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951.
Jarrad M. Altimari Samantha C. Hockey Dr. Helena I. Boshoff Dr. Andaleeb Sajid Dr. Luke C. Henderson 《ChemMedChem》2015,10(5):787-791
Tuberculosis (TB) remains a pressing unmet medical need, particularly with the emergence of multidrug‐resistant and extensively drug‐resistant tuberculosis. Here, a series of 1,4‐substituted‐1,2,3‐triazoles have been synthesized and evaluated as potential antitubercular agents. These compounds were assembled via click chemistry in high crude purity and in moderate to high yield. Of the compounds tested, 12 compounds showed promising antitubercular activity with six possessing minimum inhibitory concentration (MIC) values <10 μg mL?1, and total selectivity for Mycobacterium tuberculosis (Mtb) growth inhibition. A second set of 21 compounds bearing variations on ring C were synthesized and evaluated. This second library gave an additional six compounds displaying MIC values ≤10 μg mL?1 and total selectivity for Mtb growth inhibition. These compounds serve as an excellent starting point for further development of antitubercular therapies. 相似文献
952.
Autism spectrum disorders are a group of mental illnesses highly correlated with gastrointestinal dysfunction. Recent studies have shown that there may be one or more microbial “fingerprints” in terms of the composition characterizing individuals with autism, which could be used for diagnostic purposes. This paper proposes a computational approach whereby metagenomes characteristic of “healthy” and autistic individuals are artificially constructed via genomic information, analyzed for the enzymes coded within, and then these enzymes are compared in detail. This is a text mining application. A custom-designed online application was built and used for the comparative metabolomics study and made publically available. Several of the enzyme-catalyzing reactions involved with the amino acid glutamate were curiously missing from the “autism” microbiome and were coded within almost every organism included in the “control” microbiome. Interestingly, there exists a leading hypothesis regarding autism and glutamate involving a neurological excitation/inhibition imbalance; but the association with this study is unclear. The results included data on the transsulfuration and transmethylation pathways, involved with oxidative stress, also of importance to autism. The results from this study are in alignment with leading hypotheses in the field, which is impressive, considering the purely in silico nature of this study. The present study provides new insight into the complex metabolic interactions underlying autism, and this novel methodology has potential to be useful for developing new hypotheses. However, limitations include sparse genome data availability and conflicting literature experimental data. We believe our software tool and methodology has potential for having great utility as data become more available, comprehensive and reliable. 相似文献
953.
Thermal and chemical stabilization of ethylene/vinyl acetate/vinyl alcohol (EVA‐OH) terpolymers under nitroplasticizer environments 下载免费PDF全文
In this study, we compare the aging behaviors of cross‐linked ethylene/vinyl acetate/vinyl alcohol terpolymers, also referred to as EVA‐OH, when they are either immersed in nitroplasticizer (NP) liquid or exposed to NP vapor at different temperatures. While thermogravimetric analysis and differential scanning calorimetry are used to probe the thermal stability of aged NP and polymers, Fourier transform infrared, gel permeation chromatography, ultra‐violet/vis, and nuclear magnetic resonance are used to probe their structural changes over the aging process. The study confirms that NP degrades through C? N cleavage, and releases HONO molecules at a slightly elevated temperature (<75°C). As these molecules accumulate in the vapor phase, they react among themselves to create an acidic environment. Therefore, these chemical constituents in the NP vapor significantly accelerate the hydrolysis of EVA‐OH polymer. When the hydrolysis occurs in both vinyl acetate and urethane groups and the scission at the cross‐linker progresses, EVA‐OH becomes vulnerable to further degradation in the NP vapor environment. Through the comprehensive characterization, the possible degradation mechanisms of the terpolymers are proposed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41450. 相似文献
954.
Sin-Lih Tan Muruj Barri Peace Atakpa-Adaji Colin W. Taylor Ewan St. John Smith Ruth D. Murrell-Lagnado 《International journal of molecular sciences》2021,22(19)
The P2X4 purinergic receptor is targeted to endolysosomes, where it mediates an inward current dependent on luminal ATP and pH. Activation of P2X4 receptors was previously shown to trigger lysosome fusion, but the regulation of P2X4 receptors and their role in lysosomal Ca2+ signaling are poorly understood. We show that lysosomal P2X4 receptors are activated downstream of plasma membrane P2X7 and H1 histamine receptor stimulation. When P2X4 receptors are expressed, the increase in near-lysosome cytosolic [Ca2+] is exaggerated, as detected with a low-affinity targeted Ca2+ sensor. P2X4-dependent changes in lysosome properties were triggered downstream of P2X7 receptor activation, including an enlargement of lysosomes indicative of homotypic fusion and a redistribution of lysosomes towards the periphery of the cell. Lysosomal P2X4 receptors, therefore, have a role in regulating lysosomal Ca2+ release and the regulation of lysosomal membrane trafficking. 相似文献
955.
Ngila M. P. S. Ricardo Andrew Glendinning Colin Price 《Polymer Engineering and Science》1996,36(2):182-187
We report on the synthesis of non-ionic surfactants via the Koenigs-Knorr reaction with chemical structures GOR and GOPOG, where GO(H) is glucose, R is n-decyl or n-dodecyl, and P is polyoxypropylene or polycaprolactone. Surface properties were studied using a Cenco-du-Nouy tensiometer. Light and transmission electron microscopy were used to investigate the phase behavior of the surfactants over a range of concentrations. AOR surfactants, where A is the product of amylose degradation and R is decyl, were synthesized by an alcohol exchange procedure. 相似文献
956.
