Life Sciences

<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

Ionic liquids (ILs) have generated considerable attention recently because of their cytotoxicity and application as antibiotics. However, the mechanism of how they damage cell membranes is not currently well understood. In this paper, the antibacterial activities of two imidazolium-based ILs, namely 1-butyl- 3-methylimidazolium tetrafluroborate ([BMIM][BF4]) and 1-ethyl- 3-methylimidazolium tetrafluroborate ([EMIM][BF4]) have been investigated. The activity of [BMIM][BF4] on gram negative bacteria E. coli is observed to be stronger compared with the short chained [EMIM][BF4]. To explain this observation, the effects of these ILs on the self-assembled structures of model cellular membranes have been investigated. The in-plane elasticity of a monolayer formed at air-water interface by 1,2-dipalmitoyl- sn-glycero- 3-phosphocholine (DPPC) lipids was reduced in the presence of the ILs. The x-ray reflectivity studies on polymer supported lipid bilayer have shown the bilayer to shrink and correspondingly exhibit an increase in electron density. The presence of a certain mol\% of negatively charged lipid, 1,2-dipalmitoyl-rac-glycero-3-phospho-L-serine (DPPS), in DPPC mono- and bi-layers enhances the effect considerably. © 2018 Elsevier B.V.

World University root node

(SoNS) School of Natural Sciences

Physics

Chemistry and Physics of Lipids

Structural changes in cellular membranes induced by ionic liquids: From model to bacterial membranes

Urbanization destroys natural habitats, displaces native ecosystems and results in regional extinction of native species. Urbanization is also argued to cause homogenization during which native species are replaced with non-native species. Negative impact of urbanization on ecosystems and biodiversity is usually focused upon while the fact that high levels of biodiversity may flourish inside cities are frequently ignored. Cities comprise a mixture of remnants of the pre-existing urban habitats and new urban habitats. The remaining fragments of natural landscapes, and other vegetation areas constitute the green infrastructure supporting the biological diversity of cities. Several biotopes such as lawns, hedges, parklands and street trees occur in the cities. In the cities ambient temperatures are higher than those of the surrounding rural areas, exhibiting the phenomenon of urban heat island. Urban vegetation experiences longer growing seasons and exhibits earlier greening than vegetation in the surrounding rural areas. Trees comprise the natural capital assets for cities as they provide immense benefits and ecosystem services for the wellbeing of city dwellers, although there are some disservices also. Studies on urban vegetation are very few in the tropics and particularly in India. In this article we review several aspects of plant diversity in cities in order to sensitize scientists, city managers and lay public to the need for more research on socioeconomic benefits and costs of city vegetation and to augment the vegetation within cities through conservation. © 2018, Current Science Association.

Current Science

Plant diversity in cities: Call for assessment and conservation

Here, we have studied the colloidal properties of carboxyl-amine functionalized superparamagnetic iron oxide nanoparticles (SPIONs with high saturation magnetization) based ferrofluids and their heating efficacies in magnetic fluid hyperthermia (MFH) via specific absorption rate (SAR)/intrinsic loss power (ILP). Moreover, we have systematically investigated the impact of the following heat influencing factors in MFH: (i) concentrations (0.5–8 mg/ml), (ii) surface coatings (trimesic acid (TMA), pyromellitic acid (PMA), terephthalic acid (TA) and aminoterephthalic acid (ATA)), (iii) applied alternating magnetic fields (AMFs - with amplitudes (H)/frequencies (f)) - chosen near to Hergt's biological safety limit, and (iv) dispersion media (biological/non-biological) for using SPIONs in in vitro cancer hyperthermia therapy. SPIONs (particularly decorated with dual-surfactants, i.e., TA-ATA) based aqueous ferrofluids have displayed excellent time-dependent temperature rise even at lower concentrations for the applied AMFs, which resulted in enhanced SAR values ranging from 12.5–200.1 W/gFe because of their high colloidal stability and enhanced π-π conjugations from the close structural orientations of TA/ATA molecules due to high electrostatic attractions of the respective functional groups (-COOH/NH2). Moreover, high ILP values of up-to 3.9 nHm2/kg (higher than the best commercial ferrofluids) are attained on exposure to magnetic fields below the safety limit. Besides, TA-ATA coated SPIONs dispersed in biological/non-biological media have exhibited better thermal responses as compared to their aqueous counterpart and reached therapeutic temperatures at faster rates due to prominent Neel relaxation mechanisms. The highest SAR value of 276.3 W/gFe is recorded for TA-ATA coated SPIONs dispersed in triethylene glycol (TEG - with high viscosity), ascribed to the lesser inter-particle interactions from electrostatic repulsions of negative charges among carboxyl/oxygen molecules from SPIONs/TEG respectively. Moreover, TA-ATA coated SPIONs have induced almost 90\% cell death in MCF-7 cancer cells in in vitro MFH studies. Thus, the TA-ATA coated SPIONs based ferrofluids have great potential for in vivo/clinical MFH cancer therapies. © 2018 Elsevier B.V.

