Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain

This study investigates the effects of ethanol on neuronal and astroglial metabolism using ¹H‐[¹³C]‐NMR spectroscopy in conjunction with infusion of [1,6‐¹³C₂]/[1‐¹³C]glucose or [2‐¹³C]acetate, respectively. A three‐compartment metabolic model was fitted to the ¹³C turnover of Glu_C3, Glu_C4, GABA_C2, GABA_C3, Asp_C3, and Gln_C4 from [1,6‐¹³C₂]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady‐state [2‐¹³C]acetate experiment and used as constraints during the metabolic model fitting. ¹H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. Gln_C4 labeling was found to be unchanged from a 15 min infusion of [2‐¹³C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain.

     

DBC2 significantly influences cell-cycle, apoptosis, cytoskeleton and membrane-trafficking pathways

The tumor suppressor DBC2 belongs to a previously uncharacterized gene family, RHOBTB (Bric-a-brac, Tramtrack, Broad-complex). The biological roles of RHOBTB proteins, including DBC2, remain unclear. To understand the physiological functions of DBC2, a global approach was applied. Expression of DBC2 was manipulated in HeLa cells and RNA profiling of the cells was performed by microarray analyses. DBC2 was introduced into HeLa cells by a mammalian expression vector with a constitutive promoter. DBC2 knockdown was achieved by RNA interference with small interfering RNA. RNA profiles of these samples were performed by microarray analysis using Affymetrix GeneChip HG-U133A 2.0. The microarray data were analyzed by Microarray Suite 5.0 (MAS 5.0) and Robust Multichip Average (RMA). A list of genes whose expression was significantly altered (p<0.001) was generated and overlaid onto a cellular pathway map in the Ingenuity Systems' Pathway Knowledge Base (Winter'04 Release). Two networks were found to react substantially to DBC2 expression; namely, more than half of participating genes are affected. One of the networks regulates cell growth through cell-cycle control and apoptosis. The other network is related to cytoskeleton and membrane trafficking. Our findings suggest that the biological roles of DBC2 are related directly and/or indirectly to these cellular machineries.     

Genetic Structure of Tibeto-Burman Populations of Bangladesh: Evaluating the Gene Flow along the Sides of Bay-of-Bengal

Human settlement and migrations along sides of Bay-of-Bengal have played a vital role in shaping the genetic landscape of Bangladesh, Eastern India and Southeast Asia. Bangladesh and Northeast India form the vital land bridge between the South and Southeast Asia. To reconstruct the population history of this region and to see whether this diverse region geographically acted as a corridor or barrier for human interaction between South Asia and Southeast Asia, we, for the first time analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental autosomal genetic markers among aboriginal Bangladesh tribes currently speaking Tibeto-Burman language. All the three studied populations; Chakma, Marma and Tripura from Bangladesh showed strikingly high homogeneity among themselves and strong affinities to Northeast Indian Tibeto-Burman groups. However, they show substantially higher molecular diversity than Northeast Indian populations. Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both males and females in shaping the Tibeto-Burman expansion in Southern Asia. Moreover, it is noteworthy that in admixture proportion, TB populations of Bangladesh carry substantially higher mainland Indian ancestry component than Northeast Indian Tibeto-Burmans. Largely similar expansion ages of two major paternal haplogroups (O2a and O3a3c), suggested that they arose before the differentiation of any language group and approximately at the same time. Contrary to the scenario proposed for colonization of Northeast India as male founder effect that occurred within the past 4,000 years, we suggest a significantly deep colonization of this region. Overall, our extensive analysis revealed that the population history of South Asian Tibeto-Burman speakers is more complex than it was suggested before.     

A first genetic linkage map of mulberry (Morus spp.) using RAPD, ISSR, and SSR markers and pseudotestcross mapping strategy

