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

The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created a global health crisis. The ability of vaccines to protect immunocompromised individuals and from emerging new strains are major concerns. Hence antiviral drugs against SARS-CoV-2 are essential. The SARS-CoV-2 main protease Mprois vital for replication and an important target for antivirals. Using CMap analysis and docking studies, withaferin A (wifA) and withanone (win), two natural products from the medicinal herb Withania somnifera (ashwagandha), were identified as promising candidates that can covalently inhibit the viral protease Mpro. Cell culture, enzymatic, LC-MS/MS, computational, and equilibrium dialysis based assays were performed. DFT calculations indicated that wifA and win can form stable adducts with thiols. The cytotoxicity of Mprowas significantly reduced by wifA and win. Both wifA and win were found to irreversibly inhibit 0.5 μM Mprowith IC50values of 0.54 and 1.8 μM, respectively. LC-MS/MS analysis revealed covalent adduct formation with wifA at cysteines 145 and 300 of Mpro. The natural products wifA and win can irreversibly inhibit the SARS-CoV-2 main protease Mpro. Based on the work presented here we propose that both wifA and win have the potential to be safely used as preventative and therapeutic interventions for COVID-19. © 2022 American Chemical Society. All rights reserved.

World University root node

(SoNS) School of Natural Sciences

Journal of Natural Products

The Natural Products Withaferin A and Withanone from the Medicinal Herb Withania somnifera Are Covalent Inhibitors of the SARS-CoV-2 Main Protease

The double-membrane-bound architecture of mitochondria, essential for ATP production, sub-divides the organelle into inter-membrane space (IMS) and matrix. IMS and matrix possess contrasting oxido-reductive environments and discrete protein quality control (PQC) machineries resulting inherent differences in their protein folding environments. To understand the nature of stress response elicited by equivalent proteotoxic stress to these sub-mitochondrial compartments, we took misfolding and aggregation-prone stressor proteins and fused it to well described signal sequences to specifically target and impart stress to yeast mitochondrial IMS or matrix. We show, mitochondrial proteotoxicity leads to growth arrest of yeast cells of varying degrees depending on nature of stressor proteins and the intra-mitochondrial location of stress. Next, by employing transcriptomics and proteomics, we report a comprehensive stress response elicited by stressor proteins specifically targeted to mitochondrial matrix or IMS. A general response to proteotoxic stress by mitochondria-targeted misfolded proteins is mitochondrial fragmentation, and an adaptive abrogation of mitochondrial respiration with concomitant upregulation of glycolysis. Beyond shared stress responses, specific signatures due to stress within mitochondrial sub-compartments are also revealed. We report that stress-imparted by bipartite signal sequence-fused stressor proteins to IMS, leads to specific upregulation of IMS-chaperones and TOM complex components. In contrast, matrix-targeted stressors lead to specific upregulation of matrix-chaperones and cytosolic PQC components. Finally, by systematic genetic interaction using deletion strains of differentially upregulated genes, we found prominent modulatory role of TOM complex components during IMS-stress response. In contrast, VMS1 markedly modulates the stress response originated from matrix. © 2022

Journal of Molecular Biology

Stress Responses Elicited by Misfolded Proteins Targeted to Mitochondria

Zootaxa

Diversity and distribution of dragon snakeheads of the family Aenigmachannidae, and the identity of Aenigmachanna mahabali

Tropical freshwater eels (Anguilla bengalensis and Anguilla bicolor) contribute a major share of the world's wild-caught eel production, having become the next major target owing to the declines in availability of both Anguilla japonica and Anguilla anguilla, species that have traditionally contributed to eel aquaculture and trade. Although both A. bengalensis and A. bicolor are assessed as Near Threatened on the International Union for Conservation of Nature Red List, these assessments are primarily based on anecdotal information and local knowledge on population declines. Demographics and exploitation levels of A. bengalensis and A. bicolor were determined from small coastal river systems, and their adjoining aquascapes in the Western Ghats hotspot of southern peninsular India, and the value of these data for future conservation planning discussed. The computed estimates of annual catch data for freshwater eels from the study region are between 0.17 (A. bicolor) to 0.30 t (A. bengalensis). Virtual population analysis of exploitation showed a drastic decline (in number) in the length groups >45 cm for both species, suggesting that they were less likely to attain their asymptotic length in the region. Current exploitation rates of A. bengalensis are unsustainable, and those for A. bicolor are almost close to reaching this level. Exploitation of all life stages from yellow eels to adults (29–171 cm) is likely to cause recruitment failure and significant mortality of spawning individuals of both species. An integrative conservation approach, including raising awareness (leading to voluntary restrictions), fishing closures in reservoirs, village-level quotas, and regular monitoring of populations, will ensure a sustainable future for the freshwater eel species in the Western Ghats hotspot, and elsewhere in the tropics where these species are exploited. © 2022 John Wiley & Sons Ltd.

