<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

The HisA enzyme catalyzes the first step of histidine biosynthesisviathe Amadori rearrangement of the substrate ProFAR. Since it possesses the most conserved and ancient TIM-barrel fold, it provides an ideal framework for bioengineering of a new function from ancestral enzymes. In the present study, first, the catalytic mechanism of HisA biosynthesis was elucidated using hybrid Quantum Mechanical/Molecular Mechanical calculations, and thereafter, key residues contributing towards the promiscuity for TrpF activity were revealed using several MD simulations of a wild type enzyme and its variant with the native (ProFAR) and promiscuous (PRA) substrates. Our study reveals that the two loops (βα)1and (βα)5on the catalytic site of the HisA enzyme have incredible adaptability for the native and promiscuous substrates. The conformational interplay between these two loops is substrate driven and precise bioengineering targeting these loops is key to the emergence of new functions. Furthermore, the study reveals a key role of the Arg 15 residue which is close to the catalytic center of the enzyme in the bifunctionality of the HisA enzyme by increasing the loop flexibility. Therefore, our study provides crucial information for future bioengineering work to use the HisA enzyme as a scaffold for new enzymatic activity. © The Royal Society of Chemistry 2021.

World University root node

Chemistry

Organic and Biomolecular Chemistry

Simulations reveal the key role of Arg15 in the promiscuous activity in the HisA enzyme

Multiple input multiple output (MIMO) approach in fiber optical communication has emerged as an effective proposition to address the ever increasing demand for information exchange. In the ergodic case, the multiple channels, associated with multiple modes or cores or both in the optical fiber, is modeled by the Jacobi ensemble of random matrices. A key quantity for assessing the performance of MIMO systems is the mutual information (MI). We focus here on the case of an arbitrary transmission covariance matrix and derive exact determinant based results for the moment generating function (MGF) of mutual information (MI), and thereby address the scenario of unequal power per excited mode. The MGF is used to obtain Gaussian- and Weibull-distribution based approximations for the probability density function (PDF), cumulative distribution function (CDF) or, equivalently, the outage probability, and also the survival function (SF) or reliability function. Moreover, a numerical Fourier inversion approach is implemented to obtain the PDF, CDF, and SF directly from the MGF. The MGF is further used to investigate the ergodic capacity, which is the first moment (mean) of the mutual information. The analytical results are found to be in excellent agreement with Monte Carlo simulations. Our study goes beyond the earlier investigations where covariance matrix proportional to identity matrix has been considered which corresponds to equal power allocation per excited mode. © 2021 Elsevier GmbH

Physics

Optik

Optical MIMO communication with unequal power allocation to channels

The graphene family, especially graphene oxide (GO), has captured increasing prospects in the biomedical field due to its excellent physicochemical properties. Understanding the health and environmental impact of GO is of great importance for guiding future applications. Although their interactions with living organisms are omnipresent, the exact molecular mechanism is yet to be established. The cellular membrane is the first barrier for a foreign molecule to interact before entering into the cell. In the present study, a model system consisting of a lipid monolayer at the air-water interface represents one of the leaflets of this membrane. Surface pressure-area isotherms and advanced synchrotron X-ray scattering techniques have been employed to comprehend the interaction by varying the electrostatics of the membrane. The results depict a strong GO interaction with positively charged phospholipids, weak interaction with zwitterionic lipids, and interestingly negligible interaction with negatively charged lipids. GO flakes induce significant changes in the out-of-plane organization of a positively charged lipid monolayer with a minor influence on in-plane assembly of lipid chains. This interaction is packing-specific, and the influence of GO is much stronger at lower surface pressure. Even though for zwitterionic phospholipids, the GO flakes may partly insert into the lipid chains, the X-ray scattering results indicate that the flakes preferentially lie horizontally underneath the positively charged lipid monolayer. This in-depth structural description may pave new perspectives for the scientific community for the development of GO-based biosensors and biomedical materials. © 2021 American Chemical Society.

