Enhanced astroglial GABA uptake attenuates tonic GABA_A inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure

Pandit, Sudip,Jo, Ji Yoon,Lee, Sang Ung,Lee, Young Jae,Lee, So Yeong,Ryu, Pan Dong,Lee, Jung Un,Kim, Hyun-Woo,Jeon, Byeong Hwa,Park, Jin Bong American Physiological Society 2015 Journal of neurophysiology Vol.114 No.2

<P>γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (<I>I</I><SUB>tonic</SUB>) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABA<SUB>A</SUB> receptors (GABA<SUB>A</SUB>Rs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of <I>I</I><SUB>tonic</SUB> in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The <I>I</I><SUB>tonic</SUB> of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced <I>I</I><SUB>tonic</SUB> sensitivity to THIP argued for the decreased function of GABA<SUB>A</SUB>R δ subunits in HF, whereas similar <I>I</I><SUB>tonic</SUB> sensitivity to benzodiazepines argued against the difference of γ<SUB>2</SUB> subunit-containing GABA<SUB>A</SUB>Rs in SHAM and HF rats. HF <I>I</I><SUB>tonic</SUB> attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal <I>I</I><SUB>tonic</SUB> responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF <I>I</I><SUB>tonic</SUB> attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABA<SUB>A</SUB>Rs function, the enhanced astroglial GABA uptake-induced attenuation of <I>I</I><SUB>tonic</SUB> in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.</P>

Efficient one-pot synthesis of novel and diverse tetrahydroquinolines bearing pyranopyrazoles using organocatalyzed domino Knoevenagel/hetero Diels–Alder reactions

Pandit, Rameshwar Prasad,Lee, Yong Rok Springer-Verlag 2014 Molecular diversity Vol.18 No.1

Developmental changes in GABA_A tonic inhibition are compromised by multiple mechanisms in preadolescent dentate gyrus granule cells

Pandit, Sudip,Lee, Gyu Seung,Park, Jin Bong The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.6

The sustained tonic currents ($I_{tonic}$) generated by ${\gamma}$-aminobutyric acid A receptors ($GABA_{A}Rs$) are implicated in diverse age-dependent brain functions. While various mechanisms regulating $I_{tonic}$ in the hippocampus are known, their combined role in $I_{tonic}$ regulation is not well understood in different age groups. In this study, we demonstrated that a developmental increase in GABA transporter (GAT) expression, combined with gradual decrease in $GABA_AR{\alpha}_5$ subunit, resulted in various $I_{tonic}$ in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at infantile ($P_{6-8}$ and $P_{13-15}$) and juvenile ($P_{20-22}$ and $P_{27-29}$) stages, with stabilization observed thereafter in adolescents ($P_{34-36}$) and young adults ($P_{41-43}$). $I_{tonic}$ facilitation of a selective GAT-1 blocker (NO-711) was significantly less at $P_{6-8}$ than after $P_{13-15}$. The facilitation of $I_{tonic}$ by SNAP-5114, a GAT-3 inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In contrast, $I_{tonic}$ in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased with age during the preadolescent period, which was mimicked by $I_{tonic}$ changes in the presence of exogenous GABA. $I_{tonic}$ sensitivity to L-655,708, a $GABA_AR{\alpha}_5$ subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression of the $GABA_AR{\alpha}_5$ subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the $I_{tonic}$ regulation of altered GATs is under the final tune of $GABA_AR{\alpha}_5$ subunit activation in DGGCs at different ages.