Aquatic Conservation: Marine and Freshwater Ecosystems

Demographics and exploitation of two Near Threatened freshwater eels, Anguilla bengalensis and Anguilla bicolor, in small-scale subsistence fisheries and implications for conservation

Ephemeral rock pools are a characteristic type of aquatic habitat formed on the rock outcrops throughout the world, which harbor unique flora and fauna. Due to their structural simplicity and small size, rocky pools form a unique model ecosystem for studying how local environmental parameters shape aquatic vegetation. We studied the species-environment associations between the aquatic flora of the rock pools from the Western Ghats of India to understand whether species occurrence is influenced by the environmental parameters and whether we can predict the species occurrence using environmental variables. Sixty-one rock pools from 26 rock outcrops occupying different altitudinal gradients of the northern Western Ghats were sampled along with their physical properties and chemical characteristics. Canonical correspondence analysis suggested that altitude, latitude, magnesium, sulphate influenced species occurrence in rock pools. Replacement of species belonging to genus Eriocaulon across the altitudinal gradient was observed. Analysis of Covariance showed that most of the species are influenced by altitude while for few species both altitude and baserock were important. Application of various supervised learning procedures suggested that Random Forest was the most efficient method to predict species occurrence based on environmental parameters of rock pools. Decision trees based on Random Forest classification showed that multiple environmental factors including physical and chemical parameters of rock pools simultaneously influenced the species occurrence in the rock pools of the Western Ghats. © 2022 E. Schweizerbart’sche Verlagsbuchhandlung, Stuttgart, Germany.

Fundamental and Applied Limnology

Environmental determinants of aquatic vegetation in rock pools of northern Western Ghats, India

Mg-Co-Zn nanoferrites of composition MgxCo0.5Zn0.5Fe2−xO4 (x = 0.25, 0.5, 0.75 and 1.0) were successfully synthesized by using a citrate precursor method. After synthesis, the samples were examined using different techniques for structural, morphological, electrical and dielectric characterizations. All the samples were found to have single phase spinel cubic structure with Fd-3m space group in the X-ray diffraction spectroscopy (XRD) investigation. The value of average crystallite size ranged from 37 to 47 nm with the increase in Mg ion concentration from x = 0.25 to 1.0. The hopping lengths at tetrahedral and octahedral sites showed an increasing behaviour with increasing magnesium ion concentration. The presence of tensile strain in the samples was confirmed by W-H plots. The dielectric behaviour of the prepared nanoferrites was recorded at room temperature in the frequency range 10 kHz–10 MHz. The real part and imaginary part of the dielectric constant were found to be in the range 3.80–7.93 and 0.0036–0.644 at 1 MHz frequency and the value of loss tangent was 0.00095–0.081 at 1 MHz for the magnesium doped Co-Zn nanoferrites. The value of loss tangent decreased very sharply to remarkably low values at 10 MHz frequency. The dc resistivity value was found very low in the range 3.2 × 108 Ω-cm to 4.0 × 109 Ω-cm for different concentrations of Mg2+ ions in the samples. Due to such low losses at high frequency region and high value of dc resistivity, these materials can be considered as potential candidate for high frequency applications. © 2021 Elsevier B.V.

Journal of Magnetism and Magnetic Materials

Influence of Mg doping on the structural, electrical and dielectric properties of Co-Zn nanoferrites

Large-scale transcriptome analysis can provide a systems-level understanding of biological processes. To accelerate functional genomic studies in chickpea, we perform a comprehensive transcriptome analysis to generate full-length transcriptome and expression atlas of protein-coding genes (PCGs) and long non-coding RNAs (lncRNAs) from 32 different tissues/organs via deep sequencing. The high-depth RNA-seq dataset reveal expression dynamics and tissue-specificity along with associated biological functions of PCGs and lncRNAs during development. The coexpression network analysis reveal modules associated with a particular tissue or a set of related tissues. The components of transcriptional regulatory networks (TRNs), including transcription factors, their cognate cis-regulatory motifs, and target PCGs/lncRNAs that determine developmental programs of different tissues/organs, are identified. Several candidate tissue-specific and abiotic stress-responsive transcripts associated with quantitative trait loci that determine important agronomic traits are also identified. These results provide an important resource to advance functional/translational genomic and genetic studies during chickpea development and environmental conditions. © 2022, The Author(s).