To lay the foundation for molecular breeding efforts, the first genetic linkage map of mulberry (2n=2x=28) was constructed with 50 F1 full-sib progeny using randomly amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), and simple sequence repeat (SSR) markers and two-way pseudotestcross mapping strategy. We selected 100 RAPD, 42 ISSR, and 9 SSR primers that amplified 517 markers, of which 188 (36.36%) showed a test-cross configuration, corresponding to the heterozygous condition in one parent and null in the other. Two separate female and male maps were constructed using 94 each of female- and male-specific testcross markers, containing 12 female linkage groups and 14 male linkage groups. At a minimum logarithm of the odds (LOD) score threshold of 6.0 and at a maximum map distance of 20 cM, the female map covered a 1,196.6-cM distance, with an average distance of 15.75 cM and maximum map distance of 37.9 cM between two loci; the male-specific map covered a 1,351.7-cM distance, with an average distance of 18.78 cM and a maximum map distance between two loci is of 34.7 cM. The markers distributed randomly in all linkage groups without any clustering. All 12 linkage groups in the female-specific map consisted of 4–10 loci ranging in length from 0 to 140.4 cM, and in the male-specific map, the 13 largest linkage groups (except linkage group 12, which contained three loci) consisted of 4–12 loci, ranging in length from 53.9 to 145.9 cM and accounting for 97.22% of the total map distance. When mapping, progeny pass through their juvenile phase and assume their adult characters, mapping morphological markers and identification of quantitative trait loci for adaptive traits will be the primary target. In that sense, our map provides reference information for future molecular breeding work on Morus and its relatives.     

Improving green emission of Tb3+ ions in BaO‐B2O3‐P2O5 glasses by means of Al3+ ions

BaO‐B₂O₃‐P₂O₅ glasses doped with a fixed concentration of Tb³⁺ ions and varying concentrations of Al₂O₃ were synthesized, and the influence of the Al³⁺ ion concentration on the luminescence efficiency of the green emission of Tb³⁺ ions was investigated. The optical absorption, excitation, luminescence spectra and fluorescence decay curves of these glasses were recorded at ambient temperature. The emission spectra of terbium ions when excited at 393 nm exhibited two main groups of bands, corresponding to ⁵D₃ → ⁷F_j (blue region) and ⁵D₄ → 7F_j (green region). From these spectra, the radiative parameters, viz., spontaneous emission probability A, total emission probability A_T, radiative lifetime τ and fluorescent branching ratio β, of different transitions originating from the ⁵D₄ level of Tb³⁺ ions were evaluated based on the Judd‐Ofelt theory. A clear increase in the quantum efficiency and luminescence of the green emission of Tb³⁺ ions corresponding to ⁵D₄ → ⁷F₅ transition is observed with increases in the concentration of Al₂O₃ up to 3.0 mol%. The improvement in emission is attributed to the de‐clustering of terbium ions by Al³⁺ ions and also to the possible admixing of wave functions of opposite parities. Copyright © 2016 John Wiley & Sons, Ltd.     

Amalaki Rasayana improved memory and neuronal metabolic activity in AβPP-PS1 mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive loss of memory and cognitive function. The cerebral metabolic rate of glucose oxidation has been shown to be reduced in AD. The present study evaluated efficacy of dietary Amalaki Rasayana (AR), an Ayurvedic formulation used in Indian traditional system, in AβPP-PS1 mouse model of AD in ameliorating memory and neurometabolism, and compared with donepezil, a standard FDA approved drug for AD. The memory of mice was measured using Morris Water Maze analysis. The cerebral metabolism was followed by ¹³C labelling of brain amino acids in tissue extracts ex vivo using ¹H-[¹³C]-NMR spectroscopy together with a short time infusion of [1,6-¹³C₂]glucose to mice. The intervention with Amalaki Rasayana showed improved learning and memory in AβPP-PS1 mice. The ¹³C labelings of Glu_C4, GABA_C2 and Gln_C4 were reduced in AβPP-PS1 mice when compared with wild-type controls. Intervention of AR increased the ¹³C labelling of amino acids suggesting a significant enhancement in glutamatergic and GABAergic metabolic activity in AβPP-PS1 mice similar to that observed with donepezil treatment. These data suggest that AR has potential to improve memory and cognitive function in AD.     

