Publications by authors named "Nitin Khandelwal"

37 Publications

Effect of clay colloid - CuO nanoparticles interaction on retention of nanoparticles in different types of soils: role of clay fraction and environmental parameters.

Environ Res 2021 Aug 12;203:111885. Epub 2021 Aug 12.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research Kolkata, Kolkata, Mohanpur, West Bengal, 741246, India; Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, 741246, India. Electronic address:

The extensive application of metal oxide nanoparticles (NPs) in various sectors has raised concern about their subsequent release and potentially harmful impacts on the soil system. The present study has addressed the interaction of CuO NPs with bentonite clay colloids (CC) under varying environmental parameters as a model to represent the soil pore water scenario. Based on CuO - CC interaction in model and natural soil solution extracts (SSE), the role of clay fraction and their stability on CuO retention in various types of soils have been evaluated. Results suggested that increasing ionic strength (IS) in the system caused aggregation of CuO NPs, and in the presence of CC, critical coagulation concentration decreased drastically from 27.8 and 17.3 mM to 10.7 and 0.33 mM for NaCl and CaCl respectively, due to heteroaggregation in the system. Interestingly, in the SSE, the dominating role of ionic valency, dissolved organic carbon (DOC), and CC was observed in colloidal stabilization over IS. No significant impact of temperature was observed on the stability of CuO NPs both in model and SSE. Further, stability studies in the SSE were correlated with NPs retention behavior in soils. Observations suggest that retention of CuO NPs in soils is a function of binding of the colloidal fraction to the soil, which in turn depends on the colloidal stability. The highest retention was observed in black and laterite soils, whereas lower binding of clay fraction in red soil caused the least retention. A decrease in K values after a certain application concentration provided maximum sustainable application concentration of CuO NPs, which may vary with soil properties. Results suggest that the binding of clay and organic matter with a sandy matrix of soil plays a prime role in deciding the overall fate of CuO NPs in the soils.
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http://dx.doi.org/10.1016/j.envres.2021.111885DOI Listing
August 2021

Biochar-facilitated remediation of nanoplastic contaminated water: Effect of pyrolysis temperature induced surface modifications.

J Hazard Mater 2021 Sep 18;417:126096. Epub 2021 May 18.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur, West Bengal 741246, India; Centre for Climate and Environmental Studies, Indian Institute of Science Education, and Research, Kolkata, Mohanpur, West Bengal 741246, India. Electronic address:

"Nanoplastics- the emerging contaminants" and "agricultural waste to resource conversion" both are currently at the scientific frontiers and require solutions. This study aims to utilize sugarcane bagasse-derived biochar for the removal of nanoplastics (NPs) from aqueous environment. Three types of biochar were synthesized at three different pyrolysis temperatures, i.e. 350, 550, and 750 ℃ and evaluated for their potential in removing NPs. Effect of various environmental parameters, i.e., competing ions, pH, humic acid and complex aqueous matrices on NPs sorption was also studied. Results showed that attributing to decreased carbonyl functional groups, increased surface area and pore abundance, biochar prepared at 750 ℃ showed drastically higher NPs removal (>99%), while BC-550 and BC-350 showed comparatively lower NPs sorption (<39% and <24%, respectively). Further sorption studies confirmed instantaneous NPs removal with equilibrium attainment within 5 min of interaction and efficient NPs sorption capacity, i.e. 44.9 mg/g for biochar prepared at 750 ℃. Non-linear-kinetic modeling suggested pseudo 1st order removal kinetics while isotherm and thermodynamic modeling confirmed- monolayer instantaneous sorption of NPs sorption. Enhanced electrostatic repulsion resulted in decrease in NPs sorption at alkaline conditions, whereas steric hindrance caused limited removal (<25%) at higher humic acid concentrations.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126096DOI Listing
September 2021

Combined antioxidant capped and surface supported redox-sensitive nanoparticles for continuous elimination of multi-metallic species.

Chem Commun (Camb) 2021 Jul 2;57(59):7280-7283. Epub 2021 Jul 2.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal 741246, India.

A strategic modification involving (i) a multi-functional almond shell biochar surface support and (ii) capping with almond skin extracted antioxidants was performed to preserve redox-sensitive Fe nanoparticles (NPs). pXRD data showed generation of an iron-carbonyl shell on the supported Fe NPs (SA-Fe), justifying successful antioxidant capping. The total metal removal capacity of 695 mg gi.e. AsO (300.2 mg g) > Cd (224.2 mg g) > CrO (125.2 mg g) > Ni (44.5 mg g) in batch mode, and 102 mg g in continuous column setup confirms the excellent reactivity of the SA-Fe nanocomposite. Loss of the iron-carbonyl shell and iron oxidation during interaction with contaminants confirm no hindrance in electron transfer due to antioxidant capping.
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http://dx.doi.org/10.1039/d1cc02972jDOI Listing
July 2021

A decade of exploring MXenes as aquatic cleaners: Covering a broad range of contaminants, current challenges and future trends.

