants were exposed to near-ambient concentrations of ozone in open-top chambers in order to investigate the possible effects of ozone on nitrogen metabolism. Nitrogen was supplied to the plants by adding ¹⁵N-labelled tracer substances via the soil substrate. Enzyme activities (NADH nitrate reductase, nitrite reductase, glutamine synthetase and NADH glutamate dehydrogenase) and the incorporation of ¹⁵N were determined.

The findings show that nitrogen metabolism was affected by O₃, however, there were distinct differences between the two species. In plants treated with O₃, NADH nitrate reductase activity in maize leaves was reduced, while NR activity in wheat leaves only slightly declined. Only minor changes were observed with respect to the activities of nitrite reductase, glutamine synthetase and NADH glutamate dehydrogenase.

Feeding experiments using ¹⁵NO₃ ^? showed that the incorporation of nitrate nitrogen in wheat plants exposed to ozone remains virtually unchanged, whereas in maize plants reduced incorporation rates were observed for nitrate nitrogen. The incorporation of ammonium nitrogen was distinctly increased in wheat and maize by the impact of ozone.

When investigating pigment contents, reduced levels of chlorophyll a and b and carotenoids were observed, whereas the pigment content of wheat leaves remained unchanged. These results indicate that young maize plants are more susceptible than wheat plants to short-term ozone exposure.     

2,7-Carbazole and thieno[3,4-c]pyrrole-4,6-dione based copolymers with deep highest occupied molecular orbital for photovoltaic cells

Three kinds of donor–acceptor (D–A) type photovoltaic polymers were synthesized based on 2,7-carbazole and thieno[3,4-c]pyrrole-4,6-dione (TPD). The conjugation of weakly electron (e)-donating 2,7-carbazole and strongly e-accepting TPD moieties yielded a deep highest occupied molecular orbital (HOMO) and its energy level was fine-controlled to be −5.72, −5.67 and −5.57 eV through the incorporation of thiophene (T), thieno[3,2-b]thiophene (TT) and bithiophene (BT) as a π-bridge. Polymer:[6,6]-phenyl-C₇₁ butyric acid methyl ester (PC₇₁BM) based bulk heterojunction solar cells exhibited a high open-circuit voltage (V_OC) in the range, 0.86–0.94 V, suggesting good agreement with the measured HOMO levels. Despite the high V_OC, the thiophene (or thienothiophene)-containing PCTTPD (or PCTTTPD) showed poor power conversion efficiency (PCE, 1.14 and 1.25%) because of the very low short-circuit current density (J_SC). The voltage-dependent photocurrent and photoluminescence quenching measurements suggested that hole transfer from PC₇₁BM to polymer depends strongly on the HOMO level of the polymer. The PCTTPD and PCTTTPD devices suffered from electron–hole recombination at the polymer/PC₇₁BM interfaces because of the insufficient energy offset between the HOMOs of the polymer and PC₇₁BM. The PCBTTPD:PC₇₁BM device showed the best PCE of 3.42% with a V_OC and J_SC of 0.86 V and 7.79 mA cm⁻², respectively. These results show that photovoltaic polymers should be designed carefully to have a deep HOMO level for a high V_OC and sufficient energy offset for ensuring efficient hole transfer from PC₇₁BM to the polymer.     

Novel Peak Assignments of in VivoC MRS in Human Brain at 1.5 T

¹³C MRS studies at natural abundance and after intravenous 1-¹³C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C_3β,5β, myo-inositol, glutamate C_1,2,5, glutamine C_1,2,5, N-acetyl-aspartate C_1-4,C=O, creatine CH₂, CH₃, and C_C=N, taurine C_2,3, bicarbonate HCO⁻₃ were identified. After glucose infusion ¹³C enrichment of glucose C_1α,1β, glutamate C_1-4, glutamine C_1-4, aspartate C_2,3, N-acetyl-aspartate C_2,3, lactate C₃, alanine C₃, and HCO⁻₃ were observed. The observation of ¹³C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.     

