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Shiv Nadar University

(SoNS) School of Natural Sciences

Large collections of molecules (chemical libraries) are nowadays routinely screened in the process of designing drugs for specific ailments. Chemical and structural similarities between these molecules can be quantified using molecular descriptors, and these similarities can in turn be used to represent any chemical library as an undirected network called a chemical space network (CSN). Here we study different CSNs using conventional graph measures as well as random matrix theory (RMT). For the conventional graph measures, we focus on the average degree, average path length, graph diameter, degree assortativity, transitivity, average clustering coefficient and modularity. For the RMT analyses, we examine the eigenvalue spectra of adjacency matrices constructed from the molecular similarities for different CSNs, and examine their local fluctuation properties, contrasting them with the predictions of RMT. Changes in the conventional graph measures and RMT statistics with the network structure are examined for three different chemical libraries by varying the edge density (fraction of the actual to the maximum possible number of edges) of the networks. It is found that the assortativity among the conventional graph measures, and long-range fluctuation statistics of RMT in eigenvalue space respond to the changes in global network structure as well as the chemical space. We expect that this investigation of the network characteristics of different kinds of chemical libraries will provide guidance in the design of high-throughput screening libraries for different drug design applications. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Physics

Journal of Mathematical Chemistry

Investigation of chemical space networks using graph measures and random matrix theory

Life Sciences

Fulltext

Frontiers in Microbiology

Editorial: Plastic to Bioplastic (P2BP): A Green Technology for Circular Bioeconomy

The lack of a convenient method for the iterative generation of diverse full-length viral variants has impeded the study of directed evolution in RNA viruses. By integrating a full RNA genome error-prone PCR and reverse genetics, random genome-wide substitution mutagenesis can be induced. We have developed a method using this technique to synthesize diverse libraries to identify viral mutants with phenotypes of interest. This method, called full-length mutant RNA synthesis (FL-MRS), offers the following advantages: (i) the ability to create a large library via a highly efficient one-step error-prone PCR; (ii) the ability to create groups of libraries with varying levels of genetic diversity by manipulating the fidelity of DNA polymerase; (iii) the creation of a full-length PCR product that can directly serve as a template for mutant RNA synthesis; and (iv) the ability to create RNA that can be delivered into host cells as a non-selected input pool to screen for viral mutants of the desired phenotype. We have found, using a reverse genetics approach, that FL-MRS is a reliable tool to study viral-directed evolution at all stages in the life cycle of the hepatitis C virus, JFH1 isolate. This technique appears to be an invaluable tool to employ directed evolution to understand adaptation, replication, and the role of viral genes in pathogenesis and antiviral resistance in positive-sense RNA viruses. © 2022, Journal of Visualized Experiments. All rights reserved.

Journal of Visualized Experiments

Reverse Genetics to Engineer Positive-sense RNA Virus Variants

We investigate the (1 + 1)-dimensional position-dependent mass Dirac equation within the confines of so(2, 1) potential algebra by utilizing the character of a spatial varying Fermi velocity. We examine the combined effects of the two when the Dirac equation is equipped with an external pseudoscalar potential. Solutions of the three cases induced by so(2, 1) are explored by profitably making use of a point canonical transformation. © 2022 IOP Publishing Ltd.

Journal of Physics A: Mathematical and Theoretical

so(2, 1) algebra, local Fermi velocity, and position-dependent mass Dirac equation

Hirschsprung's disease (HD) is widely characterized by the absence of ganglion cells in the colon of infants and children resulting in a spectrum of diseases starting from constipation to intestinal obstruction. The disease can have a serious manifestation of Hirschsprung-associated enterocolitis which can lead to significant morbidity and even mortality. Presently the treatment includes surgical excision of the pathological segment of the colon. Identification of the segment requires histopathology and immunohistochemistry which is time-consuming and requires significant expertise of a pathologist. There is a gap in the management of the disease in the form of absence of suitable, sensitive, and efficient technologies to detect the pathological segment of the intestine, which could significantly reduce surgery duration in the operation theatre, as well as associated risks to patients. It, therefore, becomes a matter of extreme importance to develop a point-of-care platform for early and efficient identification of the occurrence of HD in neonates and older children during surgery. The present work reports on the development of an electrochemical enzymatic biosensor using anodized laser-induced graphene (aLIG) conjugated with acetylcholinesterase enzyme (AchE), for detection of HD as a function of acetylcholine – the key biomarker. The developed sensor was initially characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), while the sensor's analytical performance was assessed using CV. The sensor exhibited a limit of detection of 0.26 μM with a shelf life of 1 month, while remaining unperturbed in the presence of common interferants. The performance of the developed sensor was also examined in spiked serum samples and was observed to yield a high degree of linearity. © 2022 Elsevier B.V.