Chemosphere 2021 Sep 16;279:130587. Epub 2021 Apr 16.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur, West Bengal, India, 741246; Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur, West Bengal, 741246, India. Electronic address:

Clean water, the elixir of life, is of tremendous importance in achieving environmental sustainability and the balanced functioning of our ecosystem. Coupled with population growth, several anthropogenic activities and environmental catastrophes have together contributed to an alarming increase in the concentration of toxic pollutants in water bodies. Diversified physiochemical conditions of water matrices, ranging from mining drainage to seawater, is the critical challenge in designing adsorbents. MXenes, a new class of 2D layered materials, are transition metal nitrides, carbides, carbonitrides or borides formed through selective etching process. MXenes are known to have high surface area and activity with biological compatibility and chemical stability and therefore are promising adsorbents and have been explored for a broad range of contaminants. This review starts with a brief about environmental contaminants followed by synthesis and modifications of MXenes. It then revolves around their so far explored adsorbing and degradation properties for different contaminants ranging from toxic metals, inorganic ions, and radionuclides to various organic pollutants, including dyes, pharmaceuticals, aromatic hydrocarbons, and pesticides, etc. Finally, we have discussed associated toxicity, secondary contamination, future trends, and challenges in ascertaining scalability and wide-range applicability of MXenes in natural environmental conditions to make them a warrior of water sustainability.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130587DOI Listing
September 2021

Removal of chromate ions from leachate-contaminated groundwater samples of Khan Chandpur, India, using chitin modified iron-enriched hydroxyapatite nanocomposite.

Environ Sci Pollut Res Int 2021 Aug 31;28(31):41760-41771. Epub 2021 Mar 31.

Institute of Geosciences, Applied Geology, Friedrich-Schiller-Universitat Jena, Burgweg 11, D-07749, Jena, Germany.

Chromite ore processing residues (COPR) are real environmental threats, leading to CrO, i.e., Cr (VI) leaching into groundwater. It is of serious concern as Cr (VI) is proven to be carcinogenic. Here we emphasize the application of novel and eco-friendly chitin functionalized iron-enriched hydroxyapatite nanocomposite (HAP-Fe-Ct) in the remediation of Cr (VI)-contaminated groundwater samples collected from Khan Chandpur, India, where the level of Cr (VI) is found to be 11.7 mg/L in a complex aqueous matrix having 793 mg/L of total dissolved solids. Chitin functionality in the composite has resulted in positive zeta potential at circum-neutral pH, favoring electrostatic attraction of chromate ions and resulting in its bulk surface transport. The HAP-Fe-Ct showed faster kinetics of removal with efficiency (q = 13.9 ± 0.46 mg/g) for Cr (VI). The composite has shown sorption equilibrium and 100% removal of Cr (VI) within 3 h of interaction time in groundwater samples. No Cr (VI) leaching in the acid wash process at pH 3.5 also suggests chromium's strong chemisorption onto nanocomposite. During the interaction in aqueous solutions, the reduced iron (Fe) on the nanocomposite becomes oxidized, suggesting the probable simultaneous reduction of Cr (VI) and its co-precipitation. Continuous column extraction of chromate ions was also efficient in both spiked solutions (39.7 ± 0.04 mg/g) and COPR contaminated water (13.2 ± 0.09 mg/g). Reusability up to three cycles with almost complete Cr (VI) removal may be attributed to surface protonation, new binding sites generation, and electron transfer from Fe core through defects. The study concludes that HAP-Fe-Ct could be utilized for continuous Cr (VI) removal from COPR contaminated complex groundwater matrices.
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http://dx.doi.org/10.1007/s11356-021-13549-7DOI Listing
August 2021

Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E.

Antiviral Res 2021 05 10;189:105056. Epub 2021 Mar 10.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India. Electronic address:

Emetine is a FDA-approved drug for the treatment of amebiasis. Previously we demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. In this study, we evaluated the in vitro antiviral efficacy of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and found it to be a low nanomolar (nM) inhibitor. Interestingly, emetine exhibited protective efficacy against lethal challenge with infectious bronchitis virus (IBV; a chicken coronavirus) in the embryonated chicken egg infection model. Emetine treatment led to a decrease in viral RNA and protein synthesis without affecting other steps of viral life cycle such as attachment, entry and budding. In a chromatin immunoprecipitation (CHIP) assay, emetine was shown to disrupt the binding of SARS-CoV-2 mRNA with eIF4E (eukaryotic translation initiation factor 4E, a cellular cap-binding protein required for initiation of protein translation). Further, molecular docking and molecular dynamics simulation studies suggested that emetine may bind to the cap-binding pocket of eIF4E, in a similar conformation as m7-GTP binds. Additionally, SARS-CoV-2 was shown to exploit ERK/MNK1/eIF4E signalling pathway for its effective replication in the target cells. Collectively our results suggest that further detailed evaluation of emetine as a potential treatment for COVID-19 may be warranted.
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http://dx.doi.org/10.1016/j.antiviral.2021.105056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943376PMC
May 2021

Gene Expression Analysis Identifies Cholesterol Metabolism Dysregulation in Hippocampus of Phenytoin-Resistant Pentylenetetrazol-Kindled Epileptic Mice.

Neuromolecular Med 2021 Feb 18. Epub 2021 Feb 18.

Epigenetics & Neuropsychiatric Disorders Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Habsiguda, Hyderabad, Telangana State, 500007, India.

Pharmaco-resistant Epilepsy has been a major challenge for medical interventions in controlling seizures. To date, up to 33% of the patients with epilepsy do not show adequate response to anti-epileptic drugs even after prolonged combinatorial drug usage. Using microarray, this study explores the changes in hippocampal gene expression in the phenytoin-resistant pentylenetetrazol (PTZ)-kindled mouse model of epilepsy. Our results from mRNA microarray analysis show distinct gene expression profiles in the hippocampus of phenytoin-resistant and sensitive mice. Pathway enrichment analysis showed differential expression of genes involved in cholesterol biosynthesis in phenytoin-resistant and sensitive mice.
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http://dx.doi.org/10.1007/s12017-021-08648-0DOI Listing
February 2021

Characteristics and spatial distribution of microplastics in the lower Ganga River water and sediment.

