<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 GroEL/ES chaperonin cavity surface charge properties, especially the negative charges, play an important role in its capacity to assist intracavity protein folding. Remarkably, the larger fraction of GroEL/ES negative charges are not conserved among different bacterial species, resulting in a large variation in negative-charge density in the GroEL/ES cavity across prokaryotes. Intriguingly, eukaryotic GroEL/ES homologs have the lowest negative-charge density in the chaperonin cavity. This prompted us to investigate if GroEL's chaperoning mechanism changed during evolution. Using a model in vivo GroEL/ES substrate, we show that the ability of GroEL/ES to buffer entropic traps in the folding pathway of its substrate was partially dependent upon the negativecharge density inside its cavity. While this activity of GroEL/ES was found to be essential for Escherichia coli, it has been perfected in some organisms and diminished in others. However, irrespective of their charges, all the tested homologs retained their ability to regulate polypeptide chain collapse and remove enthalpic traps from folding pathways. The ability of these GroEL/ES homologs to buffer mutational variations in a model substrate correlated with their negative-charge density. Thus, Hsp60/10 chaperonins in different organisms may have changed to accommodate a different spectrum of mutations on their substrates. © 2022 National Academy of Sciences. All rights reserved.

World University root node

Life Sciences

Proceedings of the National Academy of Sciences of the United States of America

Conserved and divergent chaperoning effects of Hsp60/10 chaperonins on protein folding landscapes

Drought stress limits plant growth, resulting in a significant yield loss in chickpea. The diversification in genome sequence and selective sweep of allele(s) in different genotypes of a crop plant may play an important role in the determination of agronomic traits, including drought stress response. We investigated, via whole genome resequencing, the DNA polymorphisms between two sets of chickpea genotypes with contrasting drought stress responses (3 drought-sensitive vs. 6 drought-tolerant). In total, 36,406 single nucleotide polymorphisms (SNPs) and 3407 insertions or deletions (InDels) differentiating drought-sensitive and drought-tolerant chickpea genotypes were identified. Interestingly, most (91%) of these DNA polymorphisms were located in chromosomes 1 and 4. The genes harboring DNA polymorphisms in their promoter and/or coding regions and exhibiting differential expression under control and/or drought stress conditions between/within the drought-sensitive and tolerant genotypes were found implicated in the stress response. Furthermore, we identified DNA polymorphisms within the cis-regulatory motifs in the promoter region of abiotic stress-related and QTL-associated genes, which might contribute to the differential expression of the candidate drought-responsive genes. In addition, we revealed the effect of nonsynonymous SNPs on mutational sensitivity and stability of the encoded proteins. Taken together, we identified DNA polymorphisms having relevance in drought stress response and revealed candidate genes to engineer drought tolerance in chickpea. © 2021 Scandinavian Plant Physiology Society.

Physiologia Plantarum

Genome-wide discovery of DNA polymorphisms via resequencing of chickpea cultivars with contrasting response to drought stress

We evaluated the anti-leishmanial efficacy of different saturated medium-chain fatty acids (FAs, C8–C18) where FA containing C8 chain, caprylic acid (CA), was found to be most potent against Leishmania donovani, the causative agent for visceral leishmaniasis (VL). Different analogs of CA with C8 linear chain, but not higher, along with a carboxyl/ester group showed a similar anti-leishmanial effect. Ergosterol depletion was the major cause of CA-mediated cell death. Molecular docking and molecular dynamic simulation studies indicated the enzyme mevalonate kinase (MevK) of the ergosterol biosynthesis pathway as a possible target of CA. Enzyme assays with purified recombinant MevK and CA/CA analogs confirmed the target with a competitive inhibition pattern. Using biochemical and biophysical studies; strong binding interaction between MevK and CA/CA analogs was established. Further, using parasites with overexpressed MevK and proteomics studies of CA-treated parasites the direct role of MevK as the target was validated. We established the mechanism of the antileishmanial effect of CA, a natural product, against VL where toxicity and drug resistance with current chemotherapeutics demand an alternative. This is the first report on the identification of an enzymatic target with kinetic parameters and mechanistic insights against any organism for a natural medium-chain FA. © 2022, The Author(s).

Fulltext

Scientific Reports

Mechanistic insight into the role of mevalonate kinase by a natural fatty acid-mediated killing of Leishmania donovani

Th17 cells are essential for protection against extracellular pathogens, but their aberrant activity can cause autoimmunity. Molecular mechanisms that dictate Th17 cell-differentiation have been extensively studied using mouse models. However, species-specific differences underscore the need to validate these findings in human. Here, we characterized the human-specific roles of three AP-1 transcription factors, FOSL1, FOSL2 and BATF, during early stages of Th17 differentiation. Our results demonstrate that FOSL1 and FOSL2 co-repress Th17 fate-specification, whereas BATF promotes the Th17 lineage. Strikingly, FOSL1 was found to play different roles in human and mouse. Genome-wide binding analysis indicated that FOSL1, FOSL2 and BATF share occupancy over regulatory regions of genes involved in Th17 lineage commitment. These AP-1 factors also share their protein interacting partners, which suggests mechanisms for their functional interplay. Our study further reveals that the genomic binding sites of FOSL1, FOSL2 and BATF harbour hundreds of autoimmune disease-linked SNPs. We show that many of these SNPs alter the ability of these transcription factors to bind DNA. Our findings thus provide critical insights into AP-1-mediated regulation of human Th17-fate and associated pathologies. © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

