Role of surface glycans in enveloped RNA virus infections: A structural perspective.

Enveloped RNA viruses have been causative agents of major pandemic outbreaks in the recent past. Glycans present on these virus surface proteins are critical for multiple processes during the viral infection cycle. Presence of glycans serves as a key determinant of immunogenicity, but intrinsic heterogeneity, dynamics, and evolutionary shifting of glycans in heavily glycosylated enveloped viruses confounds typical structure-function analysis. Glycosylation sites are also conserved across different viral families, which further emphasizes their functional significance. In this review, we summarize findings regarding structure-function correlation of glycans on enveloped RNA virus proteins.

Phosphorylation-Competent Metastable State of Escherichia coli Toxin HipA.

Phosphorylation is a key post-translational modification that alters the functional state of many proteins. The Escherichia coli toxin HipA, which phosphorylates glutamyl-tRNA synthetase and triggers bacterial persistence under stress, becomes inactivated upon autophosphorylation of Ser150. Interestingly, Ser150 is phosphorylation-incompetent in the crystal structure of HipA since it is deeply buried ("in-state"), although in the phosphorylated state it is solvent exposed ("out-state"). To be phosphorylated, a minor population of HipA must exist in the phosphorylation-competent "out-state" (solvent-exposed Ser150), not detected in the crystal structure of unphosphorylated HipA. Here we report a molten-globule-like intermediate of HipA at low urea (∼4 kcal/mol unstable than natively folded HipA). The intermediate is aggregation-prone, consistent with a solvent exposed Ser150 and its two flanking hydrophobic neighbors (Val/Ile) in the "out-state". Molecular dynamics simulations showed the HipA "in-out" pathway to contain multiple free energy minima with an increasing degree of Ser150 solvent exposure with the free energy difference between the "in-state" and the metastable exposed state(s) to be ∼2-2.5 kcal/mol, with unique sets of hydrogen bonds and salt bridges associated with the metastable loop conformations. Together, the data clearly identify the existence of a phosphorylation-competent metastable state of HipA. Our results not only suggest a mechanism of HipA autophosphorylation but also add to a number of recent reports on unrelated protein systems where the common proposed mechanism for phosphorylation of buried residues is their transient exposure even without phosphorylation.

Effect of biochar amendment on metal mobility, phytotoxicity, soil enzymes, and metal-uptakes by wheat (Triticum aestivum) in contaminated soils.

The use of low-cost substances such as biochar could be a sustainable approach to reduce the mobility, accumulation, and toxic impact of heavy metals in crop systems. This study investigates the effect of biochar amendment on heavy metal (Cr, Cd, Cu, Pb, Ni, Zn, Mg and Fe) mobility, bioaccumulation factor (BAF), plant (wheat) metal-uptake, plant oxidative stress, and soil enzymatic profile in contaminated industrial soil. Biochar was obtained from slow pyrolysis of Lantana (LBC), and Parthenium (PBC) biomass, and applied at 3% rates in contaminated soils for wheat crop study under a greenhouse experimental setup. Results show in comparison with control setups, low mobility of Cr (14.15-16.35%), Cd (7.17-15.24%), Cu (9.81-12.97%), Pb (7.99-15.23%), Ni (1.52-2.38%), Zn (10.47-14.42%), Mg (48.85-52.89%), and Fe (19.13-19.90%) contents in soils. The heavy metal uptake rates were 63.08% (Cr), 78.07% (Cd), 74.61% (Cu), 78.11% (Pb), 75.73% (Ni), 69.71% (Zn), 28.78% (Mg), and 49.26% (Fe) lower in biochar amendments, compared with the control treatments. Similarly, the biochar amended treatments exhibited low oxidative stress in wheat plants than control setups. In addition, soil enzymes (dehydrogenase, ß-glucosidase, alkaline phosphatase, and urease) alleviated in biochar amended soils indicating reduced toxicity of metals in experimental soils. In summary, this study indicates that biochar amendment in contaminated soils not only improves plant growth but also lowers the rates of soil and plant toxicity and metal bioavailability as well.

Estimation of production cross-sections, transmutation and gas generation from radionuclides (A ∼50-60) in fusion environment.

Degradation of material properties under neutron irradiation generates a requirement for studying effects on materials in a fusion environment and optimizing radiation-resistant materials for future applications. In the present work, the durability of stainless steel (SS) alloy used in ITER-like fusion devices is studied. We have predicted the amount of radionuclides produced in the material upon neutron irradiation at various locations is determined using the ACTYS, neutron activation code, for a typical one-dimensional geometry of ITER-like fusion reactor. The ACTYS code is further used to determine the gas production from 55Fe, 59Ni, and other long-lived radionuclides in the material. To further stress the importance of gas production in fusion materials, a comparative study of gas production cross-sections as given in various standard data libraries is examined using TALYS-1.8 and is presented in the paper.

Insights on the disruption of the complex between human positive coactivator 4 and p53 by small molecules.