ACS Applied Materials and Interfaces

Self-Assembly of Graphene Oxide Nanoflakes in a Lipid Monolayer at the Air-Water Interface

The unavailability of a suitable treatment for human Hepatitis E virus (HEV) infection necessitate the development of anti HEV drugs. The HEV papain-like cysteine proteases (HEV PCP) is a crucial target to prevent viral replication and progression. E64 is a known HEV PCP inhibitor; however, its molecular mechanism of inhibition is not yet known. Since the crystal structure of HEV PCP is not available, the primary focuses of the present study was to refine the predicted HEV PCP structural model by molecular dynamics (MD) simulation. Further, we performed a 200 ns MD simulation to understand the structural complexity of HEV PCP and the effect of E64 binding with HEV PCP. The E64 binding with active site residues Gln48, Thr51, Gln55, Cys52, Ser81, Gln 98, Cys 132, Arg158, His159, Asn 160 and Ala96 leads to reduced fluctuations in the residue at N-terminal (18–41) that include the CHC motif (26–28). However, most of the other non interacting residues, including the inter-domain linker region (46–87), showed increased fluctuations in the HEV PCP-E64 complex. The residue Asp21 and Ala96 are involved in the formation of interdomain interactions in the HEV PCP apo enzyme. While in the PCP-E64 complex, E64 binds to Ala96 and creates a steric hindrance to prevent interdomain interactions. Thus, the E64 binding reduces interdomain interactions and restrict domain movements in the HEV PCP-E64 complex. This information will be important for the chemically designing more effective derivatives of E64 developing HEV PCP specific inhibitors. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Life Sciences

Journal of Biomolecular Structure and Dynamics

Molecular docking and dynamic simulation analysis of Hepatitis E virus protease in complexing with the E64 inhibitor

<p>Two new arene ruthenium(II) complexes with chemical formula [Ru2(η6-p-cymene)2(μ-L1)(μ-Cl)Cl2] [Ru]-1 and [Ru(η6-p-cymene)(L2)Cl2] [Ru]-2 (L1 = 5-phenyl-2H-tetrazole and L2 = 2-(2H-tetrazol-5-yl)pyridine) were synthesized by the reaction of [{(η6-p-cymene)RuCl2}2] with two bidentate ligands L1 and L2. Both the complexes were structurally characterized using single-crystal X-ray diffraction and other analytical techniques. The X-ray crystal structures of both the complexes revealed the coordination of tetrazolate ligands to two Ru(II) centres in bridging mode in [Ru]-1, whereas one Ru(II) centre in [Ru]-2 in chelating fashion, with overall pseudo-octahedral geometry. The resulted complexes were screened for their cytotoxic activity against three different cancer cell lines, HCT116 (colon cancer), HepG2 (liver cancer) and MCF7 (breast cancer) under in vitro conditions. Interestingly, [Ru]-1 showed much higher cytotoxicity with respect to [Ru]-2 against all the screened cancer cell lines and even better than cisplatin. For exploring the mechanism of action of [Ru]-1, reactive oxygen species (ROS) production, alterations in mitochondrial membrane potential and gene expression profiling of apoptosis related genes (Bcl2, caspase-3 and caspase-9) were also evaluated. The cancerous cells treated with [Ru]-1 showed an increase in intracellular ROS levels, disruption of mitochondrial membrane potential, up-regulation of proapoptotic caspase-3 and caspase-9 and down-regulation of antiapoptotic Bcl2. The results concluded that [Ru]-1 induced apoptosis through oxidative stress mediated activation of intrinsic pathway by generating intracellular ROS, loss of MMP and alteration of expression of apoptosis related genes. In addition, antimetastatic activity of [Ru]-1 was observed by wound healing assay showing anti-migratory property. The dual properties, antimetastatic activity and high cytotoxicity make [Ru]-1 potent platform for the development of new anticancer agents. © 2021 John Wiley &amp; Sons, Ltd.</p>

Applied Organometallic Chemistry

In vitro evaluation of cytotoxicity and antimetastatic properties of novel arene ruthenium(II)-tetrazolato compounds on human cancer cell lines

A fully biobased benzoxazine monomer, V-fa (using vanillin and furfurylamine) was grafted onto chitosan (CS) at different weight ratios (CXVY) using “grafting to” benign Schiff base chemistry. Incorporation of V-fa onto CS increased the tensile strength and improved chemical resistance of the CS-graft-V-fa films. Reversible labile linkages, expansion of CS galleries and leaching out of phenolic species from biobased polymer films led to an improved antibacterial activity against Staphylococcus aureus, which is ∼125 times higher than the bare CS film, V-fa and oligomeric V-fa. The leached out species from films were analyzed extensively by NMR, FTIR, GPC, ABTS and HRMS analysis. Oxidative-stress seems to be responsible for antibacterial activity. Current work illustrates an attractive synthetic approach and the improved antibacterial performance of biobased CS-graft-poly(V-fa) films which may hold as a potential alternative for wound-healing and implant applications in future. © 2020 Elsevier Ltd

