<p>Shiv Nadar University is a comprehensive, multidisciplinary, research-focused, and student-centric University offering a full range of academic programs at the undergraduate, postgraduate and doctoral level. With state-of-the-art infrastructure, the University comprises of academic wings, sophisticated labs, international standard sports facilities, amphitheaters, auditorium, conference rooms and smart classrooms. The University&rsquo;s goal is to become internationally recognized for the quality of its research and creative endeavors and their applicability to improving quality of life, generating new insights and expanding the boundaries of human knowledge creativity. Committed to excellence in teaching, research and service, the University aims to serve the higher education needs of India and the world beyond.</p>

Shiv Nadar University

(SoNS) School of Natural Sciences

In the present paper Global Positioning System (GPS) as well as Very Low Frequency (VLF) measurements at multi-stations have been used to analyze ionospheric anomalies related with major earthquake (Mw = 7.4) of South West Banten (Lampung Area), Indonesia. The earthquake occurred on 02 August 2019 at 19:03:21 LT (epicenter at geog. lat = 07.22° S, long. 104.83º E, depth 10 km). Tremors due to the earthquakes were felt in Jakarta, Bandung, and several parts of Java and Sumatra and more than 160,000 people were exposed and estimated release of energy to this earthquake (EQ) was 278 GWh. In this paper statistical analysis of the GPS-TEC data clearly supports the presence of earthquake signature in the form of anomalous perturbations in total electron content (TEC). Analysis found the presence of ionospheric perturbations 0–5 days before and after the main shock of the earthquake. The anomalous perturbations in the TEC were observed from few days to few hours prior to the main shock of the earthquake. Perturbations in TEC have been found to depend on the distance as well as direction of observation point from the epicentre. In general ionospheric perturbations after the EQ at all the stations are found larger than that before the EQ. VLF signal analysis using night-time fluctuation method indicates a significant increase in VLF amplitude before couple of days of EQ. Probable mechanisms behind these perturbations associated with EQ have also been discussed. © 2021, Akadémiai Kiadó.

World University root node

Life Sciences

Acta Geodaetica et Geophysica

Ionospheric perturbations observed due to Indonesian Earthquake (Mw = 7.4) using GPS and VLF measurements at multi-stations

<p>The sphingolipid pool is key regulator of vital cellular functions in Plasmodium falciparum a causative agent for deadly malaria.&nbsp;Erythrocytes, the host for asexual stage of Plasmodium, are major reservoir for Sphingosine-1-phosphate (S1P). Erythrocyte possesses Sphingosine kinase (SphK) that catalyzed its biosynthesis from sphingosine (Sph). Since, Plasmodium lacks SphK homologous protein it can be envisaged that it co-opts sphingolipids from both intraerythrocytic as well as extracellular pools for its growth and development. Herein, by sphingosine-NBD probing, we report that infected erythrocytes imports Sph from extracellular pool, which is converted to S1P and thereby taken by P. falciparum. Next, by targeting of the SphK through specific inhibitor N,N-Dimethylsphingosine DMS, we show a reduction in erythrocyte endogenous S1P pool and SphK-phosphorylation that led to inhibition in growth and development of ring stage P. falciparum. Owing to the role of S1P in erythrocyte glycolysis we analyzed uptake of NBD-Glucose and production of lactate in DMS treated and untreated plasmodium. DMS treatment led to decreased glycolysis in Plasmodium. Interestingly the host free Plasmodium did not show any effect on glycolysis with DMS treatment indicating its host-mediated effect. Further to understand the in-vivo anti-plasmodial effects of exogenous and endogenous erythrocyte S1P level, Sphingosine-1-phosphate lyase (S1PL) inhibitor (THI), S1P and SphK-1 inhibitor (DMS), were used in Plasmodium berghei ANKA (PbA) mice model. DMS treatment led to reduction of endogenous S1P conferred significant decrease in parasite load, whereas the plasma level S1P modulated by (THI) and exogenous S1P have no effect on growth of Plasmodium. This suggested erythrocyte endogenous S1P pool is important for Plasmodium growth whereas the plasma level S1P has no effect. Altogether, this study provides insight on cellular processes regulated by S1P in&nbsp;P. falciparum&nbsp;and highlights the novel mechanistically distinct molecular target i.e. SphK-1. © 2021, The Author(s).</p>