Characterization of novel cation-ordered compounds with fluorite and α-PbO2 related structures prepared by oxidation of Sn-Nb-O pyrochlore

Two cation-ordered phases were prepared by the oxidation of a pyrochlore phase as a precursor in the Sn-Nb-O system. One was a cation-ordered fluorite related phase, whose unit cell volume was eight times larger than that of the fluorite structure, similar to the κ-CeZrO₄ phase. The other was a cation-ordered α-PbO₂ phase, in which the ordered arrangement of cations was distinctly different from the well-known cation-ordered α-PbO₂ structures such as wolflamite and columbite. The chemical compositions of the phases, including valence states of cations, local structure and electronic structure near the energy band gap were studied. The compositions of the precursor and its oxidized phases were evaluated, respectively, to be Sn^II_1.62(Nb^V_1.86Sn^IV_0.14)O_6.55 and Sn^IV_0.81(Nb^V_0.93Sn^IV_0.07)O_4.085, i.e. Sn^IV_1.62(Nb^V_1.86Sn^IV_0.14)O_8.17, by TG-DTA and ICP analyses, ¹¹⁹Sn Mössbauer spectroscopy and X-ray photoemission spectroscopy. It was ascertained using IR and Raman spectroscopies that the structural framework of the cation-ordered fluorite related phase was close to that of the precursor pyrochlore phase, and the structural framework of the cation-ordered α-PbO₂ phase was distinct from that of the precursor pyrochlore. The Mössbauer parameters obtained showed a strong deviation of oxygen atoms contained in the SnO₈ polyhedron in the cation-ordered fluorite related phase from the cubic arrangement for the ideal fluorite related structure, and a lower site symmetry of Sn^IV in the cation-ordered α-PbO₂ than in rutile SnO₂. An increase in the energy band gap from ∼2.5 eV for the precursor pyrochlore to ∼3.5 eV for the oxidized phases was attributed to the vanishing of Sn 5s² lone-pair states upon oxidation of Sn^II in the precursor to Sn^IV in the oxidized phases.     

Electrolytic coloration and spectral properties of OH- and Cu-codoped NaCl crystals

OH⁻- and Cu⁺-codoped NaCl crystals are colored electrolytically by using a pointed anode and a flat cathode at various temperatures and under various voltages. Absorption and fluorescence spectral properties of colored crystals are investigated. Absorption, excitation and fluorescence spectra reveal existence of V₂, V₂^m, V₃, OH⁻, U, U_A, O²⁻–V_a⁺, O₂⁺, Cu⁺, Cu⁰, Cu⁻ and OH⁻-perturbed Cu⁺ color centers in colored crystals. Formations of color centers are explained.     

In VivoQuantitation of Cerebral Metabolite Concentrations Using Natural AbundanceC MRS at 1.5 T

A method for the quantitation of cerebral metabolites on a clinical MR scanner by natural abundance¹³C MRSin vivois described. Proton-decoupled spectra were acquired with a power deposition within FDA guidelines using a novel coil design.myo-Inositol, quantified by a separate proton MRS, and readily detectable in¹³C MRS, was used as an internal reference. Normal concentrations, measured in four control subjects, age 7 months to 12 years, were glutamate 9.9 ± 0.7, glutamine 5.6 ± 1.0, and NAA 8.8 ± 2.8 mmol/kg. In a patient diagnosed with Canavan disease, examined four times, glutamate was reduced to 46% of normal, 4.6 ± 0.5 mmol/kg. NAA was increased by 50% to 13.2 ± 1.6 mmol/kg in¹³C MRS, consistent with the 41% increase to 12.3 ± 1.1 from control 8.7 ± 1.1 mmol/kg assayed by¹H MRS. Limited concentration of glutamate may impact on glutamatergic neurons and excitatory neurotransmission in Canavan disease. Quantitation of cerebral glutamate in human brain may have clinical value in human neuropathologies in which glutamate is believed to play a central role.     

Theoretical investigation of electron paramagnetic resonance parameters and lattice distortion in α-Al2O3 crystal doped with V3+ ions

The electron paramagnetic resonance parameters D, g _∥ and g _⊥ for V³⁺ ions in α-Al₂O₃ crystals are calculated on the basis of the complete diagonalization method and the superposition model. In the calculation, the contributions of the variation of the cation–ligand bond lengths and bond angles are taken into consideration. The calculated results agree well with the experimental data. Our investigation shows that the local structure around the V³⁺ ions possesses a compressed trigonal distortion above the O^2?-triangle and an elongated trigonal distortion in the lower one.     

Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo ¹H-MRS study of an animal model for Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication.     

Comparative first-principle analysis of un-doped and V3+-doped α-ZnAl2S4 spinel

The experimental and theoretical studies of the optical properties of pure α-ZnAl₂S₄ and α-ZnAl₂S₄:V³⁺ crystals were carried out. The ab initio and crystal field calculations of the structural and optical properties of α-ZnAl₂S₄:V³⁺ were compared with the corresponding experimental data. It was shown that the lowest vanadium 3d states are located at about 1.36 eV above the valence band's top. The complete energy level scheme of the α-ZnAl₂S₄:V³⁺ system, which includes the host's electronic band structure and impurity ion's energy levels, was suggested on the basis of the performed calculations.     

