50 research outputs found
Modulation of Aβ42 Fibrillation in the Presence of Vitamin A Metabolite: Insights from Molecular Dynamics Simulations
No full textAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by misfolding and consequent aggregation of amyloid-β (Aβ) protein, resulting in the formation of amyloid plaques within the brain. The best possible therapy approach for AD treatment is to prevent Aβ aggregation. Joshi et al. evaluated 18 fat-soluble and water-soluble vitamins and reported vitamin A metabolite (retinoic acid) significantly inhibited Aβ42 aggregation. Thioflavin T (ThT) fluorescence analysis depicted a concentration-dependent decrease in both the primary and secondary nucleation process of Aβ42 on the inclusion of retinoic acid. Moreover, dynamic light scattering (DLS) analysis did not depict the presence of large assemblies for retinoic acid alone. Co-incubation of Aβ42 oligomer with retinoic acid notably increased the cell viability to 97 ± 6% highlighting reduction of cytotoxicity of Aβ42 oligomers by retinoic acid. Besides extensive experimental research, the molecular interactions and binding mechanism behind the inhibitory potential of retinoic acid on Aβ42 aggregation is still unknown. Thus, computational techniques to investigate the molecular mechanism in which retinoic acid blocks self-fibrillation of Aβ42 aggregation were performed. The molecular docking result highlighted favourable binding of retinoic acid with Aβ42 monomer having binding energy ̶ 6.10 kcal mol-1. The RMSD and RMSF analyses depicted reduced conformational fluctuations in Aβ42 monomer on the addition of retinoic acid. Notably, an increase in helix content was observed in the Aβ42 monomer from 44.80 ± 2.20 to 54.40 ± 0.88% which depicted reduced aggregation propensity of Aβ42 monomer in the presence of retinoic acid. Moreover, the average number of intramolecular hydrogen bonds was increased from 19.10 ± 0.96 to 21.07 ± 1.05 on the incorporation of retinoic acid, which confirms the increase in the helical conformation of Aβ42 monomer. PCA, FEL, and conformational clustering analyses depicted enhanced conformational homogeneity of Aβ42 monomer-retinoic acid complex. The binding free energy analysis (ΔGbinding= –54.89 ± 14.07 kJ mol-1) indicated favourable binding of retinoic acid with Aβ42 monomer. Additionally, binding of central hydrophobic core (CHC) residues Leu17 (–5.95 kJ mol-1), Phe20 (–6.19 kJ mol-1), and Ala21 (–3.53 kJ mol-1) of Aβ42 monomer to retinoic acid highlighted the lower aggregation tendency of Aβ42 monomer. The molecular insights into binding interactions of retinoic acid to Aβ42 peptide will be beneficial for designing new potent inhibitors as a therapeutic approach against AD
HARKISHAN SINGH SURJEET AS A COMMUNIST
No full textHarkishan Singh Surjeet was among the few Communist leaders to have left an indelible imprint on the national polity, the others being P.C. Joshi, Ajoy Ghosh, S.A. Dange, Bhupesh Gupta, E.M.S. Namboodiripad. Others like Jyoti Basu, A.K. Gopalan, P. Sundarayya, P. Ramamurti, C. Rajeswara Rao, Bhowani Sen, C. Achutha Menon had doubtless contributed to the Communist Party’s development in different regions of the country but they didn’t contribute towards shaping national political events. And it can be stated without any exaggeration that apart from EMS, Surjeet was the only CPM leader to have a genuine national perspective and even here Surjeet was able to comprehend, far more than EMS or any other CPM leader, the complexities of the Hindi heartland. Surjeet’s contribution to the national polity was not commensurate with his party’s influence or sweep – the individual Surjeet’s stature and authority in national affairs far exceeded the CPM’s standing on the national plane
Post-modern India and Identity Politics in Aravind Adiga’s The White Tiger: An Exploration
Get PDFThe White Tiger which has been charged of being a booker’s book and not a bright book of life shows us the rotten society of post-modern India. A society where corruption has become rampant; where politics is the roost of crooked people; where elections are sold and bought routinely for political mileage. The whole novel seems to be a game of identity where the haves are trying to maintain their self-hood and have-nots are seekers of self-hood. Adiga has tried to show how in the ruse of India-shining, India herself is hiding her original identity of India-struggling; in the ruse of the White Tiger the novelist depicts what is hidden and sidelined in the booklets of our diplomats
India Told and Exposed: A Reading of the Indian Booker Heavyweights
Get PDFIt’s always very dicey to speak anything about a multifarious country like India for sure. And from literature one must never expect a Kodak-camera realism. In little over a decade, three Indian writers bagged the prestigious Booker-prize, a tradition that the fiction giant Rushdie started in 1981. Here I intentionally drop V.S. Naipaul as he is of Indian ancestry and not of Indian origin. The works of all the four Indian Booker- prize winners depict a picture of the country that annoys many of the intellectuals and laymen as well. These novels have been received with considerable antagonism in India. In place of telling India, these novelists have been charged of selling India, keeping the western audience in their minds. They have been charged of tarnishing the image of the country
ε-Controlled-Replicate: An ImprovedControlled-Replicate Algorithm for Multi-way Spatial Join Processing on Map-Reduce
No full textArticle (in 'The National Herald') : ''Communist Cannot Deliver The Goods Alone: Bhupesh Gupta.''
No full textDespatch (by Special Correspondent) : '' Sri Bhupesh Gupta On I.L.C. Enquiry Report In Rajya Sabha On Friday, 11th September, 1959.''
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