Fulltext

Communications Biology

An integrated transcriptome mapping the regulatory network of coding and long non-coding RNAs provides a genomics resource in chickpea

Mitochondrial functions are heavily influenced by acid-base homeostasis. Hence, elucidation of the mitochondrial pH is essential in living cells, and its alterations during pathologies is an interesting question to be addressed. Small molecular fluorescent probes are progressively applied to quantify the mitochondrial pH by fluorescence imaging. Herein, we designed a unique small molecular fluorescent probe, PM-Mor-OH, based on the lipophilic morpholine ligand-conjugated pyridinium derivative of "IndiFluors". The morpholine-conjugated fluorescent probe usually localized the lysosome. However, herein, we observed unusual phenomena of morpholine-tagged PM-Mor-OH that localized mitochondria explicitly. The morpholine ligand also plays a pivotal role in tuning optical properties via photoinduced electron transfer (PET) during internal pH alteration (ΔpHi). In the mitophagy process, lysosomes engulf damaged mitochondria, leading to ΔpHi, which can be monitored using our probe. It exhibited "ratiometric"emission at single wavelength excitation (ex. 488) and is suitable for monitoring and quantifying the ΔpHi using confocal microscope high-resolution image analysis during mitophagy. The bathochromic emission shifts due to intramolecular charge transfer (ICT) in basic pH were well explained by the time-dependent density functional theory (TD-DFT/PCM). Similarly, the change in the emission ratio (green/red) with pH variations was also validated by the PET process. In addition, PM-Mor-OH can quantify the pH change during oxidative stress induced by rapamycin, mutant A53T α-synuclein-mediated protein misfolding stress in mitochondria, and during starvation. Rapamycin-induced mitophagy was further elucidated by the translocation of mCherry Parkin to damaged mitochondria, which well correlates with our probe. Thus, PM-Mito-OH is a valuable probe for visualizing mitophagy and can act as a suitable tool for the diagnosis of mitochondrial diseases. © 2022 American Chemical Society.

Chemistry

Analytical Chemistry

PET- and ICT-Based Ratiometric Probe: An Unusual Phenomenon of Morpholine-Conjugated Fluorophore for Mitochondrial pH Mapping during Mitophagy

The human innate immune system eliminates invading pathogens through phagocytosis. The first step of this process is activating the nicotinamide adenine dinucleotide phosphate oxidase (Nox2) that utilizes NADPH to produce superoxide anion radicals and other reactive oxygen species (ROS). These ROS then alter the mitochondrial membrane potential and increase peroxide in the mitochondria. The peroxide reacts with myeloperoxidase (MPO) and chloride ions to produce pro-inflammatory oxidant hypochlorous acid (HOCl), which causes oxidative stress leading to cell death. The adverse effects of HOCl are highly associated with cardiovascular disease, neurodegenerative disorders, acute lung injuries, inflammatory diseases, and cancer. Therefore, mapping HOCl in the Nox2 pathway is crucial for an in-depth understanding of the innate immune system. Herein, we developed a unique pentacyclic pyridinium probe, PM-S, that exhibited efficient photoinduced electron transfer (PeT) with HOCl triggered methyl(phenyl)sulfane. PM-S showed several advantages, including better chemical stability, large Stokes shifts (&gt;6258 cm−1), high sensitivity (∼50 nM) and specificity to mitochondria, compared to its parent pyrylium PY-S derivative. This probe is also efficient in studying the HOCl produced via the Nox2 pathway in HepG2 and HeLa cells. Analysis using a simple microplate reader and FACS analysis with various inhibitors and inducers supported the mechanistic understanding of Nox2, which can offer an advanced platform for monitoring the inflammatory process more efficiently. © 2022 The Royal Society of Chemistry

Journal of Materials Chemistry B

An efficient PeT based fluorescent probe for mapping mitochondrial oxidative stress produced via the Nox2 pathway

We report the synthesis of Ca-doped Mg–Zn ferrite Mg0.4Zn(0.6-x)CaxFe2O4 nanomaterials with x = 0, 0.1, 0.2, 0.3, 0.4, 0.5, and 0.6 through citrate precursor approach and their structural, morphological, optical, photocatalytic, and antimicrobial properties were systematically studied. The prepared nanoferrites's cubic spinel structure with an average crystallite size of 15–38 nm was evaluated by the XRD examination. The spherical morphology of these ferrite nanoparticles was seen from scanning electron microscopy (SEM). The observed bands at 560 cm−1 and 406 cm−1 in the FTIR spectra confirmed the spinel structure of the synthesized nanoferrite. The optical study confirmed an optical band gap of 1.60 eV–1.86 eV. The photocatalysis was done for the degradation of rhodamine B dye solution under UV light. All the synthesized nano ferrites displayed a promising antimicrobial potential upon Candida albicans fungi. Mg0.4Zn0.1Ca0.5Fe2O4 nanoparticles have a better photocatalytic response (99.5%) for the degradation of rhodamine B dye and show superior antimicrobial activity (96.1%) for the inhibition of Candida albicans fungi. © 2022 Elsevier Ltd and Techna Group S.r.l.