<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

Glioblastoma multiforme is known as the primary malignant and most devastating form of tumor in central nervous system of adult population. Amongst all CNS cancers, Glioblastoma multiforme GBM is a rare grade IV astrocytoma and it has the worst prognosis initiated by metastasis to supra-tentorial region of the brain. Current options for the treatment include surgery, radiation therapy and chemotherapy. Substantial information of its pathology and molecular signaling exposed new avenues for generating innovative therapies. In our study, we have undertaken a novel combination approach for GBM treatment. PI3K signaling participates in cancer progression and plays a significant role in metastasis. Here, we are targeting PI3K signaling pathways in glioblastoma along with EZH2, a known transcriptional regulator. We found that targeting transcriptional regulator EZH2 and PI3K affect cellular migration and morphological changes. These changes in signatory activities of cancerous cells led to inhibit its progression in vitro. With further analysis we confirmed the angiogenic inhibition and reduction in stem-ness potential of GBM. Later, cytokine proteome array analysis revealed several participants of metastasis and tumor induced angiogenesis using combination regime. This study provides a significant reduction in GBM progression investigated using Glioblastoma Multiforme U-87 cells with effective combination of pharmacological inhibitors PI-103 and EPZ-6438. This strategy will be further used to combat GBM more innovatively along with the existing therapies. Copyright: © 2020 Mishra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Life Sciences

Fulltext

Oncotarget

Amalgamation of PI3K and EZH2 blockade synergistically regulates invasion and angiogenesis: Combination therapy for glioblastoma multiforme

The pore forming Plasmodium Perforin Like Proteins (PPLP), expressed in all stages of the parasite life cycle are critical for completion of the parasite life cycle. The high sequence similarity in the central Membrane Attack Complex/ Perforin (MACPF) domain among PLPs and their distinct functional overlaps define them as lucrative target for developing multi-stage antimalarial therapeutics. Herein, we evaluated the mechanism of Pan-active MACPF Domain (PMD), a centrally located and highly conserved region of PPLPs, and deciphered the inhibitory potential of specifically designed PMD inhibitors. The E. coli expressed rPMD interacts with erythrocyte membrane and form pores of ~10.5 nm height and ~24.3 nm diameter leading to hemoglobin release and dextran uptake. The treatment with PMD induced erythrocytes senescence which can be hypothesized to account for the physiological effect of disseminated PLPs in loss of circulating erythrocytes inducing malaria anemia. The anti-PMD inhibitors effectively blocked intraerythrocytic growth by suppressing invasion and egress processes and protected erythrocytes against rPMD induced senescence. Moreover, these inhibitors also blocked the hepatic stage and transmission stage parasite development suggesting multi-stage, transmission-blocking potential of these inhibitors. Concievably, our study has introduced a novel set of anti-PMD inhibitors with pan-inhibitory activity against all the PPLPs members which can be developed into potent cross-stage antimalarial therapeutics along with erythrocyte senescence protective potential to occlude PPLPs mediated anemia in severe malaria. © Copyright © 2020 Garg, Shivappagowdar, Hada, Ayana, Bathula, Sen, Kalia, Pati, Singh and Singh.

Chemistry

World University root node

Frontiers in Cellular and Infection Microbiology

Plasmodium Perforin-Like Protein Pores on the Host Cell Membrane Contribute in Its Multistage Growth and Erythrocyte Senescence

Frontiers in Endocrinology

Editorial: Resistance to Endocrine Therapies in Cancer

Cystatins are classical competitive inhibitors of C1 family cysteine proteases (papain family). Phytocystatin superfamily shares high sequence homology and typical tertiary structure with conserved glutamine-valine-glycine (Q-X-V-X-G) loop blocking the active site of C1 proteases. Here, we develop a cysteine-bounded cyclic peptide (CYS-cIHL) and linear peptide (CYS-IHL), using the conserved inhibitory hairpin loop amino acid sequence. Using an in silico approach based on modeling, protein–peptide docking, molecular dynamics simulations and calculation of free energy of binding, we designed and validated inhibitory peptides against falcipain-2 (FP-2) and -3 (FP-3), cysteine proteases from the malarial parasite Plasmodium falciparum. Falcipains are critical hemoglobinases of P. falciparum that are validated targets for the development of antimalarial therapies. CYS-cIHL was able to bind with micromolar affinity to FP-2 and modulate its binding with its substrate, hemoglobin in in vitro and in vivo assays. CYS-cIHL could effectively block parasite growth and displayed antimalarial activity in culture assays with no cytotoxicity towards human cells. These results indicated that cyclization can substantially increase the peptide affinity to the target. Furthermore, this can be applied as an effective strategy for engineering peptide inhibitory potency against proteases. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Journal of Biomolecular Structure and Dynamics

Cyclic peptide engineered from phytocystatin inhibitory hairpin loop as an effective modulator of falcipains and potent antimalarial

Seed development is orchestrated via complex gene regulatory networks and pathways. Epigenetic factors may also govern seed development and seed size/weight. Here, we analyzed DNA methylation in a large-seeded chickpea cultivar (JGK 3) during seed development stages. Progressive gain of CHH context DNA methylation in transposable elements (TEs) and higher frequency of small RNAs in hypermethylated TEs during seed development suggested a role of the RNA-dependent DNA methylation pathway. Frequency of intragenic TEs was higher in CHH context differentially methylated region (DMR) associated differentially expressed genes (DEGs). CG context hyper/hypomethylation within the gene body was observed for most of DMR-associated DEGs in JGK 3 as compared to small-seeded chickpea cultivar (Himchana 1). We identified candidate genes involved in seed size/weight determination exhibiting CG context hypermethylation within the gene body and higher expression in JGK 3. This study provides insights into the role of DNA methylation in seed development and seed size/weight determination in chickpea. © 2020, The Author(s).

