From the water-insoluble lipid fraction of the methylene chloride/methanol extract of the starfish Cosmasterias lurida, two new glucosylceramides together with a known glucosylceramide, ophidiacerebroside E, were isolated by chromatographic
procedures and characterized by spectroscopic (1H and 13C nuclear magnetic resonance, mass spectrometry) methods. The new compounds were identified as (2S, 3R, 4E, 8E, 10E)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxyheptadecanoyl)amino]-9-methyl-4,8,10-octadecatriene (3) and (2S,3R,4E,8E,10E)-1-(β-d-glucopyranosyloxy)-3-hydroxy-2-[(R)-2-hydroxyoctadecanoyl)amino]-9-methyl-4,8,10-octadecatriene (4). 相似文献
Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients’ muscles. Finally, the administration of tideglusib and VP0.7, ATP non-competitive inhibitors of glycogen synthase kinase 3β (GSK-3β), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options. 相似文献
This study was designed to investigate if the kappa opioid system regulates the locomotor response to cocaine in the female rat and to determine if the effect is dependent on estradiol treatment. Adult rats were ovariectomized (OVX) and half received an estradiol (OVX-EB) implant. After a week, rats were injected for 5 consecutive days with vehicle or with the kappa opioid receptor (KOPr) agonist U-69593 (0.16, 0.32, and 0.64 mg/kg) 15 min prior to cocaine injection (15 mg/kg). Following a 7-day drug-free period, rats were challenged with cocaine (Day 13). The locomotor response to cocaine was measured on Days 1, 5, and 13. U-69593 (0.32 mg/kg) decreased cocaine-induced locomotor activity in drug-na?ve OVX rats and in those that received the OVX-EB implant. These results indicate that the acute effects of U-69593 are independent of estradiol treatment. Repeated exposure to U-69593 (0.32 mg/kg) prior to cocaine decreased the development of behavioral sensitization in OVX-EB-implanted rats. This decrease in cocaine-induced hyperlocomotion persisted after 1 week of cocaine withdrawal. These data indicate that the KOPr system participates in estradiol modulation of cocaine-induced behavioral sensitization in the female rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
It is already common to compute quantitative metrics of requirements to assess their quality. However, the risk is to build assessment methods and tools that are both arbitrary and rigid in the parameterization and combination of metrics. Specifically, we show that a linear combination of metrics is insufficient to adequately compute a global measure of quality. In this work, we propose to develop a flexible method to assess and improve the quality of requirements that can be adapted to different contexts, projects, organizations, and quality standards, with a high degree of automation. The domain experts contribute with an initial set of requirements that they have classified according to their quality, and we extract their quality metrics. We then use machine learning techniques to emulate the implicit expert’s quality function. We provide also a procedure to suggest improvements in bad requirements. We compare the obtained rule-based classifiers with different machine learning algorithms, obtaining measurements of effectiveness around 85%. We show as well the appearance of the generated rules and how to interpret them. The method is tailorable to different contexts, different styles to write requirements, and different demands in quality. The whole process of inferring and applying the quality rules adapted to each organization is highly automated.
Anthocyanins are among the most common flavonoids in the human diet. In spite of their very low bioavailability, anthocyanins are indicated as active in preventing the progress of cardiovascular and neurodegenerative diseases, obesity, inflammation, and cancer. Any piece of knowledge concerning absorption, tissue distribution, metabolism, and excretion of dietary anthocyanins is expected to help understanding the apparent paradox between their low concentrations in cells and their bioactivity. The aim of this work was to investigate the renal uptake of dietary anthocyanins and the underlying molecular mechanism. A solution containing anthocyanins extracted from grape (Vitis vinifera) was introduced into the isolated stomach of anesthetized rats; after both 10 and 30 min, plasma, liver, and kidney were analyzed for their anthocyanin contents. While anthocyanins in the liver were at apparent equilibrium with plasma both after 10 and 30 min, kidney anthocyanins were 3- and 2.3-fold higher than in plasma, after 10 and 30 min, respectively. Since the transport activity of the bilitranslocase in kidney basolateral membrane vesicles was competitively inhibited by malvidin 3-glucoside (K(i) = 4.8 +/- 0.2 microM), the anthocyanin uptake from blood into kidney tubular cells is likely to be mediated by the kidney isoform of this organic anion membrane transporter. 相似文献