Nucleic Acids Research

A systematic comparison of FOSL1, FOSL2 and BATF-mediated transcriptional regulation during early human Th17 differentiation

Bisphenol A (BPA) is a known endocrine disruptor with estrogen-like effects, which causes damage to human organs. BPA can affect the immune, reproductive, and neuroendocrine systems and is also carcinogenic. Herein, highly selective electrochemical sensing of BPA using H+-exchanged α-MnO2 in water under room conditions was developed. H+-exchanged α-MnO2 was synthesized via ion exchange. The synthesized material was characterized using an X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS), which confirms a successful synthesis of 1-D H+-exchanged α-MnO2. A nano-enabled, label-free electrochemical sensor was fabricated by employing synthesized materials. The sensor prominently showed high sensitivity of 0.64 kΩ/nM/mm2 and a lower limit of detection (LoD) of 16 nM. The equivalent Randel circuit was modeled for electron transfer kinetics evaluation. Additionally, the shelf life analysis confirmed the stability and reproducibility of the designed sensor over 30 days. Moreover, the sensor is highly selective toward BPA against other organic compounds. So, H+-exchanged α-MnO2-based BPA sensor provides a feasible and novel avenue to detect BPA in water under ambient conditions for health safety purposes. © 2001-2012 IEEE.

IEEE Sensors Journal

Enhanced Bisphenol A Sensing in Water Using 1-D H+Exchanged α-MnO2-Based Impedimetric Sensor

<p>Nematode parasites of the family Anisakidae infect definitive hosts, such as fish-eating birds and mammals, through primary intermediate hosts like copepods and secondary intermediate hosts like fishes. However, consumption of raw or undercooked fish can lead to nematode infection called anisakidosis in humans. We observed the presence of nematode infection in hillstream loaches of families Cobitidae and Nemacheilidae available for human consumption in the local markets in the northern parts of Western Ghats, India. Scanning electron micrograph and genetic identification employing mitochondrial cytochrome oxidase subunit II, identified the nematode to the genus Contracaecum. Histology of infected host revealed the presence of the parasite in muscles. Antioxidant enzyme analysis of host liver suggested that infection leads to oxidative stress in the fish. We suspect that a gradual increase in parasite infection of the loaches in the last decade could be attributed to various anthropogenic stressors that are altering riverine habitats. Since loaches are consumed by tribal people who often prepare the fish without degutting and possibly undercooked, there is a potential threat of human infection. © 2022 John Wiley &amp; Sons Ltd.</p>

Journal of Fish Diseases

Contracaecum nematode parasites in hillstream loaches of the Western Ghats, India

Ultra-thin diamond membranes, diamanes, are one of the most intriguing quasi-2D films, combining unique mechanical, electronic and optical properties. At present, diamanes have been obtained from bi- or few-layer graphene in AA- and AB-stacking by full hydrogenation or fluorination. Here, we study the thermal conductivity of diamanes obtained from bi-layer graphene with twist angle (Formula presented.) between layers forming a Moiré pattern. The combination of DFT calculations and machine learning interatomic potentials makes it possible to perform calculations of the lattice thermal conductivity of such diamanes with twist angles (Formula presented.) of 13.2 (Formula presented.), 21.8 (Formula presented.) and 27.8 (Formula presented.) using the solution of the phonon Boltzmann transport equation. Obtained results show that Moiré diamanes exhibit a wide variety of thermal properties depending on the twist angle, namely a sharp decrease in thermal conductivity from high for “untwisted” diamanes to ultra-low values when the twist angle tends to 30 (Formula presented.), especially for hydrogenated Moiré diamanes. This effect is associated with high anharmonicity and scattering of phonons related to a strong symmetry breaking of the atomic structure of Moiré diamanes compared with untwisted ones. © 2022 by the authors.

