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Cerium oxide nanoparticles (CeO2 NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant “glutathione (GSH)” level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L- cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use.

Significance Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is a leading blood-stage malaria vaccine candidate that elicits potent strain-transcending invasion inhibitory antibodies. However, it lacks both transmembrane domains and a GPI-anchor and is thus anchored to the merozoite surface through an unknown mechanism. We have demonstrated that PfRH5 and its known partner, PfRH5-interacting protein (PfRipr), associates with a conserved GPI-anchored protein, Cysteine-rich protective antigen (CyRPA), to form a complex on the merozoite surface. CyRPA was shown to be GPI-linked, refractory to knockout, and like PfRH5, elicited potent strain-transcending invasion inhibitory antibodies. This discovery elucidates the formation of a previously unidentified PfRH5/PfRipr/CyRPA protein complex on the merozoite surface, which facilitates the PfRH5–Basigin interaction and offers another highly conserved, potent target (CyRPA) for novel antimalarial strategies that could abrogate formation of this crucial complex. Erythrocyte invasion by Plasmodium falciparum merozoites is a highly intricate process in which Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is an indispensable parasite ligand that binds with its erythrocyte receptor, Basigin. PfRH5 is a leading blood-stage vaccine candidate because it exhibits limited polymorphisms and elicits potent strain-transcending parasite neutralizing antibodies. However, the mechanism by which it is anchored to the merozoite surface remains unknown because both PfRH5 and the PfRH5-interacting protein (PfRipr) lack transmembrane domains and GPI anchors. Here we have identified a conserved GPI-linked parasite protein, Cysteine-rich protective antigen (CyRPA) as an interacting partner of PfRH5-PfRipr that tethers the PfRH5/PfRipr/CyRPA multiprotein complex on the merozoite surface. CyRPA was demonstrated to be GPI-linked, localized in the micronemes, and essential for erythrocyte invasion. Specific antibodies against the three proteins successfully detected the intact complex in the parasite and coimmunoprecipitated the three interacting partners. Importantly, full-length CyRPA antibodies displayed potent strain-transcending invasion inhibition, as observed for PfRH5. CyRPA does not bind with erythrocytes, suggesting that its parasite neutralizing antibodies likely block its critical interaction with PfRH5-PfRipr, leading to a blockade of erythrocyte invasion. Further, CyRPA and PfRH5 antibody combinations produced synergistic invasion inhibition, suggesting that simultaneous blockade of the PfRH5–Basigin and PfRH5/PfRipr/CyRPA interactions produced an enhanced inhibitory effect. Our discovery of the critical interactions between PfRH5, PfRipr, and the GPI-anchored CyRPA clearly defines the components of the essential PfRH5 adhesion complex for P. falciparum erythrocyte invasion and offers it as a previously unidentified potent target for antimalarial strategies that could abrogate formation of the crucial multiprotein complex.

Plant growth-promoting bacteria (PGPB) enhance plant growth, as well as protect plants from several biotic and abiotic stresses through a variety of mechanisms. Therefore, the exploitation of PGPB in agriculture is feasible as it offers sustainable and eco-friendly approaches to maintaining soil health while increasing crop productivity. The vital key of PGPB application in agriculture is its effectiveness in colonizing plant roots and the phyllosphere, and in developing a protective umbrella through the formation of microcolonies and biofilms. Biofilms offer several benefits to PGPB, such as enhancing resistance to adverse environmental conditions, protecting against pathogens, improving the acquisition of nutrients released in the plant environment, and facilitating beneficial bacteria–plant interactions. Therefore, bacterial biofilms can successfully compete with other microorganisms found on plant surfaces. In addition, plant-associated PGPB biofilms are capable of protecting colonization sites, cycling nutrients, enhancing pathogen defenses, and increasing tolerance to abiotic stresses, thereby increasing agricultural productivity and crop yields. This review highlights the role of biofilms in bacterial colonization of plant surfaces and the strategies used by biofilm-forming PGPB. Moreover, the factors influencing PGPB biofilm formation at plant root and shoot interfaces are critically discussed. This will pave the role of PGPB biofilms in developing bacterial formulations and addressing the challenges related to their efficacy and competence in agriculture for sustainability.

The use of metal oxide nanoparticles (titanium dioxide) in consumer and industrial products improves their quality but also underscores the possible adverse effects to human and environmental health. Mice were exposed orally for 14 consecutive days and analyzed for alteration in different hepatic enzymes, histopathological changes, oxidative stress, DNA damage, tumor suppressor and proapoptotic protein expression in liver cells. We observed a significant alteration in the level of hepatic enzymes and liver histopathology at a dose of 100 mg/kg body weight. Significant oxidative DNA damage was observed in liver cells, which could be attributed to oxidative stress. In addition, the increased expression of p53, BAX, caspase-3 and -9 proteins and decreased expression of antiapoptotic protein Bcl-2, suggest activation of the intrinsic pathway of apoptosis. High accumulation of titanium dioxide nanoparticles in the liver tissue would cause DNA damage and apoptosis through the intrinsic pathway. Original submitted 7 December 2012; Revised submitted 25 April 2013