Mar Pollut Bull 2021 Feb 13;163:111960. Epub 2021 Jan 13.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, West Bengal, India; Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, West Bengal, India. Electronic address:

Although India is one of the major plastic-waste-generating countries, few studies have been conducted on microplastics (MPs) in freshwater systems that are key contributors to oceans. The current study explores MPs in sediments and water that were collected at five major cities across the Ganga River. MPs number and mass density range in sediment were found to be 17 to 36 items/kg dry weight (d.w.) and 10 to 45 mg/kg d.w. of sediments, respectively, while in the water sample, they were 380 to 684 items/1000 m and 143 to 340 mg/1000 m, respectively. Overall, white color and film-shaped MPs were the major contributors in all samples. MPs of 2.5-5 mm size contributed to a greater number and mass as compared to other fractions. Polyethylene was found to be a widely distributed plastic-type reflecting its high usability.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111960DOI Listing
February 2021

Role of p38 mitogen-activated protein kinase signalling in virus replication and potential for developing broad spectrum antiviral drugs.

Rev Med Virol 2021 Jan 15. Epub 2021 Jan 15.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, Haryana, India.

Mitogen-activated protein kinases (MAPKs) play a key role in complex cellular processes such as proliferation, development, differentiation, transformation and apoptosis. Mammals express at least four distinctly regulated groups of MAPKs which include extracellular signal-related kinases (ERK)-1/2, p38 proteins, Jun amino-terminal kinases (JNK1/2/3) and ERK5. p38 MAPK is activated by a wide range of cellular stresses and modulates activity of several downstream kinases and transcription factors which are involved in regulating cytoskeleton remodeling, cell cycle modulation, inflammation, antiviral response and apoptosis. In viral infections, activation of cell signalling pathways is part of the cellular defense mechanism with the basic aim of inducing an antiviral state. However, viruses can exploit enhanced cell signalling activities to support various stages of their replication cycles. Kinase activity can be inhibited by small molecule chemical inhibitors, so one strategy to develop antiviral drugs is to target these cellular signalling pathways. In this review, we provide an overview on the current understanding of various cellular and viral events regulated by the p38 signalling pathway, with a special emphasis on targeting these events for antiviral drug development which might identify candidates with broad spectrum activity.
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http://dx.doi.org/10.1002/rmv.2217DOI Listing
January 2021

Isolation and characterization of lumpy skin disease virus from cattle in India.

PLoS One 2021 11;16(1):e0241022. Epub 2021 Jan 11.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India.

Lumpy skin disease (LSD) has devastating economic impact. During the last decade, LSD had spread to climatically new and previously disease-free countries, which also includes its recent emergence in the Indian subcontinent (2019). This study deals with the LSD outbreak(s) from cattle in Ranchi (India). Virus was isolated from the scabs (skin lesions) in the primary goat kidney cells. Phylogenetic analysis based on nucleotide sequencing of LSD virus (LSDV) ORF011, ORF012 and ORF036 suggested that the isolated virus (LSDV/Bos taurus-tc/India/2019/Ranchi) is closely related to Kenyan LSDV strains. Further, we adapted the isolated virus in Vero cells. Infection of the isolated LSDV to Vero cells did not produce cytopathic effect (CPE) until the 4th blind passage, but upon adaptation, it produced high viral titres in the cultured cells. The kinetics of viral DNA synthesis and one-step growth curve analysis suggested that Vero cell-adapted LSDV initiates synthesizing its genome at ~24 hours post-infection (hpi) with a peak level at ~96 hpi whereas evidence of progeny virus particles was observed at 36-48 hours (h) with a peak titre at ~120 h. To the best of our knowledge, this study describes the first successful isolation of LSDV in India, besides providing insights into the life cycle Vero cell-adapted LSDV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241022PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799759PMC
April 2021

FOXP1 negatively regulates intrinsic excitability in D2 striatal projection neurons by promoting inwardly rectifying and leak potassium currents.

Mol Psychiatry 2021 Jun 5;26(6):1761-1774. Epub 2021 Jan 5.

Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Heterozygous loss-of-function mutations in the transcription factor FOXP1 are strongly associated with autism. Dopamine receptor 2 expressing (D2) striatal projection neurons (SPNs) in heterozygous Foxp1 (Foxp1) mice have higher intrinsic excitability. To understand the mechanisms underlying this alteration, we examined SPNs with cell-type specific homozygous Foxp1 deletion to study cell-autonomous regulation by Foxp1. As in Foxp1 mice, D2 SPNs had increased intrinsic excitability with homozygous Foxp1 deletion. This effect involved postnatal mechanisms. The hyperexcitability was mainly due to down-regulation of two classes of potassium currents: inwardly rectifying (K) and leak (K). Single-cell RNA sequencing data from D2 SPNs with Foxp1 deletion indicated the down-regulation of transcripts of candidate ion channels that may underlie these currents: Kcnj2 and Kcnj4 for K and Kcnk2 for K. This Foxp1-dependent regulation was neuron-type specific since these same currents and transcripts were either unchanged, or very little changed, in D1 SPNs with cell-specific Foxp1 deletion. Our data are consistent with a model where FOXP1 negatively regulates the excitability of D2 SPNs through K and K by transcriptionally activating their corresponding transcripts. This, in turn, provides a novel example of how a transcription factor may regulate multiple genes to impact neuronal electrophysiological function that depends on the integration of multiple current types - and do this in a cell-specific fashion. Our findings provide initial clues to altered neuronal function and possible therapeutic strategies not only for FOXP1-associated autism but also for other autism forms associated with transcription factor dysfunction.
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http://dx.doi.org/10.1038/s41380-020-00995-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255328PMC
June 2021

Interaction of metal oxide nanoparticles with microplastics: Impact of weathering under riverine conditions.