Journal of Molecular Liquids

Systematic investigations on heating effects of carboxyl-amine functionalized superparamagnetic iron oxide nanoparticles (SPIONs) based ferrofluids for in vitro cancer hyperthermia therapy

Palmitoylation has been recently identified as an important post-translational rheostat for controlling protein function in eukaryotes. However, the molecular machinery underlying palmitoylation remains unclear in the neglected tropical parasite, Leishmania donovani. Herein, we have identified a catalog of 20 novel palmitoyl acyltransferases (PATs) and characterized the promastigote-specific PAT (LdPAT4) containing the canonical Asp-His-His-Cys (DHHC) domain. Immunofluorescence analysis using in-house generated LdPAT4-specific antibody demonstrated distinct expression of LdPAT4 in the flagellar pocket of promastigotes. Using metabolic labeling-coupled click chemistry method, the functionality of this recombinant enzyme could be authenticated in E. coli strain expressing LdPAT4-DHHC domain. This was evident by the cellular uptake of palmitic acid analogs, which could be successfully inhibited by 2-BMP, a PAT-specific inhibitor. Using CSS-Palm based in-silico proteomic analysis, we could predict up to 23 palmitoylated sites per protein in the promastigotes, and further identify distinctive palmitoylated protein clusters involved in microtubule assembly, flagella motility and vesicular trafficking. To highlight, proteins such as Flagellar Member proteins (FLAM1, FLAM5), Intraflagellar Transport proteins (IFT88), and flagellar motor assembly proteins including the Dynein family were found to be enriched. Furthermore, analysis of global palmitoylation in promastigotes using Acyl-biotin exchange purification identified a set of S-palmitoylated proteins overlapping with the in-silico proteomics data. The attenuation of palmitoylation using 2-BMP demonstrated several phenotypic alterations in the promastigotes including distorted morphology, reduced motility (flagellar loss or slow flagellar beating), and inefficient invasion of promastigotes to host macrophages. These analyses confirm the essential role of palmitoylation in promastigotes. In summary, the findings suggest that LdPAT4 acts as a functional acyltransferase that can regulate palmitoylation of proteins involved in parasite motility and invasion, thus, can serve as a potential target for designing chemotherapeutics in Visceral Leishmaniasis. © 2018 Ayana, Yadav, Kumari, Ramu, Garg, Pati and Singh.

Fulltext

Frontiers in Cellular and Infection Microbiology

Identification and characterization of a novel palmitoyl acyltransferase as a druggable rheostat of dynamic palmitoylome in L. donovani

Tropical calcific pancreatitis (TCP) is a juvenile, non-alcoholic form of chronic pancreatitis with its exclusive presence in tropical regions associated with the low economic status. TCP initiates in the childhood itself and then proliferates silently. mutTCPdb is a manually curated and comprehensive disease specific single nucleotide variant (SNV) database. Extensive search strategies were employed to create a repository while SNV information was collected from published articles. Several existing databases such as the dbSNP, Uniprot, miRTarBase2.0, HGNC, PFAM, KEGG, PROSITE, MINT, BIOGRID 3.4 and Ensemble Genome Browser 87 were queried to collect information specific to the gene. mutTCPdb is running on the XAMPP web server with MYSQL database in the backend for data storage and management. Currently, the mutTCPdb enlists 100 variants of all 11 genes identified in TCP, out of which 45 are non-synonymous (missense, nonsense, deletions and insertions), 46 are present in non-coding regions (UTRs, promoter region and introns) and 9 are synonymous variants. The database is highly curated for disease-specific gene variants and provides complete information on function, transcript information, pathways, interactions, miRNAs and PubMed references along with remarks. It is an informative portal for clinicians and researchers for a better understanding of the disease, as it may help in identifying novel targets and diagnostic markers, hence, can be a source to improve the strategies for TCP management. © The Author(s) 2018. Published by Oxford University Press.

Database

MutTCPdb: A comprehensive database for genomic variants of a tropical country neglected disease - Tropical calcific pancreatitis

Polystyrene is a chemically inert synthetic aromatic polymer. This widely used form of plastic is recalcitrant to biodegradation. The exponential production and consumption of polystyrene in various sectors has presented a great environment risk and raised the problem of waste management. Biodegradation by bacteria has previously shown great potential against various xenobiotics but there are only a few reports concerning polyolefins. By screening wetland microbes, we found two bacterial species-Exiguobacterium sibiricum strain DR11 and Exiguobacterium undae strain DR14 which showed promising biodegradation potential against polystyrene. In this study, we report the degradation of non-irradiated solid polystyrene material after incubation with these isolates. Growth studies suggested that the Exiguobacterium strains utilize polystyrene as a carbon source. Moreover, our data suggest that polymer degradation was initiated by biofilm formation over the PS surface leading to alteration in the physical properties of the material. Surface property analysis by AFM revealed significantly enhanced roughness resulting in reduced surface hydrophobicity of polystyrene. Fourier-transfer infrared (FT-IR) spectroscopic analysis showed breakdown of polystyrene backbone by oxidation. The extent of deterioration was further determined by percent weight reduction of polystyrene after incubation with bacteria. Our data support the fact that strains of extremophile bacterium Exiguobacterium are capable of degrading polystyrene and can be further used to mitigate the environmental pollution caused by plastics. © The Royal Society of Chemistry.