The Sanskrit World

Pandit Usharbudh Arya M.A., Dr. 한인문화연구원 1991 한인문화논총 Vol.9ㆍ10 No.-

Novel one-pot synthesis of diverse γ,δ-unsaturated β-ketoesters by thermal cascade reactions of diazodicarbonyl compounds and enol ethers: transformation into substituted 3,5-diketoesters

Pandit, Rameshwar Prasad,Lee, Yong Rok The Royal Society of Chemistry 2014 Organic & Biomolecular Chemistry Vol.12 No.25

<P>Sequential Wolff rearrangement of α-diazo-β-ketoesters followed by trapping of the ketene intermediates with enol ethers generated a variety of γ,δ-unsaturated β-ketoesters. This method involves a novel thermal cascade reaction and allows the synthesis of γ,δ-unsaturated β-ketoesters with <I>trans</I>-stereochemistry under catalyst-free conditions. The synthesized compounds were further transformed into novel 3,5-diketoesters, which were used for the synthesis of naturally occurring 2-pyrone and 1-naphthoic acid ester.</P> <P>Graphic Abstract</P><P>Novel and efficient synthesis of diverse γ,δ-unsaturated β-ketoesters was accomplished by thermal cascade reactions of diazodicarbonyl compounds with enol ethers and the synthesized compounds were further transformed into the corresponding 3,5-diketoesters. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4ob00664j'> </P>

In situ preparation of a novel organo-inorganic 6,13-pentacenequinone-TiO2 coupled semiconductor nanosystem: a new visible light active photocatalyst for hydrogen generation

Pandit, V.,Arbuj, S.,Hawaldar, R.,Kshirsagar, P.,Mulik, U.,Gosavi, S.,Park, C. J.,Kale, B. Royal Society of Chemistry 2015 Journal of Materials Chemistry A Vol.3 No.8

<P>Previous studies related to the synthesis of stable UV-visible light active photocatalysts for hydrogen generation have been limited to inorganic semiconductors and their nano-and hetero-structures. We demonstrate here the use of an organo-inorganic 6,13-pentacenequinone (PQ)-TiO2 coupled semiconductor nanosystem as an efficient photocatalyst active in visible light for the production of hydrogen. Anatase TiO2 nanoparticles (3-5 nm) were uniformly decorated on thin sheets of monoclinic PQ by an in situ solvothermal method. These as-prepared PQ-TiO2 coupled semiconductor nanosystems had a band gap in the range 2.7-2.8 eV. The strong emission at 590 nm can be attributed to the transfer of electrons from the LUMO energy level of TiO2 to combine with the holes present in the HOMO level of PQ. This electron-hole recombination makes availability of electrons and holes in LUMO of PQ and HOMO of TiO2, respectively. This hybrid semiconductor coupled nanosystem resulted in a rate of hydrogen evolution of 36 456 mu mol h(-1) g(-1) from H2S under UV-visible light; this is four times higher than the rate obtained with TiO2 in earlier reports of UV-visible light active photocatalysts. These results open up a new path to explore inorganic systems coupled with PQ as new photoactive hybrid catalysts in a number of chemical and physicochemical processes.</P>

Enhancement of fluoride activity against Streptococcus mutans biofilms by a substance separated from Polygonum cuspidatum.

Pandit, Santosh,Kim, Hye-Jin,Park, Sung-Hee,Jeon, Jae-Gyu Harwood Academic Publishers 2012 BIOFOULING -CHUR- Vol.28 No.3

<P>Polygonum cuspidatum is a plant with spreading rhizomes and numerous reddish-brown stems that has been used in Korean folk medicine to improve oral hygiene. Nevertheless, there are no reports related to its possible effect on the virulence of dental biofilms. In this study, the ability of a fraction (F1) separated from P. cuspidatum, alone or in combination with fluoride, to disrupt virulence factors and the composition of Streptococcus mutans biofilms was examined. F1 was mainly composed of resveratrol, emodin and physcion (approximately 16.2%, 18.9% and 2.07% of the weight of F1, respectively). F1 showed inhibitory effects on acid production and F-ATPase activity of S. mutans in biofilms, and could enhance fluoride activity against acid production and acid tolerance of S. mutans in biofilms. When S. mutans biofilms were briefly treated with F1 (10 min, a total of five times), the biomass accumulation, water-insoluble polysaccharides and intracellular iodophilic polysaccharides were reduced. Furthermore, the fluoride activity against biomass accumulation was enhanced by F1. These results suggest that F1 may be useful in the control of dental biofilms and in improving the cariostatic properties of fluoride without increasing its exposure.</P>