Dr. Yannick Pauchet Dr. Colin Ruprecht Dr. Fabian Pfrengle 《Chembiochem : a European journal of chemical biology》2020,21(10):1517-1525
Xylophagous long-horned beetles thrive in challenging environments. To access nutrients, they secrete plant-cell-wall-degrading enzymes in their gut fluid; among them are cellulases of the subfamily 2 of glycoside hydrolase family 5 (GH5_2). Recently, we discovered that several beetle-derived GH5_2s use xylan as a substrate instead of cellulose, which is unusual for this family of enzymes. Here, we analyze the substrate specificity of a GH5_2 xylanase from the beetle Apriona japonica (AJAGH5_2-1) using commercially available substrates and synthetic arabinoxylan oligo- and polysaccharides. We demonstrate that AJAGH5_2-1 processes arabinoxylan polysaccharides in a manner distinct from classical xylanase families such as GH10 and GH11. AJAGH5_2-1 is active on long oligosaccharides and cleaves at the non-reducing end of a substituted xylose residue (position +1) only if: 1) three xylose residues are present upstream and downstream of the cleavage site, and 2) xylose residues at positions −1, −2, +2 and +3 are not substituted. 相似文献
957.
English Andrew C.; Groom Colin R.; Hubbard Roderick E. 《Protein engineering, design & selection : PEDS》2001,14(1):47-59
Multiple Solvent Crystal Structures (MSCS) is a crystallographictechnique to identify energetically favorable positions andorientations of small organic molecules on the surface of proteins.We determined the high-resolution crystal structures of thermolysin(TLN), generated from crystals soaked in 5070% acetone,5080% acetonitrile and 50 mM phenol. The structures ofthe protein in the aqueousorganic mixtures are essentiallythe same as the native enzyme and a number of solvent interactionsites were identified. The distribution of probe molecules showsclusters in the main specificity pocket of the active site anda buried subsite. Within the active site, we compared the experimentallydetermined solvent positions with predictions from two computationalfunctional group mapping techniques, GRID and Multiple CopySimultaneous Search (MCSS). The experimentally determined smallmolecule positions are consistent with the structures of knownproteinligand complexes of TLN. 相似文献
958.
The organocatalyzed aminolysis of cyclic carbonates to form (poly)hydroxyurethanes is an important reaction as an alternative to isocyanate based chemistries. In an effort to increase reaction rates between cyclic carbonates and amines to lower cure times and increase molecular weights, various organocatalysts were surveyed. Reaction rates between monofunctional model cyclic carbonates and amines were determined in the presence of a variety of organocatalysts, which operate under different mechanisms to promote the reaction. Of the catalysts investigated, TBD was the most potent, presumably due to its bifunctional activity. TBD was also used to promote step-growth polymerization between difunctional cyclic carbonates and amines. The polymers produced in the presence of TBD at room temperature were much higher in molecular weight than polymers produced in the absence of catalyst at both room temperature and at 80 °C. 相似文献
959.
The abatement of NH3 from waste streams has become an important environmental issue. Selective catalytic oxidation (SCO) of NH3 to N2 has emerged as a potential technology for taking care of NH3 slips and NH3 in waste streams. In this work, we describe the catalytic activity of Fe-zeolite catalysts prepared by incipient wetness technique, ion exchange and hydrothermal synthesis in the SCO of NH3 to N2 using a fixed bed flow reactor. Selective catalytic oxidation was carried out at 573–723 K and 105 Pa with gas hourly space velocities (GHSV) between 24 000 and 240 000 h−1. Results obtained showed that Fe-ZSM-5 catalysts prepared by incipient wetness technique were active for NH3 conversion (77–100%) and selectivity to N2 (65–100%). Fe-ASA and Fe-Beta showed good catalytic activity and selectivity, but their activity and selectivity were less than that of Fe-ZSM-5. The effects of water vapour, Fe loading, and activation method on the performance of these catalysts was also investigated. 相似文献
960.
MM Aarts D Levy B He S Stregger T Chen S Richard JE Henderson 《Canadian Metallurgical Quarterly》1999,274(8):4832-4838
Parathyroid hormone-related protein (PTHrP) is a secreted protein that acts as an autocrine and paracrine mediator of cell proliferation and differentiation. In addition to its biological activity that is mediated through signal transduction cascades, there is evidence for an intracellular role for PTHrP in cell cycle progression and apoptosis. These effects are mediated through a mid-region nuclear targeting sequence (NTS) that localizes PTHrP to the region of the nucleolus where ribonucleoprotein complexes form in vivo. In this work, we show that endogenous, transfected, and in vitro translated PTHrP proteins bind homopolymeric and total cellular RNAs at salt concentrations up to 1 M. A peptide representing the PTHrP NTS was effective in competing with the wild-type protein for RNA binding, whereas a similar peptide representing the nucleolin NTS was not. Site-directed mutagenesis revealed that the binding of PTHrP to RNA was direct and was dependent on preservation of a core GXKKXXK motif, embedded in the PTHrP NTS, which is shared with other RNA-binding proteins. The current observations are the first to document RNA binding by a secreted cellular protein and predict a role for PTHrP in regulating RNA metabolism that may be related to its localization in the nucleolus of cells in vivo. 相似文献