Publications by authors named "K Aparna Sharma"

3,373 Publications

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Simultaneous detection of aqueous aluminum(III) and chromium(III) using reduced and capped silver nanoparticles.

Int J Phytoremediation 2021 Sep 24:1-14. Epub 2021 Sep 24.

School of Chemical Sciences, Central University of Gujarat, Gandhinagar, India.

There is a significant interest to develop sensing devices that detect water toxins, especially heavy metal ions. Although there have already been numerical reports on detecting toxic heavy metal ions, the use of adaptable devices could enable a broader range of sensing applications. Here, we used fresh peel extract (PeA) and dried peel extract (DPeA) of (Avocado) as a reducing and capping agent to synthesize and stabilize AgNPs. The dimensions of NPs were controlled by tuning pH, temperature, and volume of the reducing agent. The sensitivity and selectivity of the AgNPs toward various metal ions viz. Ni(II), Cd(II), Al(III), Hg(II), Cr(III), Ba(II), Pb(II), Zn(II), Co(II), Mn(II), Cu(II), Ca(II), Mg(II), and K(I) were studied. The detection probe was found to be selective and sensitive toward Al(III) and Cr(III) ions with the detection limit of 0.04 ppm and 0.05 ppm, respectively. High-resolution transmission electron microscope (HRTEM), ultraviolet-visible (UV-Vis) spectroscopy, and dynamic light scattering (DLS) analysis results confirm an agglomeration-based mechanism for sensing both metal ions. This method can be exploited for the colorimetric detection of toxic heavy metals in real water samples.
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http://dx.doi.org/10.1080/15226514.2021.1977911DOI Listing
September 2021

Endothelial Stromal PD-L1 (Programmed Death Ligand 1) Modulates CD8 T-Cell Infiltration After Heart Transplantation.

Circ Heart Fail 2021 Sep 24:CIRCHEARTFAILURE120007982. Epub 2021 Sep 24.

Department of Pathology, School of Medicine (W.B.-B., T.W., M.V.T., R.A.A., Q.Z., M.K.H., D.Č.).

Background: The role of checkpoint axes in transplantation has been partially addressed in animal models but not in humans. Occurrence of fulminant myocarditis with allorejection-like immunologic features in patients under anti-PD1 (programmed death cell protein 1) treatment suggests a key role of the PD1/PD-L1 (programmed death ligand 1) axis in cardiac immune homeostasis.

Methods: We cross-sectionally studied 23 heart transplant patients undergoing surveillance endomyocardial biopsy. Endomyocardial tissue and peripheral blood mononuclear cells were analyzed by flow cytometry. Multivariate logistic regression analyses including demographic, clinical, and hemodynamic parameters were performed. Murine models were used to evaluate the impact of PD-L1 endothelial graft expression in allorejection.

Results: We found that myeloid cells dominate the composition of the graft leukocyte compartment in most patients, with variable T-cell frequencies. The CD (cluster of differentiation) 4:CD8 T-cell ratios were between 0 and 1.5. The proportion of PD-L1 expressing cells in graft endothelial cells, fibroblasts, and myeloid leukocytes ranged from negligible up to 60%. We found a significant inverse logarithmic correlation between the proportion of PD-L1HLA (human leukocyte antigen)-DR endothelial cells and CD8 T cells (slope, -18.3 [95% CI, -35.3 to -1.3]; =0.030). PD-L1 expression and leukocyte patterns were independent of demographic, clinical, and hemodynamic parameters. We confirmed the importance of endothelial PD-L1 expression in a murine allogeneic heart transplantation model, in which grafts lacking PD-L1 in endothelial cells were rejected significantly faster than controls.

Conclusions: Loss of graft endothelial PD-L1 expression may play a role in regulating CD8 T-cell infiltration in human heart transplantation. Murine model results suggest that loss of graft endothelial PD-L1 may facilitate alloresponses and rejection.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007982DOI Listing
September 2021

Discovery and evaluation of entry inhibitors for SARS-CoV-2 and its emerging variants.

J Virol 2021 Sep 22:JVI0143721. Epub 2021 Sep 22.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68131, USA.