Water Res 2021 Feb 9;189:116622. Epub 2020 Nov 9.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, 741246, India; Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, 741246, India. Electronic address:

The ubiquitous distribution of microplastics (MPs) leads to inevitable interactions with the toxic pollutants present in the environment including metal-oxide nanoparticles. This study investigates the interaction of CeO nanoparticles (CeNPs) with MPs generated from a disposable plastic container. Further, rough MPs (R-MPs), generated through mechanical abrasion of MPs with sand, were used to probe the impact of roughness. To understand the sorption kinetics and underlying interaction processes, batch experiments were carried out. The results distinctly indicate that CeNPs sorption occurred on MPs surfaces and was consistent with the pseudo-second order kinetics model. For pristine MPs, the sorption capacity was as high as 12.9 mg/g while for R-MPs kinetic equilibrium was achieved faster and an enhanced sorption capacity (13.4 mg/g) was identified. A rise in sorption with an increase in salinity was noted while pH and humic acid exhibited a negative correlation. The observed interactions were attributed to the aggregation profile and surface charge of CeNPs and MPs. Surprisingly, CeNPs also got loaded onto MPs in non-agitated and undisturbed conditions. The sorption process was influenced by the type of aqueous matrix and the sorption capacity at equilibrium followed the trend: distilled water> synthetic freshwater> river water. FTIR spectra, zeta potential, SEM imaging, and elemental mapping revealed electrostatic interaction as the dominant mechanism. This work contributes towards the knowledge gap on the environmental risk of MPs.
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http://dx.doi.org/10.1016/j.watres.2020.116622DOI Listing
February 2021

Histone Lysine Demethylase JMJD2D/KDM4D and Family Members Mediate Effects of Chronic Social Defeat Stress on Mouse Hippocampal Neurogenesis and Mood Disorders.

Brain Sci 2020 Nov 9;10(11). Epub 2020 Nov 9.

Epigenetics & Neuropsychiatric Disorders Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Habsiguda, Hyderabad, Telangana 500007, India.

Depression, anxiety and related mood disorders are major psychiatric illnesses worldwide, and chronic stress appears to be one of the primary underlying causes. Therapeutics to treat these debilitating disorders without a relapse are limited due to the incomplete molecular understanding of their etiopathology. In addition to the well-studied genetic component, research in the past two decades has implicated diverse epigenetic mechanisms in mediating the negative effects of chronic stressful events on neural circuits. This includes the cognitive circuitry, where the dynamic hippocampal dentate gyrus (DG) neurogenesis gets affected in depression and related affective disorders. Most of these epigenetic studies have focused on the impact of acetylation/deacetylation and methylation of several histone lysine residues on neural gene expression. However, there is a dearth of investigation into the role of demethylation of these lysine residues in chronic stress-induced changes in neurogenesis that results in altered behaviour. Here, using the chronic social defeat stress (CSDS) paradigm to induce depression and anxiety in C57BL/6 mice and DG neural stem/progenitor cell (NSCs/NPCs) culture we show the role of the members of the JMJD2/KDM4 family of histone lysine demethylases (KDMs) in mediating stress-induced changes in DG neurogenesis and mood disorders. The study suggests a critical role of JMJD2D in DG neurogenesis. Altered enrichment of JMJD2D on the promoters of (inhibitor of differentiation 2) and (SRY-Box Transcription Factor 2) was observed during proliferation and differentiation of NSCs/NPCs obtained from the DG. This would affect the demethylation of repressive epigenetic mark H3K9, thus activating or repressing these and possibly other genes involved in regulating proliferation and differentiation of DG NSCs/NPCs. Treatment of the NSCs/NPCs culture with Dimethyloxallyl Glycine (DMOG), an inhibitor of JMJDs, led to attenuation in their proliferation capacity. Additionally, systemic administration of DMOG in mice for 10 days induced depression-like and anxiety-like phenotype without any stress exposure.
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http://dx.doi.org/10.3390/brainsci10110833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695311PMC
November 2020

Metal oxide nanoparticles and polycyclic aromatic hydrocarbons alter nanoplastic's stability and toxicity to zebrafish.

J Hazard Mater 2021 04 27;407:124382. Epub 2020 Oct 27.

Department of Zoology, Goa University, Taleigao Plateau, Goa 403206, India.

Co-occurrence of nanoplastics (NPs) with metal oxide nanoparticles (nMOx) and polycyclic aromatic hydrocarbons (PAHs) have been widely reported. However, there is a scarcity of information on their interactions and combined toxic effects. In this study, we used two different sized NPs [55 nm (NP1) and 100 nm (NP2)] to understand the effect of nMOx (nCuO and nZnO) and PAHs [chrysene (Chr) and fluoranthene (Flu)] on NPs' stability and toxicity to zebrafish. Results revealed that increasing the concentration of nMOx, zeta-potential increased, and charge reversal was observed in NPs suspension while PAH produced no major changes. Aggregation kinetics performed with nMOx exhibited higher aggregation of NPs in presence of NaCl that alleviated critical coagulation concentration. NP1 stabilized the size of otherwise unstable nMOx suspension in the tap-water for a longer period, whereas, aggregation was observed with NP2. The in vivo comet assay results showed that NP1 was more genotoxic than NP2 owing to their lower size. Interestingly the DNA damage was highest in NPs+nMOx followed by nMOx and NPs. Unlike nMOx, Chr/Flu+NPs showed reduced DNA damage as compared to NPs or PAH alone. Alteration in catalase activity and lipid peroxidation value indicated oxidative stress in all exposure groups.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124382DOI Listing
April 2021

Overcoming presynaptic effects of VAMP2 mutations with 4-aminopyridine treatment.

Hum Mutat 2020 11 1;41(11):1999-2011. Epub 2020 Oct 1.