Interaction between human positive coactivator 4 (PC4), an abundant nuclear protein, and the tumor suppressor protein p53 plays a crucial role in initiating apoptosis. In certain neurodegenerative diseases PC4 assisted-p53-dependent apoptosis may play a central role. Thus, disruption of p53-PC4 interaction may be a good drug target for certain disease pathologies. A p53-derived short peptide (AcPep) that binds the C-terminal domain of PC4 (C-PC4) is known to disrupt PC4-p53 interaction. To fully characterize its binding mode and binding site on PC4, we co-crystallized C-PC4 with the peptide and determined its structure. The crystal, despite exhibiting mass spectrometric signature of the peptide, lacked peptide electron density and showed a novel crystal lattice, when compared to C-PC4 crystals without the peptide. Using peptide-docked models of crystal lattices, corresponding to our structure and the peptide-devoid structure we show the origin of the novel crystal lattice to be dynamically bound peptide at the previously identified putative binding site. The weak binding is proposed to be due to the lack of the N-terminal domain of PC4 (N-PC4), which we experimentally show to be disordered with no effect on PC4 stability. Taking cue from the structure, virtual screening of ∼18.6 million small molecules from the ZINC15 database was performed, followed by toxicity and binding free energy filtering. The novel crystal lattice of C-PC4 in presence of the peptide, the role of the disordered N-PC4 and the high throughput identification of potent small molecules will allow a better understanding and control of p53-PC4 interaction.

Phytotoxicity and degradation of antibiotic ofloxacin in duckweed (Spirodela polyrhiza) system.

The phytotoxicity and degradation of ofloxacin (OFX) in duckweed Spirodela polyrhiza based system was estimated in this study. For that, OFX was added in an environmentally relevant range (0.01-1.0 mg L-1) in medium (Hoagland nutrient) and toxicity biomarkers, i.e. changes in plant biomass, relative growth rate (RGR), photopigment (Chl-a, Chl-b and carotenoids), protein content, antioxidative enzymes (catalase, CAT; superoxide dismutase, SOD; and ascorbate peroxidases, APX) in fronds were estimated. The batch-scale setups (250 ml) was prepared in triplicate for each concentration of OFX and reared in growth chambers (Algae Tron AG 230) for 7 d. Results suggested that the high concentrations of OFX caused a reduction in biomass (4.8-41.3%), relative root growth (RGR), protein (4.16-11.28%) and photopigment contents. The fronds in OFX spiked setups showed an increased level of antioxidative enzymes: CAT (0.230-0.338 mmolH2O2 mg-1 protein), APX (0.043-0.074 mmolascorbate mg-1 protein), and SOD (0.267-0.317 U mg-1 protein) than control. At the end (7 d), the residual OFX content in the medium was also estimated, and results suggested a significant (p < 0.05) reduction (93.73-98.36%) in OFX content than control setup (54.76-75.53%) at the end of the experimentation. The trend of residual OFX suggested phytodegradation as a significant mechanism of antibiotic degradation other than hydrolysis and photodegradation processes. This study indicates that duckweed can be an effective bio-tool for the removal of environmental relevant concentration of the antibiotics from the wastewater.

Phytotoxicity of amoxicillin to the duckweed Spirodela polyrhiza: Growth, oxidative stress, biochemical traits and antibiotic degradation.

The increasing availability of antibiotics in wastewater has created a serious threat to non-target organisms in the environment. The aim of this study was to evaluate the potential toxicity of amoxicillin on duckweed Spirodela polyrhiza during a short-term exposure (7 d). The duckweed was exposed to a range of environmentally relevant (0.0001-0.01 mg L-1) and high (0.1 and 1 mg L-1) concentrations of amoxicillin. Subsequently, biomarkers of toxicity such as growth, pigments (Chl a, Chl b and carotenoids), antioxidative enzyme activity (catalase, CAT; superoxide dismutase, SOD; and ascorbate peroxidases, APX), and biochemical content (protein, lipid and starch) were analysed in their fronds. The high dose (1 mg L-1) of amoxicillin caused a significant (p < 0.05) decrease in photopigments, protein, starch and lipid content and an increase in carotenoids/total Chl and Chl a/Chl b ratios in fronds of Spirodela polyrhiza. The results showed a shift in biomarkers: a decrease in frond growth and relative growth rate (RGR) (16.2-53.8%) and an increase in the activities (mmol mg protein-1) of CAT (0.021-0.041), APX (0.84-2.49) and SOD (0.12-0.23) in fronds. The significantly (p < 0.05) greater reduction in amoxicillin content in duckweed setups (84.6-100%) than in the control (62.1-73%) suggested that phytodegradation is an important mechanism in removing antibiotics from water, apart from hydrolysis and photodegradation, which occur in control setups. Overall, the results suggested a toxic effect of amoxicillin on Spirodela polyrhiza, even at low concentrations, and nonetheless, the duckweed contributed directly to the degradation of antibiotics in the water and throughout the phytoremediation process.