RSC Advances

Biofilm formation by Exiguobacterium sp. DR11 and DR14 alter polystyrene surface properties and initiate biodegradation

Quantitative Structure Activity Relationship (QSAR) is one of the widely used ligand based drug design strategies. Although a number of QSAR studies have been reported, debates over the limitations and accuracy of QSAR models are at large. In this review the applicability of various classes of molecular descriptors in QSAR has been explained. Protocol for QSAR model development and validation is presented. Here we discuss a case study on 7-Phenyl-imidazoquinolin-4(5H)-one derivatives as potent mPGES-1 inhibitors to identify crucial physicochemical properties responsible for mPGES-1 inhibition. The case study explains the methodology for QSAR analysis, validation of the developed models and role of diverse classes of molecular descriptors in defining the inhibitory activity of considered inhibitors. Various molecular descriptors derived from 2D/3D structure and quantum mechanics were considered in the study. Initially, QSAR models for the training set compounds were developed individually for each class of molecular descriptors. Further, a combined QSAR model was developed using the best descriptor from all the classes. The models obtained were further validated using an external test set. Combined QSAR model exhibited the best correlation (r = 0.80) between the predicted and experimental biological activities of test set compounds. The results of the QSAR analysis were further backed by docking studies. From the results of the case study it is evident that rather than a single class of molecular descriptors, a combination of molecular descriptors belonging to different classes significantly improves the QSAR predictions. The techniques and protocol discussed in the present work might be of significant importance while developing QSAR models of various drug targets. © 2018 Bentham Science Publishers.

Current Topics in Medicinal Chemistry

Role of topological, electronic, geometrical, constitutional and quantum chemical based descriptors in QSAR: mPGES-1 as a case study

Ionospheric perturbations in possible association with a major earthquake (EQ) (M = 8.5) which occurred in India-Oceania region are investigated by monitoring subionospheric propagation of VLF signals transmitted from the NWC transmitter (F = 19.8 kHz), Australia to a receiving station at Varanasi (geographic lat. 25.3°N, long 82.99°E), India. The EQ occurred on 11 April 2012 at 08:38:35 h UT (magnitude ≈ 8.5, depth = 10 km, and lat. = 2.3°N, long. = 93.0°E). A significant increase of few days before the EQ has been observed by using the VLF nighttime amplitude fluctuation method (fixed frequency transmitter signal). The analysis of total electron contents (TEC) derived from the global positioning system (GPS) at three different stations namely, Hyderabad (latitude 17.38°N, longitude 78.48°E), Singapore (latitude 1.37°N, longitude 103.84°E) and Port Blair (latitude 11.62°N, longitude 92.72°E) due to this EQ has also been presented. Significant perturbation in TEC data (enhancements and depletion) is noted before and after the main shock of the EQ. The possible mechanisms behind these perturbations due to EQ have also been discussed. © 2017 COSPAR

Advances in Space Research

Seismogenic ionospheric anomalies associated with the strong Indonesian earthquake occurred on 11 April 2012 (M = 8.5)

Biophysical Journal

Structural Dynamics of Slow-Inactivation in a Voltage-Gated Sodium Channel

Sepantronium bromide (YM155) is a small molecule antitumor agent currently in phase II clinical trials. Although developed as survivin suppressor, YM155's primary mode of action has recently been found to be DNA damage. However, the mechanism of DNA damage by YM155 is still unknown. Knowing the mechanism of action of an anticancer drug is necessary to formulate a rational drug combination and select a cancer type for achieving maximum clinical efficacy. Using cell-based assays, we showed that YM155 causes extensive DNA cleavage and reactive oxygen species generation. DNA cleavage by YM155 was found to be inhibited by radical scavengers and desferal. The reducing agent DTT and the cellular reducing system xanthine/xanthine oxidase were found to reductively activate YM155 and cause DNA cleavage. Unlike quinones, DNA cleavage by YM155 occurs in the presence of catalase and under hypoxic conditions, indicating that hydrogen peroxide and oxygen are not necessary. Although YM155 is a quinone, it does not follow a typical quinone mechanism. Consistent with these observations, a mechanism has been proposed that suggests that YM155 can cause oxidative DNA cleavage upon 2-electron reductive activation. © 2018 American Chemical Society.