<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

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.

World University root node

Life Sciences

Nucleic Acids Research

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

Although pyridinic-nitrogen (pyri-N) doped graphene is highly active for the oxygen reduction reaction (ORR) of fuel cells in alkaline media, the activity critically decreases under acidic conditions. We report on how to prevent the deactivation based on the mechanistic understanding that (Formula presented.) governs the ORR kinetics. First, we considered that the deactivation is due to the hydration of pyri-NH+, leading to a lower shift of the redox potential. Introducing the hydrophobic cavity prevented the hydration of pyri-NH+ but inhibited the proton transport. We then increased proton conductivity in the hydrophobic cavity by introducing SiO2 particles coated with ionic liquid polymer/Nafion® which kept the high onset potentials with an increased current density even in acidic media. © 2022 Wiley-VCH GmbH.

Chemistry

Angewandte Chemie - International Edition

Activating Nitrogen-doped Graphene Oxygen Reduction Electrocatalysts in Acidic Electrolytes using Hydrophobic Cavities and Proton-conductive Particles

<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

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

Herein we have reported the discovery of a pentacyclic building block comprised of fused indole-quinoline and piperidinone from the natural product perophoramidine as a formidable anticancer agent. The compounds were synthesized in six steps where the key steps involved a blue LED mediated intramolecular cyclopropanation of the indole intermediates and concomitant reduction of the associated aryl nitro moiety to nitroso in the molecule. Cytotoxicity screening of the compounds against an array of cancer cells that is, MCF7, HCT116 and A549 demonstrated 0.6 to 9 μM IC50s by few of the compounds. γH2AX immunofluorescence assay of the two most potent molecules from the phenotypic screening with anti-γ-H2AX Alexa Fluor 488 antibody revealed extensive DNA damage of the A549 cells which indicated probable PARP inhibition (similar to Perophoramidine). Through molecular docking and molecular dynamic (MD) simulation studies the binding efficiency of our compounds with poly(ADP-ribose)polymerase 1 (PARP 1) enzyme was determined. Chemiluminescent PARP Assay with Histone-coated strips indicated that the most active compounds from the phenotypic screening induced PARP-1 inhibition with IC50s of 1.3→1.5 μM. © 2022 Wiley-VCH GmbH.

Chemistry - A European Journal

Capturing a Pentacyclic Fragment-Based Library Derived from Perophoramidine: Their Design, Synthesis and Evaluation as Anticancer Compounds by DNA Double-Strand Breaks (DSB) and PARP-1 Inhibition

Tuberculosis (TB) is a serious communicative disease caused by Mycobacterium tuberculosis. Although there are vaccines and drugs available to treat the disease, they are not efficient, moreover, multidrug-resistant TB (MDR-TB) become a major hurdle in its therapy. These MDR strains utilize the multidrug efflux pump as a decisive weapon to fight against antitubercular drugs. Tap membrane protein was observed as a crucial multidrug efflux pump in M. tuberculosis and its critical implication in MDR-MTB development makes it an effective drug target. In the present study, we have utilized various in silico approaches to predict the applicability of FDA-approved ion channel inhibitors and blockers as therapeutic leads against Tuberculosis by targeting multidrug efflux protein; Tap in MTB. Tap protein structure is predicted by Phyre2 server followed by model refinement, validation, physio-chemical catheterization and target prediction. Further, the interaction between Tap protein and ligands were analysed by molecular docking and MD simulation run of 100 ns. Based on implication and compatibility, 18 FDA-approved ion channel inhibitors and blockers are selected as a ligand against the Tap protein and eventually observed five ligands; Glimepiride, Flecainide, Flupiritine, Nimodipine and Amlodipine as promising compounds which have exhibited the significant stable interaction with Tap protein and are proposed to modulate or interfere with its activity. These compounds illustrated the substantial docking score and total binding enthalpy more than −7 kcal/mol and −42 kcal/mol respectively which implies that the selected FDA-approved compounds can spontaneously interact with the Tap protein to modulate its function. This study proposed Tap protein as a prominent drug target in MTB and investigated compounds that show considerable interaction with the Tap protein as potential therapeutic molecules. These interactions may lead to modulating or inhibit the activity of drug efflux protein thereby making MTB susceptible to antitubercular drugs. © 2022 Elsevier Ltd

Computers in Biology and Medicine

A multidrug efflux protein in Mycobacterium tuberculosis; tap as a potential drug target for drug repurposing

