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1.
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.  相似文献   
2.
Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.  相似文献   
3.
Artificial domestication and improvement of the majority of crops began approximately 10,000 years ago, in different parts of the world, to achieve high productivity, good quality, and widespread adaptability. It was initiated from a phenotype-based selection by local farmers and developed to current biotechnology-based breeding to feed over 7 billion people. For most cereal crops, yield relates to grain production, which could be enhanced by increasing grain number and weight. Grain number is typically determined during inflorescence development. Many mutants and genes for inflorescence development have already been characterized in cereal crops. Therefore, optimization of such genes could fine-tune yield-related traits, such as grain number. With the rapidly advancing genome-editing technologies and understanding of yield-related traits, knowledge-driven breeding by design is becoming a reality. This review introduces knowledge about inflorescence yield-related traits in cereal crops, focusing on rice, maize, and wheat. Next, emerging genome-editing technologies and recent studies that apply this technology to engineer crop yield improvement by targeting inflorescence development are reviewed. These approaches promise to usher in a new era of breeding practice.  相似文献   
4.
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 Å2 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 Poct-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.  相似文献   
5.
Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different “sensitizing ratio”. Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.  相似文献   
6.
Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.  相似文献   
7.
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.  相似文献   
8.
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...  相似文献   
9.
Distillers grains and solubles generated from the ethanol fermentation of grains contain acylglycerols (AG) that can be successfully converted to fatty acid methyl esters (FAME) and fatty acid ethyl esters (FAEE), commonly known as biodiesel. However, when grain sorghum (milo) DDGS were used as a feedstock for in situ transesterification (IST) under the previously established optimal conditions for other AG-bearing substrates, the yield plateaued at only 32.2% (corrected in this study to 24.2%). Several IST studies have reported significantly higher conversions of AG-bearing substrates to FAME. Therefore, the goal of this IST study was to improve the conversion of the AG in milo DDGS to FAME and FAEE by varying the temperature of reaction, the concentrations of the base (sodium methylate, NaOMe), volume of methanol and ethanol, and the amount of moisture in DDGS. Methyl tert-butyl ester was also evaluated as a co-solvent intended to improve miscibility and reaction rate. Among these variables, the most effective change was an increase in temperature from 40 to 65 °C. The most successful reaction used a AG:NaOMe:MeOH molar ratio of 1.0:2.6:168.9. Those reaction conditions used 4.8 mmol NaOMe dissolved in 12.6 mL MeOH and resulted in a 79.8% conversion of AG to FAME.  相似文献   
10.
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 μ $ \umu $ 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.  相似文献   
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