Shiv Nadar University

About: Shiv Nadar University is a education organization based out in Dadri, Uttar Pradesh, India. It is known for research contribution in the topics: Population & Graphene. The organization has 1015 authors who have published 1924 publications receiving 18420 citations.

Neutral derivatives of Thioflavin T do not exhibit viscosity-dependent fluorescence

Abstract: Fluorescent molecular rotors (FMR) have wide range of applications due to high sensitivity of their emission intensity to microenvironment viscosity. Thioflavin T (ThT), which exhibits FMR properties, is widely used as fluorescent probe for in vitro detection of amyloid fibrils (AF) due to its high affinity and “light-up” feature (fluorescence quantum yield of ThT changes by ∼3 orders of magnitude upon binding to AF). At physiological pH, ThT is positively charged and, therefore, it does not cross blood-brain barrier (BBB). It has been proposed that neutral derivatives of ThT are more likely to cross BBB, which should make them suitable for in vivo applications. However, for in vivo applications as fluorescent imaging agents, the neutral ThT derivatives must retain the FMR properties of ThT. In this paper, we examined whether neutral ThT derivatives exhibit FMR properties by studying the effect of solvent viscosity on their fluorescence intensity and decay lifetime. We observed that while the cationic ThT derivatives possess FMR properties, the neutral forms behave as regular highly-emitting fluorophores. Further, quantum chemical calculations in gas phase showed significant differences in the shape of excited state potential energy surfaces for the neutral and cationic derivatives of ThT. While, for charged ThT derivatives, the E(S1*) energy is minimal for the twisted conformation with dihedral angle φ = 90° between molecular fragments, the coplanar conformation with φ = 0° (or 180°) is more favorable for the neutral derivatives. From our experimental and theoretical studies we conclude that the neutral ThT derivatives lack FMR properties as their photoexcitation does not induce twisting motion coupled with internal charge transfer and, therefore, their specificity as fluorescent imaging agents for AF detection is lower than that of parent ThT.

A preliminary explore to the forced ventilation on the toxic gas release/dispersion and the hazard mitigation within a petrochemical plant

Abstract: More than thirty-five years ago, the Bhopal disaster shook the whole world and investigators found out that many people survived just because they turned on the fans in their bedrooms. It was postulated that the forced ventilation played an important role in diluting the toxic gas and saved these people. In order to provide evidence to solve this old mystery, this research employed FLACS software to assess the hazardous degree of a toxic gas (hydrogen sulfide) leakage within a petrochemical process. Series of gas dispersion simulations were performed to actualize the hazardous characteristics and the corresponding risks of the release accident. The study shows that the hazardous level and the hazard range can be greatly influenced when parameters, such as the gas leakage circumstances (atmospheric conditions and wind speed) and the mitigation measures (direction of fans and their speed) are altered. By using explosion-proof fans in different positions and ventilation directions, combined with the natural wind in a certain direction, this research attempts to detect the best combination from various mitigation designs and to compare the influence of fan directions on hazard mitigation. It is also the first time of its kind to simulate the effect of forced ventilation on hazard mitigation within a process plant. The results show that the hazardous level of a toxic release can be effectively alleviated, when the direction of the mechanical ventilation is against the natural wind direction. With the help of the CFD simulation and the quantitative risk analysis technique, different loss prevention strategies can be tested via this method in order to establish a safer working environment.

Cyclic peptide engineered from phytocystatin inhibitory hairpin loop as an effective modulator of falcipains and potent antimalarial

Abstract: Cystatins are classical competitive inhibitors of C1 family cysteine proteases (papain family). Phytocystatin superfamily shares high sequence homology and typical tertiary structure with conserved glutamine-valine-glycine (Q-X-V-X-G) loop blocking the active site of C1 proteases. Here, we develop a cysteine-bounded cyclic peptide (CYS-cIHL) and linear peptide (CYS-IHL), using the conserved inhibitory hairpin loop amino acid sequence. Using an in silico approach based on modeling, protein-peptide docking, molecular dynamics simulations and calculation of free energy of binding, we designed and validated inhibitory peptides against falcipain-2 (FP-2) and -3 (FP-3), cysteine proteases from the malarial parasite Plasmodium falciparum. Falcipains are critical hemoglobinases of P. falciparum that are validated targets for the development of antimalarial therapies. CYS-cIHL was able to bind with micromolar affinity to FP-2 and modulate its binding with its substrate, hemoglobin in in vitro and in vivo assays. CYS-cIHL could effectively block parasite growth and displayed antimalarial activity in culture assays with no cytotoxicity towards human cells. These results indicated that cyclization can substantially increase the peptide affinity to the target. Furthermore, this can be applied as an effective strategy for engineering peptide inhibitory potency against proteases.