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931.
In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a─q) were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of Aβ aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate anti-oxidant activity and strong neuroprotective capacities, and accelerated dosage-dependently the Aβ aggregation. Also, we presented here a complete study on the interaction of 8a, 8d, 8e, 8h and 8i with AChE. Through fluorescence emission studies, the binding sites number found to be 1, binding constants were calculated as 2.04 × 104, 2.22 × 104, 1.18 × 104, 9.8 × 103 and 3.2 × 104 M−1 and free energy change as −5.83, −5.91, −5.51, −5.41 and −6.12 kcal M−1 at 25 °C which were well agreed with the computational calculations indicating a strong binding affinity of flavones and AChE. Furthermore, the CD studies revealed that the secondary structure of AChE became partly unfolded upon binding with 8a, 8d, 8e, 8h and 8i. 相似文献
932.
J. E. Higgins 《Biometrical journal. Biometrische Zeitschrift》1981,23(2):185-198
A model is discussed for incorporating information from a time-dependent covariable (an intervening event) and covariables independent of time into the analysis of survival data. In the model, it is assumed that individuals are potentially subject to two paths to failure, one including the intervening event and the other not. Additional assumptions are that failure times associated with the two paths are independent and that the time to failure subsequent to the intervening event is dependent on the intervening event time. Allowing the underlying hazard rates for the model to follow a WEIBULL form, use of the model and methods for fitting and hypothesis testing are illustrated by application to a follow-up study involving industrial workers where disability retirement was the intervening event. Extensions of the model to accommodate grouped survival data are presented. 相似文献
933.
When CaCl2 was added in increasing concentrations to a rat liver metabolic activation system (S9) buffered with sodium phosphate, the mutagenic activity and cytotoxicity of dimethylnitrosamine (DMN) in the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) system were greatly increased. This effect was not observed with an S9 mix buffered with N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES). The calcium phosphate gel precipitate of the S9 mix possessed approximately of the total activity of the mix, while the supernatant had only slight activity. However, when the calcium phosphate gel precipitate of a solution of S9 salts (without S9 protein) was added to the supernatant, the remaining of the activity was recovered. Commercially obtained calcium phosphate, tricalcium phosphate, and alumina C γ gels could substitute for CaCl2 in the S9 mix, but diethylaminoethyl cellulose (DEAE cellulose) could not. Alumina C γ gel can exert its effect in the absence of both CaCl2 and phosphate in the S9 mix. Increasing the time of contact between the S9 protein and the S9 salts increased the efficacy with which the S9 mix activated DMN; this is indicative of an adsorptive process by calcium phosphate gel. 相似文献
934.
935.
Weanling rats were fed diets either alone or with combinations of silver, elevated zinc, or elevated cadmium for 7 weeks.
The rats were then killed, and the silver, zinc, and cadmium proteins isolated from the livers by gel filtration and ion exchange
chromatography. When silver was fed alone in diet, low levels of this metal were eluted as two peaks from the ion exchange
column. In contrast, when silver was fed with cadmium or elevated zinc, three metal-containing peaks were eluted from this
ion exchange column. Amino acid analysis revealed that the major proteins binding these metals are metallothioneins, as judged
by high cysteine content. 相似文献
936.
937.
Tatyana Borodianskiy-Shteinberg Inna KaltSarit Kipper Nofar NachumShiri Katz Maor H. PaukerMira Barda-Saad Doron GerberRonit Sarid 《Journal of molecular biology》2014
The human “protein interacting with carboxyl terminus 1” (PICT-1), also designated as the “glioma tumor suppressor candidate region 2 gene product”, GLTSCR2, is a nucleolar protein whose activity is, as yet, unknown. Contradictory results regarding the role of PICT-1 in cancer have been reported, and PICT-1 has been suggested to function either as a tumor suppressor protein or as an oncogene. In this study, we demonstrate self-association of PICT-1. Through yeast two-hybrid assay, we identified PICT-1 as its own interaction partner. We confirmed the interaction of PICT-1 with itself by direct yeast two-hybrid assay and also showed self-association of PICT-1 in mammalian cells by co-immunoprecipitation and fluorescence resonance energy transfer assays. Furthermore, we confirmed direct self-association of PICT-1 by using in vitro microfluidic affinity binding assays. The later assay also identified the carboxy-terminal domain as mediating self-interaction of PICT-1. Glutaraldehyde cross-linking and gel-filtration assays suggest that PICT-1 forms dimers, though it may form higher-order complexes as well. Our findings add another layer of complexity in understanding the different functions of PICT-1 and may help provide insights regarding the activities of this protein. 相似文献
938.
939.
The present study aims to investigate small RNA interactions with putative disease response genes in the model grass species Brachypodium distachyon. The fungal pathogen Fusarium culmorum (Fusarium herein) and phytohormone salicylic acid treatment were used to induce the disease response in Brachypodium. Initially, 121 different putative disease response genes were identified using bioinformatic and homology based approaches. Computational prediction was used to identify 33 candidate new miRNA coding sequences, of which 9 were verified by analysis of small RNA sequence libraries. Putative Brachypodium miRNA target sites were identified in the disease response genes, and a subset of which were screened for expression and possible miRNA interactions in 5 different Brachypodium lines infected with Fusarium. An NBS-LRR family gene, 1g34430, was polymorphic among the lines, forming two major genotypes, one of which has its miRNA target sites deleted, resulting in altered gene expression during infection. There were siRNAs putatively involved in regulation of this gene, indicating a role of small RNAs in the B. distachyon disease response. 相似文献
940.
Debbie C. Crans 《Molecular Engineering》1993,3(1-3):277-284
The interactions of phosphoglucose isomerase with solutions of rapidly interconverting oxovanadates are described. Quantitative speciation analyses of vanadate monomer, dimer, tetramer and pentamer were performed under the conditions of the enzyme assay. 2D EXSY51V NMR spectroscopy was used to demonstrate that the oligoanions are sufficiently long-lived to be recognized by the enzyme as different species. The observations are consistent with the vanadate tetramer being responsible for the observed inhibition. Selected oxomolybdates ([(CH3)2AsMo4OH]2– and [(NH3C2H4P)2Mo5O21]2–) were also found to inhibit 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, glycerol-3-phosphate dehydrogenase and fructose-1,6-bisphosphate aldolase. The selectivities and affinities of these proteins for the oxometalates are discussed. 相似文献