Investigation of (n, p), (n, 2n) reaction cross sections for Sn isotopes for fusion reactor applications.

The compound Nb3Sn possess superconductivity at suitable temperatures, therefore, it is best suited to be used in the toroidal coils of superconducting magnets which holds the fusion plasma and confine it inside the reactor core. The neutron induced reaction cross-sections are required from threshold to 20MeV for different isotopes of Tin (Sn). Since limited data is available for the reactions with the Sn isotopes. Therefore, we have optimized the (n, p) and (n, 2n) reaction cross-sections for all possible Sn isotopes from threshold to 20MeV with modified input parameters in the nuclear reaction modular codes EMPIRE-3.2.2 and TALYS-1.8. These codes account for the major nuclear reaction mechanisms, including direct, pre-equilibrium, and compound nucleus contributions. The present results from 116Sn(n,p)116mIn, , 117Sn(n,p)117mIn, 118Sn(n,2n)117mSn,120Sn(n,2n)119mSn and 124Sn(n,2n)123mSn reactions calculated with nuclear modular codes: TALYS - 1.8, EMPIRE - 3.2.2 were compared with EXFOR data, systematics proposed by several authors and with the existing evaluated nuclear data library ENDF/B-VII.1, as well. The results from the present study can be used for the future development of ITER devices as well as to upgrade the nuclear model codes.

Nutrient changes and biodynamics of Eisenia fetida during vermicomposting of water lettuce (Pistia sp.) biomass: a noxious weed of aquatic system.

This paper reports the results of vermicomposting of water lettuce biomass (WL) spiked with cow dung at ratios of 20, 40, 60, and 80 % employing Eisenia fetida. A total of four treatments were established and changes in chemical properties of mixtures were observed. Vermicomposting caused a decrease in pH, TOC, volatile solids, and C/N ratio by 1.01-1.08-fold, 0.85-0.92-fold, 0.94-0.96-fold, 0.56-0.70-fold, respectively, but increase in EC, totN, totP, totK, totCa, totZn, totFe, and totCu, by 1.19-1.42-fold, 1.33-1.68-fold, 1.38-1.69-fold, 1.13-1.24-fold, 1.04-1.11-fold, 1.16-1.37-fold, 1.05-1.113-fold, 1.10-1.27-fold, respectively. Overall, the treatment with 60-80 % of WL showed the maximum decomposition and mineralization rates. The earthworm showed the growth and reproduction rate in considerable ranges in all treatment setups but setups with 60-80 % WL proportion exhibited the optimum results. Results reveal that biomass of water lettuce can be utilized effectively for production of valuable manure through vermicomposting system.

Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells.

BACKGROUND: Mesoporous silica nanoparticles (MSNs) have been promising vehicles for drug delivery. Quercetin (Q), a natural flavonoid, has been reported to have many useful effects. However, poor water solubility as well as less bioavailability has confined its use as a suitable anti-cancer drug. Therefore, profound approach is required to overcome these drawbacks. METHODS: We have synthesized folic acid (FA) armed mesoporous silica nanoparticles (MSN-FA-Q) loaded with quercetin and then characterized it by DLS, SEM, TEM and FTIR. MTT, confocal microscopy, flow cytometry, scratch assay and immunoblotting were employed to assess the cell viability, cellular uptake, cell cycle arrest, apoptosis, wound healing and the expression levels of different signalling molecules in breast adenocarcinoma cells. Nanoparticle distribution was investigated by using ex vivo optical imaging and CAM assay was employed to assess tumor regression. RESULTS: MSN-FA-Q facilitates higher cellular uptake and allows more drug bioavailability to the breast cancer cells with over-expressed folate receptors. Our experimental results suggest that the newly synthesized MSN-FA-Q nanostructure caused cell cycle arrest and apoptosis in breast cancer cells through the regulation of Akt & Bax signalling pathways. Besides, we also observed that MSN-FA-Q has a concurrent anti-migratory role as well. CONCLUSION: This uniquely engineered quercetin loaded mesoporous silica nanoparticle ensures a targeted delivery with enhanced bioavailability. GENERAL SIGNIFICANCE: Effective targeted therapeutic strategy against breast cancer cells.

Neutron activation cross-sections for Ytterbium isotopes at (14.6±0.3)MeV.

The cross-sections of (nat)Yb (n,x)(172,173) Tm, (174)Yb(n,p) (174) Tm, (174)Yb (n,α) (171)Er, (176)Yb(n,p) (176) Tm, (176)Yb(n,α)(173) Er, and (176) Yb(n,n')(176m)Yb have been measured at 14.6±0.3MeV neutron energy, among them two cross-sections (nat)Yb (n,x)(172,173)Tm are reported for the first time. These experimental cross-sections are compared with experimental data found in the literature, with evaluated nuclear data in JENDL-4.0 and TENDL-2010 libraries and with theoretically calculated values based on nuclear reaction modular codes EMPIRE-3.0 and TALYS-1.2.