Fulltext

Scientific Reports

Erythrocyte sphingosine kinase regulates intraerythrocytic development of Plasmodium falciparum

Severe malaria caused by Plasmodium falciparum poses a major global health problem with high morbidity and mortality. P. falciparum harbors a family of pore-forming proteins (PFPs), known as perforin like proteins (PLPs), which are structurally equivalent to prokaryotic PFPs. These PLPs are secreted from the parasites and, they contribute to disease pathogenesis by interacting with host cells. The severe malaria pathogenesis is associated with the dysfunction of various barrier cells, including endothelial cells (EC). Several factors, including PLPs secreted by parasites, contribute to the host cell dysfunction. Herein, we have tested the hypothesis that PLPs mediate dysfunction of barrier cells and might have a role in disease pathogenesis. We analyzed various dysfunctions in barrier cells following rPLP2 exposure and demonstrate that it causes an increase in intracellular Ca2+ levels. Additionally, rPLP2 exposed barrier cells displayed features of cell death, including Annexin/PI positivity, depolarized the mitochondrial membrane potential, and ROS generation. We have further performed the time-lapse video microscopy of barrier cells and found that the treatment of rPLP2 triggers their membrane blebbing. The cytoplasmic localization of HMGB1, a marker of necrosis, further confirmed the necrotic type of cell death. This study highlights the role of parasite factor PLP in endothelial dysfunction and provides a rationale for the design of adjunct therapies against severe malaria.

Toxins

Pathogenic Pore Forming Proteins of Plasmodium Triggers the Necrosis of Endothelial Cells Attributed to Malaria Severity

Clan C1A or ‘papain superfamily’ cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of a re-engineered chimera inhibitor Mco-cysteine protease inhibitor (CPI) to inhibit the activity of C1A cysteine proteases. This was accomplished by grafting the cystatin first hairpin loop conserved motif (QVVAG) onto loop 1 of the ultrastable cyclic peptide scaffold McoTI-II. The recombinantly expressed Mco-CPI protein was able to bind with micromolar affinity to papain and showed remarkable thermostability owing to the formation of multi-disulphide bonds. Using an in silico approach based on homology modelling, protein–protein docking, the calculation of the free-energy of binding, the mechanism of inhibition of Mco-CPI against representative C1A cysteine proteases (papain and cathepsin L) was validated. Furthermore, molecular dynamics simulation of the Mco-CPI–papain complex validated the interaction as stable. To conclude, in this McoTI-II analogue, the specificity had been successfully redirected towards C1A cysteine proteases while retaining the moderate affinity. The outcomes of this study pave the way for further modifications of the Mco-CPI design for realizing its full potential in therapeutics. This study also demonstrates the relevance of ultrastable peptide-based scaffolds for the development of novel inhibitors via grafting. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Pharmaceuticals

Repurposing the mcoti-ii rigid molecular scaffold in to inhibitor of ‘papain superfamily’ cysteine proteases

Full-visible color-tunable new fluorophores are essential in bioimaging research. However, it is significantly challenging to design fluorophores with the desired optical and biological properties owing to their structural complexity. We report a unified design of an interesting molecular framework, IndiFluors, based on the principle of a donor-acceptor-donor (D1-A-D2) system. The IndiFluors comprise pyrylium, pyridinium, and pyridine derivatives, which exhibit full-visible emission color (375-700 nm) by varying donor and acceptor strengths of the core scaffolds. With a minimal change of structure, the bright fluorophores (φ: 0.96) can be tuned to become nonfluorescent (φ: 0.01), which is well explained by time-dependent density functional theory (TD-DFT/PCM) by oscillator strengths in the S1 state. Within IndiFluors, pyridinium offers several advantages, including a large Stokes shift (∼154 nm) and excellent stability, compared to pentacyclic pyrylium fluorophores. Especially, the designed probe, PM-Mito-OH, demonstrated specific colocalization in mitochondria and a monitored ratiometric pH change during mitochondrial damage, autolysosomes, and the mitophagy process. Hence, IndiFluors and the derived probe show great potential for cellular pH imaging in live cells while exhibiting minimal cytotoxicity. ©

Chemistry

ACS Sensors

IndiFluors: A New Full-Visible Color-Tunable Donor-Acceptor-Donor (D1-A-D2) Fluorophore Family for Ratiometric pH Imaging during Mitophagy