The outbreak of SARS-CoV-2 is responsible for the COVID-19 pandemic. Despite unprecedented research and developmental efforts, SARS-CoV-2-specific antivirals are still unavailable for the treatment of COVID-19. In most instances, SARS-CoV-2 infection initiates with the binding of spike glycoprotein to the host cell ACE2 receptor. Utilizing the crystal structure of the ACE2/Spike receptor-binding domain (S-RBD) complex (PDB file 6M0J) in a computer-aided drug design (CADD) approach, we identified and validated 5 potential inhibitors of S-RBD and ACE-2 interaction. Two of the five compounds, MU-UNMC-1 and MU-UNMC-2, blocked the entry of pseudovirus particles expressing SARS-CoV-2 Spike glycoprotein. In live SARS-CoV-2 infection assays, both the compounds showed antiviral activity with IC values in the micromolar range (MU-UNMC-1: IC= 0.67 μM and MU-UNMC-2: IC= 1.72 μM) in human bronchial epithelial cells. Furthermore, MU-UNMC-1 and MU-UNMC-2 effectively blocked the replication of rapidly transmitting variants of concern: South African variant B.1.351 (IC= 9.27 μM & 3.00 μM) and Scotland variant B.1.222 (IC= 2.64 μM & 1.39 μM) respectively. Following these assays, we conducted 'induced-fit (flexible) docking' to understand the binding mode of MU-UNMC-1/MU-UNMC-2 at the S-RBD/ACE2 interface. Our data showed that mutation N501Y (present in B.1.351 variant) alters the binding mode of MU-UNMC-2 such that it is partially exposed to the solvent and has reduced polar contacts. Finally, MU-UNMC-2 displayed high synergy with remdesivir (RDV), the only approved drug for treating hospitalized COVID-19 patients. The ongoing coronavirus infectious disease 2019 (COVID-19) pandemic is caused by a novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More than 207 million people have been infected globally, and 4.3 million have died due to this viral outbreak. While a few vaccines have been deployed, a SARS-CoV-2 specific antiviral for the treatment of COVID-19 is yet to be approved. As the interaction of SARS-CoV-2 spike protein with ACE2 is critical for cellular entry, using a combination of a computer-aided drug design (CADD) approach and cell-based assays, we report the identification of five potential SARS-CoV-2 entry inhibitors. Out of the five, two compounds (MU-UNMC-1 and MU-UNMC-2) have antiviral activity against ancestral SARS-CoV-2 and emerging variants from South Africa and Scotland. Furthermore, MU-UNMC-2 acts synergistically with remdesivir, suggesting that RDV and MU-UNMC-2 can be developed as a combination therapy to treat COVID-19, infected individuals.
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http://dx.doi.org/10.1128/JVI.01437-21DOI Listing
September 2021

Predicting Solvent-Dependent Nucleophilicity Parameter with a Causal Structure Property Relationship.

J Chem Inf Model 2021 Sep 22. Epub 2021 Sep 22.

Institute of Process Research & Development, School of Chemistry, University of Leeds, Leeds, LS2 9JT, United Kingdom.

Solvent-dependent reactivity is a key aspect of synthetic science, which controls reaction selectivity. The contemporary focus on new, sustainable solvents highlights a need for reactivity predictions in different solvents. Herein, we report the excellent machine learning prediction of the nucleophilicity parameter in the four most-common solvents for nucleophiles in the Mayr's reactivity parameter database ( = 0.93 and 81.6% of predictions within ±2.0 of the experimental values with Extra Trees algorithm). A Causal Structure Property Relationship (CSPR) approach was utilized, with focus on the physicochemical relationships between the descriptors and the predicted parameters, and on rational improvements of the prediction models. The nucleophiles were represented with a series of electronic and steric descriptors and the solvents were represented with principal component analysis (PCA) descriptors based on the ACS Solvent Tool. The models indicated that steric factors do not contribute significantly, because of bias in the experimental database. The most important descriptors are solvent-dependent HOMO energy and Hirshfeld charge of the nucleophilic atom. Replacing DFT descriptors with Parameterization Method 6 (PM6) descriptors for the nucleophiles led to an 8.7-fold decrease in computational time, and an ∼10% decrease in the percentage of predictions within ±2.0 and ±1.0 of the experimental values.
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http://dx.doi.org/10.1021/acs.jcim.1c00610DOI Listing
September 2021

Proteomic landscape of Japanese encephalitis virus-infected fibroblasts.

J Gen Virol 2021 Sep;102(9)

Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India.

Advances in proteomics have enabled a comprehensive understanding of host-pathogen interactions. Here we have characterized Japanese encephalitis virus (JEV) infection-driven changes in the mouse embryonic fibroblast (MEF) proteome. Through tandem mass tagging (TMT)-based mass spectrometry, we describe changes in 7.85 % of the identified proteome due to JEV infection. Pathway enrichment analysis showed that proteins involved in innate immune sensing, interferon responses and inflammation were the major upregulated group, along with the immunoproteasome and poly ADP-ribosylation proteins. Functional validation of several upregulated anti-viral innate immune proteins, including an active cGAS-STING axis, was performed. Through siRNA depletion, we describe a crucial role of the DNA sensor cGAS in restricting JEV replication. Further, many interferon-stimulated genes (ISGs) were observed to be induced in infected cells. We also observed activation of TLR2 and inhibition of TLR2 signalling using TLR1/2 inhibitor CU-CPT22-blocked production of inflammatory cytokines IL6 and TNF-α from virus-infected N9 microglial cells. The major proteins that were downregulated by infection were involved in cell adhesion (collagens), transport (solute carrier and ATP-binding cassette transporters), sterol and lipid biosynthesis. Several collagens were found to be transcriptionally downregulated in infected MEFs and mouse brain. Collectively, our data provide a bird's-eye view into how fibroblast protein composition is rewired following JEV infection.
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http://dx.doi.org/10.1099/jgv.0.001657DOI Listing
September 2021
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