The BM5Se9 phases: Mössbauer studies of the superconductors and the ferromagnets

Syntheses performed in the A₃B/MSe₂ (A = Sb, Ga, Sn) (B = Nb, V, Ta) (M = V, Nb, Ta) systems lead to the formation of B(M/A)₅Se₉ phases which could be ferromagnets or superconductors. It has been shown that the presence of V modifies the superconducting exchanges and allows ferromagnetic couplings. Mössbauer spectroscopy of both ¹²¹Sb and ¹¹⁹Sn gives local electronic structure of the SbNb₅Se₉ superconductor and the Sn_0.94Ga_0.06V_0.30Nb_4.70Se₉ ferromagnet. For the latter compound, a complete study as a function of temperature is carried out showing that the Sn environment is not modified when the ferromagnetic transition occurs. The Debye temperature is calculated and compared to those obtained for other selenide compounds.     

Characterization of nanocrystalline FeSiCr powders prepared by ball milling

FeSi₁₀Cr₁₀ powder was mechanically alloyed by high energy planetary ball milling, starting from elemental powders. The microstructural and magnetic properties of the milled powders were characterized by scanning electron microscopy, X-ray diffraction, ⁵⁷Fe Mössbauer spectrometry and a vibratory sample magnetometer.After 3 h of milling, the formation of two bcc solid solutions α-Fe₁ (Si, Cr) and α-Fe₂ (Si, Cr) is observed. Their grain sizes decrease with increase in milling time attaining, at 15 h of milling, 23 and 11 nm, respectively. Mössbauer spectra of the milled powder show the presence of two components. One is a ferromagnetic type with a broad sextuplet. Its distribution of hyperfine field is characterized by high and low hyperfine field’s peaks and a mean value of 26.5 T. The other is a single paramagnetic peak. Its low concentration increases to ∼4% at 15 h of milling. These results can be explained by different atomic environments affected by Si or/and Cr elements, as well as the increased disordered grain boundaries.Magnetic measurements of the milled FeSi₁₀Cr₁₀ alloy powder exhibit a soft ferromagnetic character with a decrease of both magnetization at saturation (Ms) and coercive force (Hc) with milling time attaining values of Ms=151 emu/g and Hc=2500 A/m at 30 h of milling time.     

In-Vacuo thermal processing of α-Al2O3 single crystals in boron ambience and its implication on TL & OSL response

Single crystals of α-Al₂O₃ (10×10 mm², 0.4 mm thick) were annealed in vacuum at about 1500 °C in the ambience of boron. The OA studies on these samples showed bands at 203, 232 and 258 nm signifying that such a treatment leads to the formation of F and F⁺ centers in significant concentrations, these bands, however, were not found in the Al₂O₃ crystals processed in the similar manner in the absence of boron. The Al₂O₃:B samples were irradiated to different absorbed doses of ⁹⁰Sr/⁹⁰Y β-source and the continuous wave OSL (CW-OSL) was recorded on the samples using 470 nm blue light stimulation. These samples have shown a linear TL and CW-OSL response in the dose range of 20 mGy to 15 Gy. The minimum detectable dose, corresponding to 3σ limit of the variation of the output of the unirradiated dosimeters, was found to be 100 μGy. Irradiated samples stored in dark at room temperature for a period of two months show negligible fading. The TL and OSL sensitivities of the samples were found to be strongly dependent on process temperature and time. The TL response is marked by the absence of low temperature peak (<100 °C), unlike the case of α-Al₂O₃:C, implying that the boron doping does not lead to formation of shallow traps. The Al₂O₃:B samples show faster photoionisation cross-section as compared to α-Al₂O₃:C. This approach of processing of single crystal Al₂O₃ in the boron ambience thus represents a potential way of introducing dosimetrically pertinent defects in Al₂O₃ single crystals.     

Optical spectroscopy of neodymium-doped calcium barium niobate ferroelectric crystals

In this work, the optical absorption, luminescence and Raman spectra of a single Ca_0.28Ba_0.72Nb₂O₆:Nd³⁺ ferroelectric crystal have been measured and compared to those obtained for the self-frequency solid-state laser converter Sr_0.61Ba_0.39Nb₂O₆:Nd³⁺ crystal. The calcium-niobate system displays a much higher transition temperature (∼150 °C) than the strontium-niobate one (∼80 °C) and so it appears as an excellent candidate for a self-frequency converter solid-state laser, more stable to pumping radiation that than based on the strontium-niobate one.     