Department of Psychiatry, Weill Institute for Neurosciences and Kavli Institute for Fundamental Neuroscience, School of Medicine, University of California, San Francisco, San Francisco, California, USA.

Clinical and genetic features of five unrelated patients with de novo pathogenic variants in the synaptic vesicle-associated membrane protein 2 (VAMP2) reveal common features of global developmental delay, autistic tendencies, behavioral disturbances, and a higher propensity to develop epilepsy. For one patient, a cognitively impaired adolescent with a de novo stop-gain VAMP2 mutation, we tested a potential treatment strategy, enhancing neurotransmission by prolonging action potentials with the aminopyridine family of potassium channel blockers, 4-aminopyridine and 3,4-diaminopyridine, in vitro and in vivo. Synaptic vesicle recycling and neurotransmission were assayed in neurons expressing three VAMP2 variants by live-cell imaging and electrophysiology. In cellular models, two variants decrease both the rate of exocytosis and the number of synaptic vesicles released from the recycling pool, compared with wild-type. Aminopyridine treatment increases the rate and extent of exocytosis and total synaptic charge transfer and desynchronizes GABA release. The clinical response of the patient to 2 years of off-label aminopyridine treatment includes improved emotional and behavioral regulation by parental report, and objective improvement in standardized cognitive measures. Aminopyridine treatment may extend to patients with pathogenic variants in VAMP2 and other genes influencing presynaptic function or GABAergic tone, and tested in vitro before treatment.
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http://dx.doi.org/10.1002/humu.24109DOI Listing
November 2020

Antiviral activity of Apigenin against buffalopox: Novel mechanistic insights and drug-resistance considerations.

Antiviral Res 2020 09 21;181:104870. Epub 2020 Jul 21.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India. Electronic address:

We describe herein that Apigenin, which is a dietary flavonoid, exerts a strong in vitro and in ovo antiviral efficacy against buffalopox virus (BPXV). Apigenin treatment was shown to inhibit synthesis of viral DNA, mRNA and proteins, without affecting other steps of viral life cycle such as attachment, entry and budding. Although the major mode of antiviral action of Apigenin was shown to be mediated via targeting certain cellular factors, a modest inhibitory effect of Apigenin was also observed directly on viral polymerase. We also evaluated the selection of drug-resistant virus variants under long-term selection pressure of Apigenin. Wherein Apigenin-resistant mutants were not observed up to ~ P20 (passage 20), a significant resistance was observed to the antiviral action of Apigenin at ~ P30. However, a high degree resistance could not be observed even up to P60. To the best of our knowledge, this is the first report describing in vitro and in ovo antiviral efficacy of Apigenin against poxvirus infection. The study also provides mechanistic insights on the antiviral activity of Apigenin and selection of potential Apigenin-resistant mutants upon long-term culture.
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http://dx.doi.org/10.1016/j.antiviral.2020.104870DOI Listing
September 2020

Impact of long-term storage of various redox-sensitive supported nanocomposites on their application in removal of dyes from wastewater: Mechanisms delineation through spectroscopic investigations.

J Hazard Mater 2021 01 2;401:123375. Epub 2020 Jul 2.

Environmental Nanoscience Laboratory, Department of Earth Sciences & Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, 741246, India. Electronic address:

For the prevention of freshwater reservoirs from contamination through industrial effluents, eco-friendly adsorbents with minimal aging impact are required. Here, redox-sensitive nanoscale zero-valent iron(nZVI) particles were supported on four different surfaces with varying bentonite(B)/charcoal(C) ratio to mimic layered and porous surfaces. Different dyes, i.e. rhodamine-B(RB) and methylene blue(MB) were reacted with redox-sensitive supported nZVI composites, and degradation mechanisms were delineated using FT-IR spectroscopic analysis of reaction precipitates. A 300-day exposure to open-air was provided to the composites to comparatively evaluate the impact of aging on their reactivity for dyes in wastewater. Results interpret that dyes removal was a combination of different interfacial chemical processes, i.e., reduction or organic degradation probably through Fenton like processes, along with sorption. These mechanisms were found to be surface dependent, i.e., nZVI on charcoal enriched porous surfaces, degrade dyes through organic degradation while on layered clay surfaces, MB gets removed through reduction with limited and slower RB removal. Nanocomposites show a minimal impact of aging with removal capacities >100 mg/g for BC-1/3-nZVI and C-nZVI for MB and 50-75 mg/g for RB with significant removal in wastewater. Overall, the study concludes C-nZVI and novel BC-1/3-nZVI as two efficient dye adsorbents with minimal aging impact.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123375DOI Listing
January 2021

Application of Zn/Al layered double hydroxides for the removal of nano-scale plastic debris from aqueous systems.

J Hazard Mater 2020 10 15;397:122769. Epub 2020 May 15.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur, 741246, West Bengal, India; Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur, 741246, West Bengal, India. Electronic address:

Nano-scale plastic debris (NPDs) are emerging as potential contaminants as they can be easily ingested by aquatic organisms and carry many pollutants in the environment. This study is aimed to remove NPDs from aqueous environment for the first time by using eco-friendly adsorption techniques. Initially, the interaction between NPDs and synthesized Zn-Al layered double hydroxide (LDH) was confirmed by pH titration of Zn-Al LDH against NPDs at varying mass ratio (50:1 to 50:7) and FTIR analysis for both before and after 2 h of contact time. Fast removal was observed in deionized water and synthetic freshwater with maximum sorption capacity (Q) of 164.49 mg/g,162.62 mg/g, respectively, according to Sips isotherm. Whereas, removal was least in synthetic hard water having a Q value of 53 mg/g. For 2 mM concentration of SO and PO, the adsorption capacity significantly decreased to 2%. The removal efficiency was found 100 % at pH 4, while at pH 9, it reached 37 % due to increased competitive binding and destabilization of LDH under alkaline conditions. The process of sorption was spontaneous in different types of water studied. The study reveals that Zn-Al LDH can be used as potential adsorbent for the removal of NPDs from freshwater systems.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122769DOI Listing
October 2020

Isolation and characterization of bovine herpes virus 5 (BoHV5) from cattle in India.