An enzyme which is capable of catalyzing C–H amination reactions is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently{,} the Arnold group achieved this feat using an engineered CYP411 enzyme{,} which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calculations. The study shows that the efficient C–H amination by the engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of the axial cysteine ligand to serine relays electron density to the Fe ion in the heme{,} and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. In comparison{,} the native cysteine-ligated P450 cannot bind the tosyl azide. Additionally{,} the A78V and A82L mutations in P411 provide ‘bulk’ to the active site which increases the enantioselectivity via a steric effect. At the same time{,} the QM/MM calculations elucidate the C–H amination by the iron nitrenoid{,} revealing a mechanism analogous to Compound I in the native C–H hydroxylation by P450.

Chem. Sci.

MD simulations and QM/MM calculations reveal the key mechanistic elements which are responsible for the efficient C–H amination reaction performed by a bioengineered P450 enzyme

In present work, doping modified SrBi1.98La0.02Nb2-xTaxO9; x = 0.0–2.0 in steps of 0.5 (SBLNT) matrix is investigated for typical potential barrier formation yielding delayed dielectric relaxation and repair of weak ferroelectric character due to deterioration post microwave synthesis. Unit cell regularizes to tetragonal character on doping tantalum compared to dominant orthorhombic nature of undoped SrBi1.98La0.02Nb2O9 SBLN sample. Regular decrease in c-axis strain in the presence of fix lanthanum content is due to increased electrostatic repulsion along a-b plane on doping tantalum. Strong correlation between 4f-electrons of tantalum and intense sp3-hybridization between Ta(4f)-O(2p) electrons is discussed as a major cause for holding any unbound charge without participating in conduction. Complex impedance and modulus spectroscopy both confirm growth of highly resistive grain boundaries in sample with 50% tantalum doping. Poled and unpoled ferroelectric hysteresis loops for all samples indicate rise in ferroelectric hardness on increase in tantalum doping besides decreasing pore-size. © 2021 Elsevier B.V.

Physics

Materials Chemistry and Physics

Resistive grain boundary and double-diffused potential barrier formation for delayed dielectric relaxation in SrBi1.98La0.02Nb-TaO9 material

Single-step synthesis of core-shell diamond-graphite hybrid electrodes is demonstrated by a mere variation of CH4 concentration (CC) in the microwave growth plasma. The excellent electrochemical stability of diamond and high surface area/electrical conductivity of graphite make the hybrid electrode suitable for supercapacitor application. The supercapacitor study of the hybrid electrode is carried out using both aqueous and redox species contained electrolytes. A brilliant supercapacitor performance (specific capacitance 0.19 F cm−2) with high energy and power density and remarkable electrode retention (96% after 10,000 cycles) is obtained and discussed in the light of different electrochemical techniques such as cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy. The supercapacitor performance is explained by analyzing the microstructural evolution of diamond films from a well-faceted geometry dominated with pure diamond phase to an entirely different needle-like structure having diamond-graphite mixed phase. The CC-dependent phase transition is confirmed by X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy study. Finally, the core-shell structure of the hybrid nano-needles is confirmed by transmission electron microscopy investigations. © 2021

Electrochimica Acta

Single-step synthesis of core-shell diamond-graphite hybrid nano-needles as efficient supercapacitor electrode

1,2-Dibenzoyl-1-tert-butylhydrazine (RH-5849) and related N-alkyl-N,N′-diacylhydrazines are environmentally benign insect growth regulators. Herein, we show that an unusual nN(amide) → π*Ar interaction mediated by a hydrazide amide nitrogen atom plays a crucial role in stabilizing their biologically active trans-cis (t-c) rotameric conformations. We provide NMR and IR spectroscopic evidence for the presence of these interactions, which is also supported by X-ray crystallographic and computational studies. ©

Organic Letters

Evidence of an nN(amide) → π*ArInteraction in N-Alkyl- N, N′-diacylhydrazines

We extend Fring-Tenney approach of constructing invariants of constant mass time-dependent system to the case of a time-dependent mass particle. From a coupled set of equations described in terms of guiding parameter functions, we track down a modified Ermakov-Pinney equation involving a time-dependent mass function. As a concrete example we focus on an exponential choice of the mass function. © 2021 Institute of Physics Publishing. All rights reserved.