Spin-dependent recombination of the charge-transfer state in photovoltaic polymer/fullerene blends

ABSTRACT

Q-band electron spin echo (ESE) spectroscopy was applied for studying the spin-dependent recombination of charge transfer (CT) states in the benchmark organic photovoltaics (OPV) blend of poly(3-hexylthiophene-2,5-diyl) and [6,6]-phenyl C61 butyric acid methyl ester (P3HT/PC₆₀BM). Selective microwave excitation and a special protocol for ESE data treatment allowed to suppress the ESE signal of thermalised polarons and weakly coupled CT states and to address CT states with a relatively short distance between positive and negative polarons (1.5 nm < r?<?2.5 nm). Inversion of the in-phase ESE signal with increase of the delay after laser flash was observed for the regioregular P3HT^?+/PC₆₀BM^?? CT state at a temperature of 40 K. This effect is very similar to the inversion of the time resolved (TR) EPR spectrum of the same system obtained previously. Both effects can be explained by spin-dependent recombination of the CT state, with the recombination via the triplet channel proceeding much slower than via the singlet channel. For the regiorandom P3HT^?+/PC₆₀BM^?? CT state no ESE sign inversion was observed in an analogous experiment. The result suggests the importance of CT state formation via a triplet exciton, a process which was not considered previously for the P3HT/PC₆₀BM blend.     

Electron Spin Resonance Study of γ-Irradiated Morpholinium Hexafluorophosphate

γ-Irradiation of solid ammonium compounds at low temperatures nay lead to the formation and trapping of radicals generated from the parent ammonium ions. Thus, NH₃+ was observed in NH₄PF₆ ¹ and N(CH₃)₃,⁺ was found in tetramethyl ammonium halides². Recently it has been shown that γ-irradiation of tetraalkylammonium iodides at 77 °K leads to the breaking of a C-C bond next to the nitrogen atom³ in agreement with the mass spectrometrlc studies of amines which show the fission of the α, β-C-C bond as the primary process upon electron impact⁴.     

The B 2Σ+–X 2Σ+ Transition of 12C17O+: The 2‐υ″ Progression

Abstract

Three new bands of the B ²Σ⁺–X ²Σ⁺ system of ¹²C¹⁷O⁺ have been investigated using conventional spectroscopic techniques. The spectra were observed in a graphite hollow‐cathode lamp by discharging molecular oxygen (enriched in about 45% of the ¹⁷O₂ isotope) under 1.0 Torr pressure. The rotational analysis of the 2–4, 2–5, and 2–6 bands was performed with the effective Hamiltonian of Brown (Brown et al., J. Mol. Spectrosc. 1979; 74: 294–318). Molecular constants were derived from a merge calculation, including both the current wavenumbers and the spectroscopic data published by the authors previously. The principal equilibrium constants for the ground state of ¹²C¹⁷O⁺ are ω_e=2185.9658(84), ω_e x _e = 14.7674(11), B _e=1.927001(38), α_e=1.8236(22)×10^?2, γ_e=?0.331(28)×10^?4, D _e=6.041(12)×10^?6, β_e=0.100(31)×10^?7 cm^?1, and the equilibrium constants for the excited state are σ_e=45876.499(15), ω_e=1712.201(12), ω_e x _e=27.3528(39), B _e=1.754109(35), α_e=2.8706(57)×10^?2, γ_e = ?1.15(19)×10^?4, D _e=7.491(20)×10^?6, β_e=2.13(12)×10^?7, γ_e = 2.0953(97)×10^?2, and α_γe=?9.46(59)×10^?4 cm^?1, respectively. Rydberg–Klein–Rees potential energy curves were constructed for the B ²Σ⁺ and X ²Σ⁺ states of this molecule, and Franck–Condon factors were calculated for the vibrational bands of the B–X system.     

V+注入锐钛矿TiO2第一性原理研究

用金属离子注入方法在锐钛矿TiO₂薄膜中掺杂了V⁺，采用全势线性缀加平面波方法计算了锐钛矿TiO₂及V⁺掺杂TiO₂超原胞的电子结构，通过紫外-可见吸收光谱测试方法检测了注入不同剂量的V⁺对TiO₂薄膜吸收光谱的影响.理论计算和实验结果表明，锐钛矿TiO₂薄注入V⁺后，带隙宽度变小，吸收光谱发生红移，并且TiO 关键词： +注入')" href="#">V⁺注入 2')" href="#">TiO₂ 全势线性缀加平面波方法 能带结构