PLoS One 2020 24;15(4):e0232093. Epub 2020 Apr 24.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India.

Bovine herpesvirus 1 (BoHV1) and 5 (BoHV5) are genetically and antigenically related alphaherpesviruses. Infection with one virus induces protective immunity against the other. However, disease associated with BoHV1 and BoHV5 varies significantly; whereas BoHV1 infection is usually associated with rhinotracheitis and abortion, BoHV5 causes encephalitis in cattle. BoHV5 outbreaks are sporadic and mainly restricted to the South American countries. We report BoHV5 infection for the first time from aborted cattle in India. Based on the characteristic cytopathic effects in MDBK cells, amplification of the viral genome by PCR, differential PCR for BoHV1/BoHV5, nucleotide sequencing and restriction endonuclease patterns, identity of the virus was confirmed as BoHV5 subtype A. Serum samples from the aborted cattle strongly neutralized both BoHV1 and BoHV5 suggesting an active viral infection in the herd. Upon UL27, UL44 and UL54 gene-based sequence and phylogenetic analysis, the isolated virus clustered with BoHV5 strains and showed highest similarity with the Brazilian BoHV5 strains.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232093PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182196PMC
July 2020

Effect of the irrigation water type and other environmental parameters on CeO nanopesticide-clay colloid interactions.

Environ Sci Process Impacts 2020 Jan 18;22(1):84-94. Epub 2019 Dec 18.

Environmental Nanoscience Laboratory, Department of Earth Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India - 741246. and Centre for Climate and Environmental Studies, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal 741246, India.

In this work, the stability and aggregation behaviour of CeO nanoparticles (NPs) was investigated to predict their fate in the agricultural environment. For this, the aggregation kinetics of CeO NPs was studied under varying pH, ionic strength (IS), dissolved organic matter (DOM) and carbonate concentrations in the presence of clay. Furthermore, different types of irrigation water have been used to check the fate of CeO nanoparticles (NPs) in complex aqueous matrices. The results show that critical coagulation concentration (CCC) values obtained for CeO NPs, i.e. 26.5 mM and 7.9 mM for NaCl and CaCl respectively, drastically decreased to 16.2 mM and 1.87 mM in the presence of bentonite clay colloids, which may lead to their deposition within the soil matrix. However, the presence of bicarbonate ions (0.1-2 mM) along with DOM (1-20 mg L) may result in their stabilization and co-transport of CeO NPs with clay in water bodies having low ionic strength. It was also observed that the negative charge of a bentonite clay suspension was completely reversed with an increase in CeO concentration by 37.5 times. The critical charge reversal concentration value was 284.4 mg L in Milli-Q water whereas values were observed to be 680 mg L in synthetic-soft water, followed by natural river water (867 mg L) and synthetic-hard water (910 mg L). The synergistic effect of temperature and ionic strength was observed on the aggregation behaviour of CeO NPs in environmental water samples of varying composition.
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http://dx.doi.org/10.1039/c9em00428aDOI Listing
January 2020

Polyalthia longifolia leaves methanolic extract targets entry and budding of viruses-an in vitro experimental study against paramyxoviruses.

J Ethnopharmacol 2020 Feb 7;248:112279. Epub 2019 Oct 7.

Department of Pharmacology and Toxicology, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan (DUVASU), Mathura, India. Electronic address:

Ethnopharmacological Relevance: Synthetic antiviral drugs have several limitations including high cost. Thus research on antiviral property of medicinal plants is continuously gaining importance. Polyalthia longifolia possesses several medicinal properties and has been used in traditional ayurvedic medicine for treatment of dermatological ailments as kushta, visarpa/herpes virus infection and also to treat pyrexia of unknown origin as mentioned in Visarpa Chikitsa.

Aim Of The Study: Keeping in view the cytotoxic, anti-cancer activity and antiviral efficacy of Polyalthia longifolia against herpes, present study was undertaken to evaluate the in vitro antiviral activity of methanolic extract of Polyalthia longifolia leaves, if any, and to unravel the possible target(s)/mechanism of action.

Material And Methods: Antiviral activity of Polyalthia longifolia methanolic extract was studied using Vero cell lines against paramyxoviruses, namely-peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV). Cytotoxicity of the test extract was evaluated employing MTT assay. Virucidal activity, and viral-attachment, virus entry and release assays were determined in Vero cells using standard experimental protocols. The viral RNA in the virus-infected cells was quantified by qRT-PCR.

Results: At non-cytotoxic concentration, methanolic extract of Polyalthia longifolia leaves was found to inhibit the replication of PPRV and NDV at viral entry and budding level, whereas other steps of viral life cycle such as attachment and RNA synthesis remained unaffected.

Conclusions: Polyalthia longifolia leaves extract possesses promising antiviral activity against paramyxoviruses and acts by inhibiting the entry and budding of viruses; and this plant extract evidently possesses excellent and promising potential for development of effective herbal antiviral drug.
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http://dx.doi.org/10.1016/j.jep.2019.112279DOI Listing
February 2020

miR-30 Family miRNAs Mediate the Effect of Chronic Social Defeat Stress on Hippocampal Neurogenesis in Mouse Depression Model.

