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《Bioorganic & medicinal chemistry letters》2014,24(5):1280-1284
A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain. 相似文献
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Abstract: Age-related changes in the expression of Na,K-ATPase α1- and α3-isoform mRNAs were analyzed by in situ hybridization in the Fischer-344 rat hippocampus. Quantification of signal density with cRNA probes in rat hippocampus at 3 months of age showed (a) α1 content is 1.5 times higher in granule than in pyramidal cell layers, whereas α3 content shows the opposite ratio and (b) α3 label is found in large clusters related to mossy cells and basket cells and in medium clusters corresponding to interneurons within the dendritic fields of CA1–3. In the 24-month-old rats as compared with the young animals, the α1 signal is increased more than sevenfold in the dendritic fields and is not significantly changed in perikaryal layers. The α3 signal is reduced about threefold ( p < 0.0001, ANOVA, n = 6) in perikaryal layers, is almost completely absent over the interneurons, basket cells, and mossy cells, and is not significantly changed in dendritic fields. These data indicate age-related, cell- and isoform-specific alterations in pretranslational regulation of Na,K-ATPase α isoforms. The striking changes in the dendritic fields, mossy cells, and GABAergic basket cells and interneurons may constitute early and sensitive markers for age-related alterations in hippocampal function, before cell loss. 相似文献
14.
4-Phenylylboronic acid enhances the light emission from the horseradish peroxidase catalysed oxidation of luminol by hydrogen peroxide. Optimization studies showed that the greatest enhancement was obtained using micromolar concentrations of the new enhancer. The largest degree of enhancement was found with the basic isoenzyme of horseradish peroxidase (Type VIA), and lesser degrees of enhancement were obtained with Type VII and Type IX horseradish peroxidase. The enhancer was also effective in the peroxidase catalysed oxidation of isoluminol by peroxide. 相似文献
15.
Summary The location, number and size of the motoneurons innervating the ischiocavernosus muscle, identified by means of horseradish-peroxidase (HRP) retrograde transport, were studied (1) in adult untreated male rats, (2) in adult male rats castrated before puberty, and (3) in adult male rats castrated before puberty and injected with testosterone from the day of castration. After injection of HRP into the ischiocavernosus muscle, labeled motoneurons were found in the dorsolateral and dorsomedial columns of the lamina IX, at the level of L6 and S1 segments of the spinal cord. Morphometric analysis demonstrated that prepubertal castration induces a statistically significant reduction in the somatic and nuclear areas (40% and 35%, respectively, if compared to those of the control rats) of both the dorsolateral and dorsomedial motoneurons, but does not affect their number. The effects of castration are prevented by exogenous testosterone.Preliminary results were presented at the International Conference on Hormones, Brain and Behaviour, Liège, Belgium, August, 1989 相似文献
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The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC50 values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC50 > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549. 相似文献
18.
1. Insect galls are abnormal plant growths that develop in response to a stimulus provided by a galling insect. The nutrition hypothesis suggests that the concentrations of nutritive compounds in galls are changed to provide optimum nutrition for the larvae and adults of galling insects. 2. To test the nutrition hypothesis, we determined the concentrations of 20 free amino acids in galls and in galled and ungalled twigs of Quercus fabri during the larval and adult stages of Andricus mukaigawae using high-performance liquid chromatography with ultraviolet–visible detection. 3. At the larval stage, the concentrations of 12 out of 20 amino acids in A. mukaigawae galls were significantly higher than those in galled and ungalled twigs. Asparagine and tryptophan were the most abundant nonessential and essential amino acids, respectively, in A. mukaigawae galls. 4. At the adult stage, the concentrations of most amino acids, except proline, were significantly lower in A. mukaigawae galls than in galled and ungalled twigs. The A. mukaigawae adults may not manipulate amino acid levels because the adults do not feed on galls. The decrease of amino acid levels in adult galls may be viewed as a depletion. 5. The composition of free amino acids in A. mukaigawae galls was significantly different from the composition in galled and ungalled twigs in both the larval and adult stages. 6. Our results may support the nutrition hypothesis. We suggest that a high concentration of proline in A. mukaigawae galls may protect larvae and adults from plant defense responses. 相似文献
19.
A. Rigotto S.R. Cotta A.C.F. Dias J.L.N. Carvalho F.D. Andreote 《Letters in applied microbiology》2020,71(5):444-450
Sugarcane cultivation supports Brazil as one of the largest world sugar and ethanol producer. In order to understand the impact of changing sugarcane harvest from manual to mechanized harvest, we studied the effect of machinery traffic on soil and consequently soil compaction upon soil microbial communities involved in nitrogen cycling. The impact of sugarcane harvest was dependent on soil depth and texture. At deeper soil layers, mechanized harvesting increases the abundance of nitrogen fixers and denitrifying communities (specifically nosZ clade I and II) while manual harvesting increases the abundance of ammonia oxidizers (specifically AOA) and increases denitrifying communities (nosZ clade I and II) on top and at intermediate depth. The effect of change on the harvest system is more evident on sandy soil than on clay soil, where soil indicators of compaction (bulk density and penetration resistance) were negatively correlated with soil microorganisms associated with the nitrogen cycle. Our results point to connections between soil compaction and N transformations in sugarcane fields, besides naming biological variables to be used as proxies for alterations in soil structure. 相似文献
20.
Honghong Yang Yuanyuan Zhang Zhihai Wang Shixun Zhong Guohua Hu Wenqi Zuo 《Bioelectromagnetics》2020,41(3):219-229
To investigate the possible mechanisms for biological effects of 1,800 MHz mobile radiofrequency radiation (RFR), the radiation-specific absorption rate was applied at 2 and 4 W/kg, and the exposure mode was 5 min on and 10 min off (conversation mode). Exposure time was 24 h short-term exposure. Following exposure, to detect cell DNA damage, cell apoptosis, and reactive oxygen species (ROS) generation, the Comet assay test, flow cytometry, DAPI (4′,6-diamidino-2-phenylindole dihydrochloride) staining, and a fluorescent probe were used, respectively. Our experiments revealed that mobile phone RFR did not cause DNA damage in marginal cells, and the rate of cell apoptosis did not increase (P > 0.05). However, the production of ROS in the 4 W/kg exposure group was greater than that in the control group (P < 0.05). In conclusion, these results suggest that mobile phone energy was insufficient to cause cell DNA damage and cell apoptosis following short-term exposure, but the cumulative effect of mobile phone radiation still requires further confirmation. Activation of the ROS system plays a significant role in the biological effects of RFR. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc. 相似文献