Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has not been completely defined in Babesia bovis. This study was focused on identifying the minimum B. bovis AMA-1-derived regions governing specific and high-affinity binding to its target cells. Different approaches were used for detecting ama-1 locus genetic variability and natural selection signatures. The binding properties of twelve highly conserved 20-residue-long peptides were evaluated using a sensitive and specific binding assay based on radio-iodination. B. bovis AMA-1 ectodomain structure was modelled and refined using molecular modelling software. NetMHCIIpan software was used for calculating B- and T-cell epitopes. The B. bovis ama-1 gene had regions under functional constraint, having the highest negative selective pressure intensity in the Domain I encoding region. Interestingly, B. bovis AMA-1-DI (¹⁰⁰YMQKFDIPRNHGSGIYVDLG¹¹⁹ and ¹²⁰GYESVGSKSYRMPVGKCPVV¹³⁹) and DII (³⁰²CPMHPVRDAIFGKWSGGSCV³²¹)-derived peptides had high specificity interaction with erythrocytes and bound to a chymotrypsin and neuraminidase-treatment sensitive receptor. DI-derived peptides appear to be exposed on the protein’s surface and contain predicted B- and T-cell epitopes. These findings provide data (for the first-time) concerning B. bovis AMA-1 functional subunits which are important for establishing receptor-ligand interactions which could be used in synthetic vaccine development.     

Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

Photocatalytic degradation of methylene blue and sulfisoxazole from water using biosynthesized zinc ferrite nanoparticles

The extensive occurrence of textile and pharmaceutical contaminants and their metabolites in water systems has posed significant concerns regarding their possible threat to human health and the environmental system. As a result, herein ZnFe₂O₄ nanoparticles were synthesized through the use of Monsonia burkeana plant extract. The synthesized nanoparticles were characterized using XRD, FTIR, UV–vis, SEM, EDS, TGA, BET, PL, EPR and VSM. XRD showed that the crystalline structure of ZnFe₂O₄ nanoparticles with a calculated crystal size of 25.03 nm was formed. FT-IR confirmed the characteristic functional groups contained within the M. burkeana plant were deposited on the formed ferrite nanoparticles. BET analysis confirmed the mesoporous nature of ZnFe₂O₄ with an average pore diameter of 31.6 nm. Morphological studies demonstrated that the formed nanoparticles had spherical as well as rod-like shapes. ZnFe₂O₄ photocatalyst illustrated that it may be effortlessly detached by an external magnetic field. The optimum conditions for the 99.8% removal of Methylene Blue was obtained at pH12, within 45min and at the optimum dosage of 25 mg of the catalyst. The as-prepared ZnFe₂O₄ nanoparticles proved to be easily separated and recycled, and remained efficient even after 5 reuses, proving that the material is highly stable. The ROS studies also demonstrated that electrons are the main factors contributing to the degradation of MB. Upon testing the photocatalytic performance of the sulfonamide antibiotic, sulfisoxazole in water showed a degradation of 67%. This study has shown that these materials can be used in targeting textile and pharmaceutically polluted water.     

Isolate-Specific Effect of Entomopathogenic Endophytic Fungi on Population Growth of Two-Spotted Spider Mite (Tetranychus urticae Koch) and Levels of Steroidal Glycoalkaloids in Tomato

Journal of Chemical Ecology - Entomopathogenic fungi (EPF) can be experimentally established in several plant species as endophytes. Ecological effects of EPF inoculations on plant growth and...     

The corrosion of mild and stainless steel in alkaline anaerobic conditions representing the Belgian “supercontainer” concept and the Swiss L/ILW repository

Deep geological repositories for radioactive waste contain metallic materials, either used to construct disposal canisters or as low-/intermediate-level waste (L/ILW). The safety relevance of corrosion is linked to canister lifetime in the former case and gas generation in the latter. More specifically, the Belgian “supercontainer” concept envisages mild steel for the used fuel disposal canister, and in the case of the Swiss L/ILW repository, mild steels are the largest metallic waste component due to the decommissioning of civilian power-generating facilities. For these circumstances, the corrosion environment is dominated by the chemistry of cement, which is used as buffer or backfill material. The corrosion behaviour of mild steel in anoxic environments was studied through the analysis of the hydrogen end-product. Hydrogen analysis was conducted by periodically purging the cell head-space and analysing the gas using a solid-state hydrogen sensor. While this method is limited to providing only uniform corrosion rates averaged over periods of time, ranging from weeks to months, it provides excellent resolution and sensitivity. The test cell environments were matched against the anticipated Belgian high-level waste and Swiss L/ILW repository environments, and also against experiments that have been conducted by other researchers for comparative purposes. Samples were exposed to synthetic cement pore waters, representing fresh and degraded cement. In young cement waters, the formation of initial corrosion products resulted in steel wire corrosion rates of the order of µm/year, which, at 80°C rapidly declined to ∼10 nm/year. In contrast, SA516 grade 70 steel plate corroded much more slowly under similar conditions. In aged cement waters, initial corrosion rates were higher but declined faster towards a longer-term rate of ∼10 nm/year. 316L stainless steel, embedded in cementitious material, corroded at a rate of <1 nm/year at 50°C.     