Front Mol Neurosci 2019 8;12:188. Epub 2019 Aug 8.

Epigenetics and Neuropsychiatric Disorders' Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India.

Depression is a debilitating psychiatric disorder with a high rate of relapse and a low rate of response to antidepressant treatment. There is a dearth of new antidepressants due to an incomplete understanding of the molecular mechanisms involved in its etiopathology. Chronic stress appears to be one of the foremost underlying causes of depression. Studies in animal models in the past decade have implicated epigenetic mechanisms in mediating the negative effects of chronic stressful events on the progression/manifestation of depression and other co-morbid neuropsychiatric disorders. However, non-coding RNAs, another layer of epigenetic regulation is relatively less studied in depression. Here, using the chronic social defeat stress (CSDS)-induced depression model, we hypothesized dysregulation in miRNA-mRNA networks in the neurogenic dentate gyrus (DG) region of male C57BL/6 mice. Among several dysregulated miRNAs identified miRNA arrays, the most striking finding was the downregulation of miRNAs of the miR-30 family in stressed/defeated mice. To investigate miRNAs in the DG-resident neural stem/progenitor cells (NSCs/NPCs), we used the neurosphere culture, where proliferating NSCs/NPCs were subjected to differentiation. Among several differentially expressed miRNAs, we observed an upregulation of miR-30 family miRNAs upon differentiation. To search for the gene targets of these miRNAs, we performed gene arrays followed by bioinformatics analysis, miRNA manipulations and luciferase assays. Our results suggest that miR-30 family miRNAs mediate chronic stress-induced depression-like phenotype by altering hippocampal neurogenesis and neuroplasticity controlling the epigenetic and transcription regulators such as and ; and cell signaling regulators like , and .
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http://dx.doi.org/10.3389/fnmol.2019.00188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694739PMC
August 2019

Disrupting the hippocampal Piwi pathway enhances contextual fear memory in mice.

Neurobiol Learn Mem 2019 05 6;161:202-209. Epub 2019 Apr 6.

Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

The Piwi pathway is a conserved gene regulatory mechanism comprised of Piwi-like proteins and Piwi-interacting RNAs, which modulates gene expression via RNA interference and through interaction with epigenetic mechanisms. The mammalian Piwi pathway has been defined by its role in transposon control during spermatogenesis; however, despite an increasing number of studies demonstrating its expression in the nervous system, relatively little is known about its function in neurons or potential contribution to behavioural regulation. We have discovered that all three Piwi-like genes are expressed in the adult mouse brain, and that viral-mediated knockdown of the Piwi-like genes Piwil1 and Piwil2 in the dorsal hippocampus leads to enhanced contextual fear memory without affecting generalised anxiety. These results implicate the Piwi pathway in behavioural regulation in the adult mammalian brain, likely through modulation of plasticity-related gene expression.
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http://dx.doi.org/10.1016/j.nlm.2019.04.002DOI Listing
May 2019

Inhibitor of Sarco/Endoplasmic Reticulum Calcium-ATPase Impairs Multiple Steps of Paramyxovirus Replication.

Front Microbiol 2019 13;10:209. Epub 2019 Feb 13.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India.

Sarco/endoplasmic reticulum calcium-ATPase (SERCA) is a membrane-bound cytosolic enzyme which is known to regulate the uptake of calcium into the sarco/endoplasmic reticulum. Herein, we demonstrate for the first time that SERCA can also regulate virus replication. Treatment of Vero cells with SERCA-specific inhibitor (Thapsigargin) at a concentration that is nontoxic to the cells significantly reduced Peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV) replication. Conversely, overexpression of SERCA rescued the inhibitory effect of Thapsigargin on virus replication. PPRV and NDV infection induced SERCA expression in Vero cells, which could be blocked by Thapsigargin. Besides inducing enhanced formation of cytoplasmic foci, Thapsigargin was shown to block viral entry into the target cells as well as synthesis of viral proteins. Furthermore, NDV was shown to acquire significant resistance to Thapsigargin upon long-term passage (P) in Vero cells. As compared to the P0 and P70-Control, the fusion (F) protein of P70-Thapsigargin virus exhibited a unique mutation at amino acid residue 104 (E104K), whereas no Thapsigargin-associated mutations were observed in HN gene. To the best of our knowledge, this is the first report describing the virus-supportive role of SERCA and a rare report suggesting that viruses may acquire resistance even in the presence of an inhibitor that targets a cellular factor.
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http://dx.doi.org/10.3389/fmicb.2019.00209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381065PMC
February 2019

Increased stress and altered expression of histone modifying enzymes in brain are associated with aberrant behaviour in vitamin B12 deficient female mice.

Nutr Neurosci 2020 Sep 25;23(9):714-723. Epub 2018 Nov 25.

National Institute of Nutrition, ICMR, Hyderabad 500007, India.

A sub-optimal nutritional environment from early life can be envisaged as a stressor that translates into mental health problems in adulthood. After considering (a) the widespread prevalence of vitamin B12 deficiency especially amongst women in developing countries and (b) the importance of vitamin B12 in normal brain function, in this study we have elucidated the behavioural correlates of chronic severe and moderate vitamin B12 deficiency in C57BL/6 mice. Female weanling mice were assigned to three dietary groups: (a) control AIN-76A diet with cellulose as dietary fibre (b) vitamin B12 restricted AIN-76A diet with pectin as dietary fibre (severe deficiency group) and (c) vitamin B12 restricted AIN-76A diet with cellulose as dietary fibre (moderate deficiency group). The mice received these diets throughout pregnancy, lactation and thereafter. Nest-building, maternal care, anxiety and depressive behaviours were evaluated. Oxidative stress, activities of antioxidant enzymes and expression of various histone modifying enzymes in brain were investigated to unravel the probable underlying mechanisms. Our data suggests that both severe and moderate vitamin B12 deficiency induced anxiety and impaired maternal care. However, only severe vitamin B12 deficiency induced depression. Oxidative stress and poor antioxidant defense underlie the deleterious effects of both severe and moderate vitamin B12 deficiency. Altered expression of histone modifying enzymes in the brain of severely deficient mice is suggestive of epigenetic reprogramming. This study suggests that chronic vitamin B12 deficiency leads to behavioural anomalies in female C57BL/6 mice and the severity of these outcomes can be correlated to the level of deficiency.
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http://dx.doi.org/10.1080/1028415X.2018.1548676DOI Listing
September 2020

MNK1 inhibitor as an antiviral agent suppresses buffalopox virus protein synthesis.