Wound healing is a complex phenomenon that requires coordination of numerous molecular and cellular changes to facilitate timely and efficient repair of the damaged tissue. Although many of these molecular pathways have been detailed, others remain to be elucidated. In the present work, we show for the first time, roles for the acetyltransferase TIP60 and nuclear receptor transcription factor PXR in this process, participating in wound healing by altering actin dynamics and cellular motility. We found that in response to wound-injury, TIP60 induces rapid formation of filopodia at the wounded cell front, leading to enhanced cell migration and faster closure of the wound. Further, qPCR analysis revealed heightened expression of Cdc42 and ROCK1 genes, key regulators involved in filopodia formation and actin reorganization, exclusively in TIP60-PXR-expressing cells upon wound-induction. We also performed ChIP assays to confirm the context-specific binding of TIP60 on the ROCK1 promoter and demonstrated that the TIP60 chromodomain is essential for loading of the TIP60–PXR complex onto the chromatin. Results from immunoprecipitation assays revealed that during the wounded condition, TIP60 alters the chromatin microenvironment by specifically acetylating histones H2B and H4, thereby modulating the expression of target genes. Overall, findings of this study show that TIP60 is a novel regulator of the wound healing process by regulating the expression of wound repair-related genes. © 2022 The Authors

Fulltext

Journal of Biological Chemistry

TIP60 acts as a regulator of genes involved in filopodia formation and cell migration during wound healing

In organic solar cells (OSCs), improving the properties at the interface of the bulk heterojunction (BHJ) photoactive layer and the buffer layer is desired, but achieving a high-quality interface between these two layers is inevitably challenging. Herein, a novel (PC61BM)-doped zinc oxide, that is, a (PC61BM-ZnO)DEZ hybrid thin film, is proposed for application as a cathode buffer layer (CBL) for OSCs based on both fullerene-based acceptors and nonfullerene acceptors. These thin films require low annealing temperatures and can be deposited via a one-step solution-processable method using a hybrid precursor composed of PC61BM and diethylzinc solution (DEZ). The study reveals that the performance of devices with (PC61BM-ZnO)DEZ hybrid thin films as a CBL exceeds that of devices with thin films of conventional ZnO as a CBL. Impedance analysis of the fabricated OSCs suggests improved charge collection efficiency in the devices with (PC61BM-ZnO)DEZ thin film. Optical, electrical, morphological, and compositional characterizations of thin films used as CBLs confirm the presence of a PC61BM-rich phase with traces of d-C61 (fullerene dimer) at the surface of the hybrid (PC61BM-ZnO)DEZ thin film. These phases help in tuning the interfacial properties by ensuring better coupling between the BHJ photoactive layer and the CBL. © 2022 Wiley-VCH GmbH.

Physics

Solar RRL

Investigating the Role of Cathode Buffer Layers Based on Zinc Oxide with Surface-Rich Graded Fullerene Isomers in Tuning the Interfacial Properties of Organic Solar Cells

Hydrogen peroxide plays a crucial role in the melanogenesis process by regulating the activity of the key melanin-forming enzyme tyrosinase, responsible for the browning of fruits, vegetables, and seafood. Therefore, a molecule with dual activities, both efficient tyrosinase inhibition and strong hydrogen peroxide degrading ability, may act as a promising antibrowning agent. Herein, we report highly efficient selone-based mushroom tyrosinase inhibitors 2 and 3 with remarkable glutathione peroxidase (GPx) enzyme-like activity. The presence of benzimidazole moiety enhances the tyrosinase inhibition efficiency of selone 2 (IC50= 0.4 μM) by almost 600 times higher than imidazole-based selone 1 (IC50= 238 μM). Interestingly, the addition of another aromatic ring to the benzimidazole moiety has led to the development of an efficient lipid-soluble tyrosinase inhibitor 3 (IC50= 2.4 μM). The selenium center and the -NH group of 2 and 3 are extremely crucial to exhibit high GPx-like activity and tyrosinase inhibition potency. The hydrophobic moiety of the inhibitors (2 and 3) further assists them in tightly binding at the active site of the enzyme and facilitates the C═Se group to strongly coordinate with the copper ions. Inhibitor 2 exhibited excellent antibrowning and polyphenol oxidase inhibition properties in banana and apple juice extracts. © 2022 American Chemical Society. All rights reserved.

Journal of Agricultural and Food Chemistry

Regulation of Tyrosinase Enzyme Activity by Glutathione Peroxidase Mimics

Chaotic mesoscopic cavities with ideal leads have been studied extensively using the powerful formalism of random matrix theory. Consequently, the statistical behavior of quantum transport observables, such as Landauer conductance and shot noise power, is fairly well understood. However, these have been explored far less in cavities with nonideal leads, i.e. having tunnel barriers. Here, we consider chaotic mesoscopic cavities with one ideal and one nonideal lead, and investigate the statistics of conductance and shot noise power under the condition of broken time-reversal symmetry. We derive exact expressions for the average and variance for both conductance and shot noise power. Moreover, we provide exact characteristic functions of these quantities, which are subsequently Fourier-inverted using a simple yet effective numerical procedure to obtain the corresponding distributions. We examine these quantities by varying the tunneling probabilities. We also compare our analytical results with Monte Carlo simulations and find very good agreements. © 2022 Elsevier B.V.