Physics

Membranes

Ultra-Low Thermal Conductivity of Moiré Diamanes

Room-temperature phosphorescence (RTP) from organic compounds has attracted increasing attention in the field of data security, sensing, and bioimaging. However, realization of RTP with an aggregate induced phosphorescence (AIP) feature via harvesting supersensitive excited charge transfer triplet (3CT) energy under visible light excitation (VLE) in single-component organic systems at ambient conditions remains unfulfilled. Organic donor-acceptor (D-A) based orthogonal structures can therefore be used to harvest the energy of the 3CT state at ambient conditions under VLE. Here we report three phenoxazine-quinoline conjugates (PQ, PQCl, PQBr), in which D and A parts are held in orthogonal orientation around the C-N single bond; PQCl and PQBr are substituted with halogens (Cl, Br) while PQ has no halogen atom. Spectroscopic studies and quantum chemistry calculations combining reference compounds (Phx, QPP) reveal that all the compounds in film at ambient conditions show fluorescence and green-RTP due to (i) radiative decay of both singlet charge transfer (1CT) and triplet CT (3CT) states under VLE, (ii) energetic nondegeneracy of 1CT and 3CT states (1CT- 3CT, 0.17-0.21 eV), and (iii) spatial separation of highest and lowest unoccupied molecular orbitals. Further, we found in a tetrahydrofuran-water mixture (fw = 90%, v/v) that both PQCl (10-5 M) and PQBr (10-5 M) show concentration-dependent AIP with phosphorescence quantum yields (φP) of ∼25% and ∼28%, respectively, whereas aggregate induced quenching (ACQ) was observed in PQ. The phosphorescence lifetimes (τP) of the PQCl and PQBr aggregates were shown to be ∼22-62 μs and ∼22-59 μs, respectively. The φP of the powder samples is found to be 0.03% (PQ), 15.6% (PQCl), and 13.0% (PQBr), which are significantly lower than that of the aggregates (10-5 M, fw = 90%, v/v). Film (Zeonex, 0.1 wt %) studies revealed that φP of PQ (7.1%) is relatively high, while PQCl and PQBr exhibit relatively low φP values (PQCl, 9.7%; PQBr, 8.8%), as compared with that of powder samples. In addition, we found in single-crystal X-ray analysis that multiple noncovalent interactions along with halogen···halogen (Cl···Cl) interactions between the neighboring molecules play an important role to stabilize the 3CT caused by increased rigidity of the molecular backbone. This design principle reveals a method to understand nondegeneracy of 1CT and 3CT states, and RTP with a concentration-dependent AIP effect using halogen substituted twisted donor-acceptor conjugates. © 2022 American Chemical Society. All rights reserved.

Chemistry

ACS Omega

Phenoxazine-Quinoline Conjugates: Impact of Halogenation on Charge Transfer Triplet Energy Harvesting via Aggregate Induced Phosphorescence

Alteration of transport properties of any material, especially metal oxides, by doping suitable impurities is not straightforward as it may introduce multiple defects like oxygen vacancies (Vo) in the system. It plays a decisive role in controlling the resistive switching (RS) performance of metal oxide-based memory devices. Therefore, a judicious choice of dopants and their atomic concentrations is crucial for achieving an optimum Voconfiguration. Here, we show that the rational designing of RS memory devices with cationic dopants (Ta), in particular, Au/Ti1-xTaxO2-δ/Pt devices, is promising for the upcoming non-volatile memory technology. Indeed, a current window of ∼104is realized at an ultralow voltage as low as 0.25 V with significant retention (∼104s) and endurance (∼105cycles) of the device by considering 1.11 at % Ta doping. The obtained device parameters are compared with those in the available literature to establish its excellent performance. Furthermore, using detailed experimental analyses and density functional theory (DFT)-based first-principles calculations, we comprehend that the meticulous presence of Voconfigurations and the columnar-like dendritic structures is crucial for achieving ultralow-voltage bipolar RS characteristics. In fact, the dopant-mediated Vointeractions are found to be responsible for the enhancement in local current conduction, as evidenced from the DFT-simulated electron localization function plots, and these, in turn, augment the device performance. Overall, the present study on cationic-dopant-controlled defect engineering could pave a neoteric direction for future energy-efficient oxide memristors. © 2022 American Chemical Society. All rights reserved.

ACS Applied Materials and Interfaces

Aliovalent Ta-Doping-Engineered Oxygen Vacancy Configurations for Ultralow-Voltage Resistive Memory Devices: A DFT-Supported Experimental Study

Ultrasmall MoS2 nanocrystals have unique optoelectronic and catalytic properties that have acquired significant attraction in many areas. We propose here a simple and economical method for synthesizing the luminescent nanocrystals MoS2 using the hydrothermal technique. In addition, the synthesized MoS2 nanocrystals display photoluminescence that is tunable according to size. MoS2 nanocrystals have many advantages, such as stable dispersion, low toxicity and luminescent characteristics, offering their encouraging applicability in biomedical disciplines. In this study, human lung cancer epithelial cells (A549) are used to assess fluorescence imaging of MoS2 nanocrystals. MTT assay, trypan blue assay, flow cytometry and fluorescence imaging results have shown that MoS2 nanocrystals can selectively target and destroy lung cancer cells, especially drug-resistant cells (A549). © 2022 Sahoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PLoS ONE

Cost-effective synthesis of 2D molybdenum disulfide (MoS2) nanocrystals: An exploration of the influence on cellular uptake, cytotoxicity, and bio-imaging