Vitamin A fortification: Recent advances in encapsulation technologies

Vitamin A is an essential micronutrient whose deficiency is still a major health concern in many regions of the world. It plays an essential role in human growth and development, immunity, and vision, but may also help prevent several other chronic diseases. The total amount of vitamin A in the human diet often falls below the recommended dietary allowance of approximately 900–1000 $\mu$g/day for a healthy adult. Moreover, a significant proportion of vitamin A may be degraded during food processing, storage, and distribution, thereby reducing its bioactivity. Finally, the vitamin A in some foods has a relatively low bioavailability, which further reduces its efficacy. The World Health Organization has recommended fortification of foods and beverages as a safe and cost-effective means of addressing vitamin A deficiency. However, there are several factors that must be overcome before effective fortified foods can be developed, including the low solubility, chemical stability, and bioavailability of this oil-soluble vitamin. Consequently, strategies are required to evenly disperse the vitamin throughout food matrices, to inhibit its chemical degradation, to avoid any adverse interactions with any other food components, to ensure the food is palatable, and to increase its bioavailability. In this review article, we discuss the chemical, physical, and nutritional attributes of vitamin A, its main dietary sources, the factors contributing to its current deficiency, and various strategies to address these deficiencies, including diet diversification, biofortification, and food fortification.     

Measuring the disparity among scientific disciplines using Library of Congress Subject Headings

Scientometrics - Examining the relationships among scientific disciplines is important today, but existing methods are limited by the contents and structure of their bibliographic databases. We...     

Optimization of flow in additively manufactured porous columns with graded permeability

Chemical engineering systems often involve a functional porous medium, such as in catalyzed reactive flows, fluid purifiers, and chromatographic separations. Ideally, the flow rates throughout the porous medium are uniform, and all portions of the medium contribute efficiently to its function. The permeability is a property of a porous medium that depends on pore geometry and relates flow rate to pressure drop. Additive manufacturing techniques raise the possibilities that permeability can be arbitrarily specified in three dimensions, and that a broader range of permeabilities can be achieved than by traditional manufacturing methods. Using numerical optimization methods, we show that designs with spatially varying permeability can achieve greater flow uniformity than designs with uniform permeability. We consider geometries involving hemispherical regions that distribute flow, as in many glass chromatography columns. By several measures, significant improvements in flow uniformity can be obtained by modifying permeability only near the inlet and outlet.     

Methodology for Estimating Streamflow by Water Balance and Rating Curve Methods Based on Logistic Regression

Both water balance (WB) and rating curve (RC) are methods for estimating streamflow. The first is mostly used to estimate reservoir outflows, while the second is usually adopted in hydrometeorological network streamflow gauges. While WB uses hourly collected data, the RC estimates streamflow using current water level and extrapolation techniques. The objective of this study was to analyze variations in the reservoir’s hourly outflow at Queimado Hydroelectric Power Plant (HPP Queimado) and to propose a method to evaluate whether the estimate of the daily outflows, obtained by the WB method, is similar to the flow values obtained at a conventional station. The logistic regression (LR) model was used because it is a method that adopts binary, categorically dependent variables to identify the event of interest. The results showed that the values of streamflow, obtained from an average of two daily readings, were a good representation of the flows in the region. The LR was able to identify atypical data, especially in the rainy season. This means that data consistency analysis can be faster and safer, when adequately employed and considering the proposed conditions, contributing to both management policies and the management of water resources.

     

Small-Molecule Inhibition of the uPAR ⋅ uPA Interaction by Conformational Selection

The urokinase receptor (uPAR) is a cell surface receptor that binds to the serine protease urokinase-type plasminogen activator (uPA) with high affinity. This interaction is beneficial for extravascular fibrin clearance, but it has also been associated with a broad range of pathological conditions including cancer, atherosclerosis, and kidney disease. Here, starting with a small molecule that we previously discovered by virtual screening and cheminformatics analysis, we design and synthesize several derivatives that were tested for binding and inhibition of the uPAR ⋅ uPA interaction. To confirm the binding site and establish a binding mode of the compounds, we carried out biophysical studies using uPAR mutants, among them uPAR^H47C−N259C, a mutant previously developed to mimic the structure of uPA-bound uPAR. Remarkably, a substantial increase in potency is observed for inhibition of uPAR^H47C−N259C binding to uPA compared to wild-type uPAR, consistent with our use of the structure of uPAR in its uPA-bound state to design small-molecule uPAR ⋅ uPA antagonists. Combined with the biophysical studies, molecular docking followed by extensive explicit-solvent molecular dynamics simulations and MM-GBSA free energy calculations yielded the most favorable binding pose of the compound. Collectively, these results suggest that potent inhibition of uPAR binding to uPA with small molecules will likely only be achieved by developing small molecules that exhibit high-affinity to solution apo structures of uPAR, rather than uPA-bound structures of the receptor.