AMPK suppresses Th2 cell responses by repressing mTORC2

Pandit Mahesh,Timilshina Maheshwor,Gu Ye,Acharya Suman,Chung Yeonseok,Seo Sang-Uk,Chang Jae-Hoon 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Allergic inflammation is a T helper 2 (Th2) cell-driven pathophysiological phenomenon, but the mechanism by which the metabolic cascade affects Th2 cell differentiation remains unclear. In this study, we investigated the roles of AMP-activated protein kinase (AMPK) and intracellular energy sensors in Th2 cell differentiation and the pathogenesis of allergic inflammation. Accordingly, T-cell-specific AMPK or Sirtuin 1 (Sirt1)-knockout mice were subjected to allergic inflammation, and their Th2 cell responses were investigated. The results demonstrated that inducing allergic inflammation in AMPK- and Sirt1-knockout mice increased Th2 cell responses and exacerbated allergic phenotypes. Furthermore, treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, ameliorated allergic inflammation in mice. Mechanistically, our findings revealed that AMPK repressed mechanistic target of rapamycin complex 2 (mTORC2), which downregulated the expression of suppressor of cytokine signaling 5 (SOCS5) in CD4+ T cells. In addition, the loss of AMPK signaling reduced SOCS5 expression and increased interleukin-4-STAT6–GATA3 axis-mediated Th2 cell differentiation. Finally, the T-cell-specific deletion of Rictor, a member of mTORC2, in Sirt1T-KO mice led to the reversal of allergic exacerbation to the level in control mice. Overall, our findings suggest that AMPK in CD4+ T cells inhibits the differentiation of Th2 cells by repressing mTORC2 and thus serves as a potential target for Th2 cell-associated diseases.

Metal–semiconductor–metal ultraviolet photodiodes based on reduced graphene oxide/GaN Schottky contacts

Pandit, Bhishma,Cho, Jaehee Elsevier 2018 THIN SOLID FILMS - Vol.660 No.-

<P><B>Abstract</B></P> <P>We report on the characteristics of reduced graphene oxide (rGO)/GaN Schottky diodes in which the reduction process is performed at various temperatures. The Schottky barrier height of the rGO/GaN Schottky diode peaks at 1.07 eV with the reduction temperature of 650 °C, caused by changes in the O-containing functional groups and surface Fermi-level pinning during thermal reduction. The interdigitated rGO/GaN metal–semiconductor–metal photodiode using GO reduced at 650 °C exhibits a responsivity of 0.128 A/W under 365-nm illumination, with a sharp cutoff near the GaN energy bandgap.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Visible-blind metal-semiconductor-metal photodiode with rGO/GaN Schottky contacts </LI> <LI> A change of the Schottky barrier height of rGO/GaN contacts with temperatures </LI> <LI> Observation of a sharp cutoff wavelength near the bandgap of GaN </LI> </UL> </P>

System reliability estimation in multicomponent exponential stress-strength models

Pandit, Parameshwar V.,Kantu, Kala J. The Korean Reliability Society 2013 International Journal of Reliability and Applicati Vol.14 No.2

A stress-strength model is formulated for a multi-component system consisting of k identical components. The k components of the system with random strengths ($X_1$, $X_2$, ${\ldots}$, $X_k$) are subjected to one of the r random stresses ($X_{k+1}$, $X_{k+2}$, ${\ldots}$, $X_{k+r}$). The estimation of system reliability based on maximum likelihood estimates (MLEs) and Bayes estimators in k component system are obtained when the system is either parallel or series with the assumption that strengths and stresses follow exponential distribution. A simulation study is conducted to compare MLE and Bayes estimator through the mean squared errors of the estimators.