Carbohydrate Polymers

Antibacterial performance of fully biobased chitosan-grafted-polybenzoxazine films: Elaboration and properties of released material

Introduction: The recent outbreak of coronavirus infection by SARS-CoV-2 that started from the Wuhan Province of China in 2019 has spread to most parts of the world infecting millions of people. Although the case fatality rate of SARS-CoV-2 infection is less than the previous epidemics by other closely related coronaviruses, due to its high infectivity, the total number of SARS-CoV-2 infection-associated disease, called Covid-19, is a matter of global concern. Despite drastic preventive measures, the number of Covid-19 cases are steadily increasing, and the future course of this pandemic is highly unpredictable. The most concerning fact about Covid-19 is the absence of specific and effective preventive or therapeutic agents against the disease. Finding an immediate intervention against Covid-19 is the need of the hour. In this chapter, we have discussed the role of different branches of the cellular proteostasis network, represented by Hsp70-Hsp40 chaperone system, Ubiquitin-Proteasome System (UPS), autophagy, and endoplasmic reticulum-Unfolded Protein Response (ER-UPR) pathway in the pathogenesis of coronavirus infections and in the host antiviral defense mechanisms.Results: Based on scientific literature, we present that pharmacological manipulation of proteostasis network can alter the fate of coronavirus infections and may help to prevent the resulting pathologies like Covid-19. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Advances in Experimental Medicine and Biology

Possible Therapeutic Intervention Strategies for COVID-19 by Manipulating the Cellular Proteostasis Network

Crop productivity in legumes is determined by number and size/weight of seeds. To understand the genetic basis of seed size/weight in chickpea, we performed genome resequencing of 13 small- and 5 large-seeded genotypes using Illumina platform. Single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) differentiating small- and large-seeded genotypes were identified. A total of 17,902 SNPs and 2594 InDels located in promoter and/or coding regions that may contribute to seed size/weight were detected. Of these, 266 SNPs showed significant association with seed size/weight trait. Twenty-three genes including those involved in cell growth/division, encoding transcription factors and located within QTLs associated with seed size/weight harbored SNPs within transcription factor binding motif(s) and/or coding region. The non-synonymous SNPs were found to affect the mutational sensitivity and stability of the encoded proteins. Overall, we provided a high-quality SNP map for large-scale genotyping applications and identified candidate genes that determine seed size/weight in chickpea. © 2021 Elsevier Inc.

Genomics

Genome resequencing reveals DNA polymorphisms associated with seed size/weight determination in chickpea

Abstract: Water vapour is highly variable over tropical region and sensitive to weather condition, monsoon onset, green house effect, and pollution level in Ganga River. In the present study, variability in water vapour derived from Global Positioning System (GPS) over Varanasi (25°20′N, 82°59′E) during the period 2007–2010 has been studied. The GPS-derived water vapour (WV) has been compared with those retrieved from Moderate Resolution Imaging Spectroradiometer (MODIS) and ECMWF. The GPS-WV data concurrent to MODIS and ECMWF timing has been correlated to perform further analysis. To study the accuracy of water vapour retrieved from the MODIS and ECMWF, root mean square error (RMSE), absolute error (AE), correlation and standard deviation in it are computed with respect to GPS-derived water vapour. Analysis shows an annual correlation R2 = 86%, RMSE = 9.5 mm and AE (MODIS–GPS) = 7.0 mm in MODIS retrieval and annual correlation R2 = 86%, RMSE = 6.1 mm and AE (ECMWF–GPS) = 2.4 mm in ECMWF reanalysis retrieval. Correlation of ECMWF and MODIS datasets with the GPS datasets are found to vary significantly with seasons. The correlation is high during monsoon season and low during spring season. Water vapour is found to be an indicator for the onset of monsoon. Research Highlights: Accuracy of water vapor (WV) retrieved from the MODIS and ECMWF with respect to GPS WV.High Annual correlation of R2 = 0.86 between both MODIS–GPS and ECMWF–GPS.The correlation is high during monsoon season and low during spring season.The performance of ECMWF is found to be better than that of MODIS. © 2021, Indian Academy of Sciences.

Journal of Earth System Science

Performance of water vapour retrieval from MODIS and ECMWF and their validation with ground based GPS measurements over Varanasi

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant. © 2021, The Author(s).