Diamond and Related Materials

Design and development of an electroanalytical enzymatic sensor using anodized laser induced graphene for the management of Hirschsprung Disease

This work reports a detailed and systematic theoretical study of the anisotropic thermoelectric properties of bulk Germanium Sulfide (GeS) in its orthorhombic Pnma phase. Density functional theory (DFT), employing the generalized gradient approximation (GGA), has been used to examine the structural and electronic band structure properties of bulk GeS. Electronic transport properties have been studied by solving semiclassical Boltzmann transport equations. A machine-learning approach has been used to estimate the temperature-dependent lattice part of thermal conductivity. The study reveals that GeS has a direct band gap of 1.20 eV. Lattice thermal conductivity is lowest along crystallographic a-direction, with a minimum of ∼0.98 Wm −1 K −1 at 700 K. We have obtained the maximum figure of merit (ZT) ∼ 0.73 at 700 K and the efficiency ∼7.86% in a working temperature range of 300 K-700 K for pristine GeS along crystallographic a-direction. © 2022 IOP Publishing Ltd.

Physica Scripta

A study of anisotropic thermoelectric properties of bulk Germanium Sulfide in its Pnma phase: a combined first-principles and machine-learning approach

Human COVID-19 has affected more than 491 million people worldwide. It has caused over 6.1 million deaths and has especially perpetrated a high number of casualties among the elderly and those with comorbid illnesses. COVID-19 triggers a pro-oxidant response, leading to the production of reactive oxygen species (ROS) as a common innate defense mechanism. However, ROS are regulated by a key enzyme called G6PD via the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which controls the generation and removal of ROS in a tissue-specific manner. Therefore, a deficiency of G6PD can lead to the dysregulation of ROS, which causes a severe inflammatory response in COVID-19 patients. This report highlights the G6PD dichotomy in the regulation of ROS and inflammatory responses, as well as its deficiency in severity among COVID-19 patients. © 2022 Future Medicine Ltd.

Future Microbiology

G6PD deficiency: imbalance of functional dichotomy contributing to the severity of COVID-19

A direct functionalization of numerous 1,4-quinones with various aryl boronic acids is reported under blue light-emitting diodes (LEDs). This reaction occurs at room temperature in an open flask without any catalysts, base, and oxidants in acetonitrile (ACN) and is scalable in grams. With diverse 1,4-quinones like 1,4-benzo-, naphtho-, anthra-, and 4-bromonaphthoquinones as substrates, facile cross coupling reactions occur with aryl and alkyl boronic acids without assistance from any photocatalysts. 2-Alkylated cyclohexene-1,4-diones were obtained when the 1,4-quinones were reacted with alkyl boronic acids under standard reaction conditions. However, slight warming of the reaction mixture afforded the desired alkylated 1,4-quinones. The reaction is believed to proceed through the blue LED-induced radical formation of the aryl rings assisted by the 1,4-quinones. © 2022 American Chemical Society. All rights reserved.

Chemistry

Journal of Organic Chemistry

Blue Light-Emitting Diode-Induced Direct C-H Functionalization of 1,4-Quinones with Aryl and Alkyl Boronic Acids

Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during Plasmodium falciparum invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein–protein interaction (PPI) network-based molecular machinery. Here, we used an integrated in silico analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in P. falciparum, predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP’s interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed via synergistic inhibition in P. falciparum invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion via glideosome assembly protein myosin A in P. falciparum. These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics. Copyright © 2022 Anam, Kumari, Mukherjee, Rex, Biswas, Maurya, Ravikumar, Gupta, Kushawaha, Sah, Chaurasiya, Singhal, Singh, Kaushik, Prasad, Pati, Ranganathan and Singh.

Frontiers in Cellular and Infection Microbiology

Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion

Colorectal cancer typically begins from a nonmalignant polyp formation in the large intestine that, over time, develops into colorectal cancer. The growth of benign polyps can be checked if detected in the early stages of the disease. Doctors usually recommend colonoscopy to average and high-risk individuals for colorectal cancer screening. Elevated carcinoembryonic antigen (CEA) is a broadly used biomarker for colorectal cancer. The genetic and epigenetic alteration of genes such as p53, BRAF, APC, and PIK3CA is also correlated with colorectal cancer in various clinical studies. In general, tissue biopsy is most frequently used for colorectal cancer diagnosis, but the whole tumor heterogeneity cannot be accessed by this technique. Furthermore, such a highly invasive technique is not suitable for repeated testing. Recently, extracellular vesicles (EVs), lipid bilayer enclosed sacs secreted from colorectal cancer cells, are emerging as a diagnostic tool for colon cancer detection. The major advantages of using EVs for colon cancer diagnosis are (i) EVs can be isolated in a noninvasive manner from the body fluid and (ii) EV incorporated cargoes (mostly RNAs) reveal various aspects of colorectal cancer. EV-RNAs are also implicated in tumor invasion and influence the immune system for the further spread of tumors. However, due to the lack of standardized EV detection strategies, diagnostic applicability is limited. Herein, we review the recent literature on the pathobiological dependence of colorectal cancer on EV-RNAs. Further, we present the advantages of identification and characterization of EV-RNAs to explore the connection between differential expression of extracellular vesicle incorporated RNAs and colorectal cancer. How this approach may potentially translate into point of care colorectal cancer diagnostics is also discussed. © 2022 by the Author(s).