Erythrocyte invasion by Plasmodium merozoites is a complex, multistep process that is mediated by a number of parasite ligand-erythrocyte receptor interactions. One such family of parasite ligands includes the P. falciparum reticulocyte binding homologue (PfRH) proteins that are homologous with the P. vivax reticulocyte binding proteins and have been shown to play a role in erythrocyte invasion. There are five functional PfRH proteins of which only PfRH2a/2b have not yet been demonstrated to bind erythrocytes. In this study, we demonstrated that native PfRH2a/2b is processed near the N-terminus yielding fragments of 220 kDa and 80 kDa that exhibit differential erythrocyte binding specificities. The erythrocyte binding specificity of the 220 kDa processed fragment of native PfRH2a/2b was sialic acid-independent, trypsin resistant and chymotrypsin sensitive. This specific binding phenotype is consistent with previous studies that disrupted the PfRH2a/2b genes and demonstrated that PfRH2b is involved in a sialic acid independent, trypsin resistant, chymotrypsin sensitive invasion pathway. Interestingly, we found that the smaller 80 kDa PfRH2a/2b fragment is processed from the larger 220 kDa fragment and binds erythrocytes in a sialic acid dependent, trypsin resistant and chymotrypsin sensitive manner. Thus, the two processed fragments of PfRH2a/2b differed with respect to their dependence on sialic acids for erythrocyte binding. Further, we mapped the erythrocyte binding domain of PfRH2a/2b to a conserved 40 kDa N-terminal region (rPfRH2(40)) in the ectodomain that is common to both PfRH2a and PfRH2b. We demonstrated that recombinant rPfRH2(40) bound human erythrocytes with the same specificity as the native 220 kDa processed protein. Moreover, antibodies generated against rPfRH2(40) blocked erythrocyte invasion by P. falciparum through a sialic acid independent pathway. PfRH2a/2b thus plays a key role in erythrocyte invasion and its conserved receptor-binding domain deserves attention as a promising candidate for inclusion in a blood-stage malaria vaccine.

Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes. A total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ) media. Phenotypic drug susceptibility testing (DST) was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method. Of 510 specimens cultured, the total culture positivity obtained was 11.8% (60) encompassing 54 (10.6%) Mycobacterium tuberculosis and 6 (1.2%) non-tubercular mycobacteria (NTM). DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB) in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours. The problem of MDR in extra pulmonary tuberculosis (EPTB) cannot be overlooked and due attention on patients should be given. Routine use of Geno Type MTBDRplus assay for the diagnosis of MDR-EPTB can substantially reduce the time between diagnosis and drug therapy. Culture along with Geno Type MTBDRplus assay could be a solution for rapid and accurate diagnosis of MDR-TB in low bacillary non sputum specimens.

We compare tropospheric column nitrogen dioxide (NO2) in the United Kingdom Chemistry and Aerosol (UKCA) model version 11.0 with satellite measurements from NASA's Earth Observing System (EOS) Aura satellite Ozone Monitoring Instrument (OMI) to investigate the seasonality and trends of tropospheric NO2 over south and east Asia (S and E Asia). UKCA is the atmospheric composition component of the UK Earth System Model (UKESM). UKCA was run with nudged meteorology, producing hourly output over S and E Asia for 2005–2015. OMI averaging kernels have been applied to the model hourly data sampled at Aura's local overpass time of 13:45 LT ± 15 min to allow for consistent model–data comparison. Background UKCA and OMI tropospheric column NO2 typically ranges between 0×1015 and 2×1015 molec.cm-2. Diurnal cycles and vertical profiles of the tropospheric NO2 column in UKCA show that the daily minimum tropospheric column NO2 occurs around the satellite overpass time. UKCA captures the seasonality but overestimates NO2 by a factor of ∼ 2.5, especially during winter over eastern China and north India, at times and locations with high aerosol loadings. Heterogeneous chemistry is represented in the version of UKCA used here as uptake of N2O5 on internally generated sulfate aerosol. However, aerosol surface area may be underestimated in polluted locations, contributing to overestimation of NO2. In addition, the model may underestimate emissions of volatile organic compounds (VOCs) and associated peroxy acetyl nitrate (PAN) formation, leading to insufficient long-range transport of oxidised nitrogen and also contributing to overestimation of NO2 over polluted regions and underestimation over remote regions. Quantifying and understanding discrepancies in modelled NO2 warrant further investigation as they propagate into modelling of multiple environmental issues.

This paper aims to provide a bibliometric review on the diverse decision approaches in uncertain contexts for clean energy system (CES) assessment. A total of 126 publications are analyzed. Previous reviews on CES have discussed several research questions on the decision methods and the applicability of evaluating CES, along with the factors associated with CESs. In the present study, we focus on the bibliometric aspect that attempts to address questions related to the prominence of authors, countries/regions that focus on the current theme, impact of journals, importance of articles in the research community, and so on. The window considered for the study is from 2018 to 2021, with the motive to extend the review process from the preceding works. A review model is presented to address the questions based on the literature evidence. The results infer that CESs are the most viable mode for sustainable development, and the use of decision approaches is apt for the assessment of CESs.

The immense applications of titanium dioxide nanoparticles (TiO2 NPs) in consumer products have raised concerns about their health effects especially because TiO2 NPs can interact with various biomolecules. Out of these, proteins are more prone to alterations owing to their dynamic nature. Different protein conformers co-exist in cellular systems, and studying the interaction of protein conformers with nanoparticles becomes crucial for mechanistic understanding and therapeutic applications of TiO2 NPs. In the present study, the effect of TiO2 NPs on native, unfolded, and misfolded luciferase has been investigated. TiO2 NPs were found to destabilize native luciferase, interfere with the spontaneous refolding of unfolded luciferase, and promote luciferase misfolding; however, minor structural alterations were observed indicating weak interactions between the TiO2 NPs and luciferase. Morphological analysis of TiO2 NPs showed an average size of 24.57 ± 4.94 nm that increased to 50.52 ± 16.71 nm upon adsorption of luciferase on to TiO2 NPs. This study provides an understanding on the implication of nanoparticle-protein interaction on structural and conformational changes in various protein conformers.