Antiviral Res 2018 12 28;160:126-136. Epub 2018 Oct 28.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India. Electronic address:

A small molecule chemical inhibitor CGP57380 that blocks activation of MAPK interacting kinase 1 (MNK1) was found to significantly suppress buffalopox virus (BPXV) replication. BPXV infection was shown to induce MNK1 activation. Depletion of MNK1 by small interfering RNA (siRNA), blocking activation of extracellular regulated kinase (ERK, an upstream activator of MNK1) and disruption of eIF4E/eIF4G interaction (downstream substrate of MNK1 which plays a central role in cap-dependent translation initiation), resulted in reduced BPXV replication, suggesting that ERK/MNK1/eIF4E signaling is a prerequisite for BPXV replication. With the help of time-of-addition and virus step-specific assays, CGP57380 treatment was shown to decrease synthesis of viral genome (DNA). Disruption of ERK/MNK1/eIF4E signaling resulted in reduced synthesis of viral proteins, suggesting that BPXV utilizes cap-dependent mechanism of translation initiation. Therefore, we concluded that decreased synthesis of viral genome in presence of MNK1 inhibitor is the result of reduced synthesis of viral proteins. Furthermore, BPXV was sequentially passaged (P = 40) in presence of CGP57380 or vehicle control (DMSO). As compared to P0 and P40-control viruses, P40-CGP57380 virus replicated at significantly higher (∼10-fold) titers in presence of CGP57380, although a complete resistance could not be achieved. In a BPXV egg infection model, CGP57380 was found to prevent development of pock lesions on chorioallantoic membrane (CAM) as well as associated mortality of the embryonated chicken eggs. We for the first time demonstrated in vitro and in ovo antiviral efficacy of CGP57380 against BPXV and identified that ERK/MNK1 signaling is a prerequisite for synthesis of viral proteins. Our study also describes a rare report about generation of drug-resistant viral variants against a host-targeting antiviral agent.
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http://dx.doi.org/10.1016/j.antiviral.2018.10.022DOI Listing
December 2018

Role of MAPK/MNK1 signaling in virus replication.

Virus Res 2018 07 1;253:48-61. Epub 2018 Jun 1.

Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, Haryana 125001, India. Electronic address:

Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication. Some of the host factors might be dispensable for the host but may be critical for virus replication; therefore such cellular factors may serve as targets for development of antiviral therapeutics. Mitogen activated protein kinase (MAPK) is a major cell signaling pathway that is known to be activated by diverse group of viruses. MAPK interacting kinase 1 (MNK1) has been shown to regulate both cap-dependent and internal ribosomal entry sites (IRES)-mediated mRNA translation. In this review we have discuss the role of MAPK in virus replication, particularly the role of MNK1 in replication and translation of viral genome.
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http://dx.doi.org/10.1016/j.virusres.2018.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114592PMC
July 2018

A Functional Role for the Epigenetic Regulator ING1 in Activity-induced Gene Expression in Primary Cortical Neurons.

Neuroscience 2018 01 20;369:248-260. Epub 2017 Nov 20.

Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Epigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin, Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) of Ppp3r1 depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair.
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http://dx.doi.org/10.1016/j.neuroscience.2017.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766419PMC
January 2018

Leucine-rich repeat-containing 8B protein is associated with the endoplasmic reticulum Ca leak in HEK293 cells.

J Cell Sci 2017 Nov 2;130(22):3818-3828. Epub 2017 Oct 2.

Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India

Leucine-rich repeat-containing 8 (LRRC8) proteins have been proposed to evolutionarily originate from the combination of the channel protein pannexin, and a leucine-rich repeat (LRR) domain. Five paralogs of LRRC8, namely LRRC8A, LRRC8B, LRRC8C, LRRC8D and LRRC8E have been reported. LRRC8A has been shown to be instrumental in cell swelling. Here, we identify LRRC8B as a key player in the cellular Ca signaling network. Overexpression of human LRRC8B in HEK293 cells reduced the Ca level in the endoplasmic reticulum (ER). LRRC8B-overexpressing cells exhibited a lesser release of Ca from the ER in response to ATP, carbachol and intracellular administration of inositol (1,4,5)-trisphosphate (IP). LRRC8B-knockdown cells showed a slower depletion of the ER Ca stores when sarco-endoplasmic reticulum Ca-ATPase was blocked with thapsigargin (TG), while overexpression of LRRC8B had the opposite effect. LRRC8B-overexpressing cells exhibited a higher level of store-operated Ca entry following store-depletion by TG. Collectively, LRRC8B participates in intracellular Ca homeostasis by acting as a leak channel in the ER. This study gives a fundamental understanding of the role of a novel protein in the elemental cellular process of ER Ca leak and expands the known roles for LRRC8 proteins.This article has an associated First Person interview with the first author of the paper.
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http://dx.doi.org/10.1242/jcs.203646DOI Listing
November 2017
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