Concentration dependence of luminescence efficiency of Dy3+ ions in strontium zinc phosphate glasses mixed with Pb3O4

In this work we synthesized SrO–ZnO–P₂O₅ glasses mixed with Pb₃O₄ (heavy metal oxide) and doped with different amounts of Dy₂O₃ (0.1 to 1.0 mol%). Subsequently their emission and decay characteristics were investigated as a function of Dy₂O₃ concentration. The emission spectra exhibited three principal emission bands in the visible region corresponding to ⁴F_9/2 → ⁶H_15/2 (482 nm), ⁶H_13/2 (574 nm) and ⁶H_11/2 (663 nm) transitions. With increase in the concentration of Dy₂O₃ (upto 0.8 mol%) a considerable increase in the intensity of these bands was observed and, for further increase, quenching of photoluminescence (PL) output was observed. Using emission spectra, various radiative parameters were evaluated and all these parameters were found to increase with increase in Dy₂O₃ concentration. The Y/B integral emission intensity ratio of Dy³⁺ ions evaluated from these spectra exhibited a decreasing trend with increase in the Dy₂O₃ concentration up to 0.8 mol%. Quenching of luminescence observed in the case of the glasses doped with 1.0 mol% is attributed to clustering of Dy³⁺ ions. The quantitative analysis of these results together with infra‐red (IR) spectral studies indicated that 0.8 mol% is the optimum concentration of Dy³⁺ ions needed to achieve maximum luminescence efficiency. Copyright © 2016 John Wiley & Sons, Ltd.     

An Improved Method for The Preparation Of The Phosphoramidites Of Modified 2′-Deoxynucleotides: Incorporation Of 8-Oxo-2′-Deoxy-7H-Guanosine Into Synthetic Oligomers

Abstract

3′ -O-(Diisopropylamino-2-cyanoethoxyphosphinyl)-5′ -0-(4, 4′ -dimethoxytrityl)-N²-isobutyryl-8-oxo-2′-deoxy-7H-guanosine was synthesized and used for the introduction of an 8?0×0?2′-deoxy-7H-guanosine residue into a DNA oligomer by means of automated synthesis. A modification of the preparation of the phosphoramidite markedly improves the coupling efficiency in the oligomer synthesis in this and several other cases that were tested.     

Amplification of blue emission of Tm3+ ions in Li2O-HfO2-SiO2 glass system by means of Au0 metallic particles

Li₂O-HfO₂-SiO₂-Tm₂O₃:Au₂O₃ glass samples (containing fixed content of Tm₂O₃ and different concentration of Au₂O₃) were prepared and characterized. Bearing of Au⁰ metallic particles (MPs) on improving blue emission of thulium ions (Tm³⁺) ions was explored. Optical absorption (OA) spectra exhibited multiple bands excited from ³H₆ of Tm³⁺. Additionally, a broad peak in the wavelength range 500–600 nm due to surface plasmon resonance (SPR) of Au⁰ MPs was noticed in the spectra. Photoluminescence (PL) spectra (of thulium free glasses) indicated a peak in the visible range due to sp → d electronic transition of Au⁰ MPs. Luminescence spectra of Tm³⁺ and Au₂O₃ co-doped glasses exhibited intense blue emission with substantial increase of intensity with increase of Au₂O₃ content. Bearing of Au⁰ MPs on the reinforcement of blue emission of Tm³⁺ was discussed in detail with kinetic rate equations.     

Luminescence features of Ho3+, Er3+ and Tm3+ ions in red lead added non-conventional antimony oxide glass system

In this study, a glass system based on heavy metal oxides, namely Pb₃O₄–Sb₂O₃–SiO₂, was prepared with Ho₂O₃, Er₂O₃, and Tm₂O₃ as dopants. The prepared glass were characterized using X-ray diffraction (XRD) and infrared (IR) studies. The luminescence efficiencies of the three rare earth ions viz., Ho³⁺, Er³⁺, and Tm³⁺ in the glass system were investigated, specifically focusing on green (Ho³⁺, Er³⁺), blue (Tm³⁺), and near-infrared (NIR) emissions. The optical absorption (OA) and photoluminescence (PL) spectra of RE mixed glass displayed strong bands in the visible and NIR regions, which were analyzed using the Judd–Ofelt (J–O) theory. The J–O coefficients (Ω_λ) were found to be in the order of Ω₂ > Ω₄ > Ω₆ for all the three glass. Notably, the Tm³⁺-doped glass exhibited the lowest Ω₂ value, which was attributed to a larger degree of disorder in the glass network due to lower fractions of Sb⁵⁺ and Pb⁴⁺ ions that take part in the glass network forming. This conclusion was arrived based on the IR studies. Furthermore, the quantitative analysis of PL spectra and decay curves indicated that SbHo and SbEr glass were suitable for efficient green emission, while SbTm glass is a promising choice for blue laser emission.