Communications Biology

DNA methylation reprogramming during seed development and its functional relevance in seed size/weight determination in chickpea

Methylation of cytosines in DNA is the most stable type of epigenetic modification that is established and maintained by different enzymes. In plants, DNA methylation is inherited from one generation to another leaving an epigenetic mark as a memory of previous state, which may include encounter with stress or pathogen. Advancement in the next generation sequencing technologies has enabled the profiling of methylation marks. Whole-genome bisulfite sequencing (WGBS) has the potential to unravel the patterns of DNA methylation at single-base resolution. Though the sequencing technologies have evolved drastically, analysis of WGBS data still remains challenging. Here, we provide a methodology for performing WGBS data analysis along with critical steps for identification of methylation marks in plant genomes including legumes. © Springer Science+Business Media, LLC, part of Springer Nature 2020.

Methods in Molecular Biology

Method for bisulfite sequencing data analysis for whole-genome level DNA methylation detection in legumes

(SoE) School of Engineering

(SME) School of Management and Entrepreneurship

Preface

Scalable production of high-quality MoS2 nanosheets remains challenging for industrial applications and research in basic sciences. N-methyl-2pyrrolidine (NMP) is a commonly used solvent for exfoliation of MoS2 nanosheets having further disadvantage of slow volatility rate. The present study demonstrates a cost-effective facile chemical route to synthesize few-layer MoS2 nanosheets using acetone as a solvent and by varying bulk initial concentration of samples to scale up the production in large scale to fulfill the demand for potential applications. In our study, we aim to obtain stable growth of high quality few layer MoS2 nanosheets by long sonication times. Optical absorption spectra, Raman spectra, size of nanosheets and layer thickness of as-grown MoS2 nanosheets were found to be matching with those obtained from other synthesis methods. Effective photocatalytic performance of MoS2 nanosheets without being consumed as a reactant was experimented by decomposing Methylene Blue dye in aqueous solution under irradiation of visible light. This study provides an idea to synthesize low-cost, sustainable and efficient photocatalytic material in large scale for the next generation to control water pollution quite efficiently by protecting the environment from the contamination coming from these dyes. © 2020, The Author(s).

Physics

Scientific Reports

Cost effective liquid phase exfoliation of MoS2 nanosheets and photocatalytic activity for wastewater treatment enforced by visible light

Thin films of β-W are the most interesting for manipulating magnetic moments using spin–orbit torques, and a clear understanding of α to β phase transition in W by doping impurity, especially oxygen, is needed. Here we present a combined experimental and theoretical study using grazing incidence X-ray diffraction, photoelectron spectroscopy, electron microscopy, and ab initio calculations to explore atomic structure, bonding, and oxygen content for understanding the formation of β-W. It is found that the W films on SiO2/Si have 13–22 at.\% oxygen in A15 β structure. Ab initio calculations show higher solution energy of oxygen in β-W, and a tendency to transform locally from α to β phase with increasing oxygen concentration. X-ray absorption spectroscopy also revealed local geometry of oxygen in β-W, in agreement with the simulated one. These results offer an opportunity for a fundamental understanding of the structural transition in α-W and further development of β-W phase for device applications. © 2020, The Author(s).

Center for Informatics

Unravelling oxygen driven α to β phase transformation in tungsten

Olefin bonds participate in co-reaction with the benzoxazine functionality of the monomer and are one of the strategies used to affect the crosslink density of a polybenzoxazine network. In general, the double bond incorporation in starting material is usually catalyzed by expensive, rare earth metals affecting the sustainability of the reaction. The natural abundance of feedstocks with inherent double bonds may be a powerful platform for the development of novel greener structures, with potential applications in polymers. Here, we report the design, synthesis, and characterization of a biobased non-halogen flame retardant, consisting of naturally occurring phenols, eugenol (E), and cardanol (C). The presence of a covalently linked phosphazene (P) core allowed the synthesis of hexa-functional flame retardant molecules, abbreviated as EP and CP. The chemical structures of the synthesized EP and CP were confirmed by Fourier transform infrared (FTIR), nuclear magnetic resonance (1H, 13C, 31P NMR), and single crystal XRD (only in the case of EP). Their polymerization with cardanol sourced tri-oxazine benzoxazine monomer, C-trisapm, was followed by FTIR, NMR, and DSC studies. The thermal stability and flame retardant properties of the hybrid phosphazene-benzoxazine copolymers was determined by thermogravimetry analysis (TGA), limiting oxygen index (LOI), vertical burning, and smoke density analyses. SEM images of the char residues of the polymers with or without the addition of reactive phosphazene molecules confirmed the intumescent flame retarding mechanism. Current work highlights the utility of sustainable origin non-halogen flame retardant (FR) molecules and their utility in polybenzoxazine chemistry. © Copyright © 2020 Appavoo, Amarnath and Lochab.