排序方式: 共有74条查询结果,搜索用时 31 毫秒
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Bevilacqua V Chiarappa P Mastronardi G Menolascina F Paradiso A Tommasi S 《基因组蛋白质组与生物信息学报(英文版)》2008,6(2):91-97
In considering key events of genomic disorders in the development and progression of cancer, the correlation between genomic instability and carcinogenesis is currently under investigation. In this work, we propose an inductive logic programming approach to the problem of modeling evolution patterns for breast cancer. Using this approach, it is possible to extract fingerprints of stages of the disease that can be used in order to develop and deliver the most adequate therapies to patients. Furthermore, such a model can help physicians and biologists in the elucidation of molecular dynamics underlying the aberrations-waterfall model behind carcinogenesis. By showing results obtained some hints about further approach to the hypotheses. on a real-world dataset, we try to give knowledge-driven validations of such 相似文献
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Yu WH Karanth S Mastronardi CA Sealfon S Dean C Dees WL McCann SM 《Experimental biology and medicine (Maywood, N.J.)》2002,227(9):786-793
Lamprey gonadotropin-releasing hormone-III (l-GnRH-III), the putative follicle-stimulating hormone (FSH)-releasing factor (FSHRF), exerts a preferential FSH-releasing activity in rats both in vitro and in vivo. To test the hypothesis that l-GnRH-III acts on its own receptors to stimulate gonadotropin release, the functional activity of this peptide at mammalian (m) leutinizing hormone (LH)RH receptors transfected to COS cells was tested. l-GnRH-III activated m-LHRH receptors only at a minimal effective concentration (MEC) of 10(-6) M, whereas m-LHRH was active at a MEC of 10(-9) M, at least 1,000 times less than that required for l-GnRH-III. In 4-day monolayer cultured cells, l-GnRH-III was similarly extremely weak in releasing either LH or FSH, and, in fact, it released LH at a lower concentration (10(-7) M) than that required for FSH release (10(-6) M). In this assay, m-LHRH released both FSH and LH significantly at the lowest concentration tested (10(-10) M). On the other hand, l-GnRH-III had a high potency to selectively release FSH and not LH from hemipituitaries of male rats. The results suggest that the cultured cells were devoid of FSHRF receptors, thereby resulting in a pattern of FSH and LH release caused by the LHRH receptor. On the other hand, the putative FSH-releasing factor receptor accounts for the selective FSH release by l-GnRH-III when tested on hemipituitaries. Removal of calcium from the medium plus the addition of EGTA, a calcium chelator, suppressed the release of gonadotropins induced by either l-GnRH-III or LHRH, indicating that calcium is required for the action of either peptide. Previous results showed that sodium nitroprusside, a releaser of nitric oxide (NO), causes the release of both FSH and LH from hemipituitaries incubated in vitro. In the present experiments, a competitive inhibitor of NO synthase, L-NG-monomethyl-L-arginine (300 micro M) blocked the action of l-GnRH-III or partially purified FSHRF. The results indicate that l-GnRH-III and FSHRF act on putative FSHRF receptors by a calcium-dependent NO pathway. 相似文献
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Mastronardi CA Walczewska A Yu WH Karanth S Parlow AF McCann SM 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》2000,224(3):152-158
In humans there is a circadian rhythm of leptin concentrations in plasma with a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we determined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h. To determine if this rhythm is controlled by nocturnally released hormones, we evaluated the effect of hormones known to be released at night in humans, some of which are also known to be released at night in rats. In humans, prolactin (PRL), growth hormone (GH), and melatonin are known to be released at night, and adrenocorticotropic hormone (ACTH) release is inhibited. In these experiments, conscious rats were injected intravenously with 0.5 ml diluent or the substance to be evaluated just after removal of the first blood sample (0.3 ml), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 microg) produced a rapid increase in plasma leptin that persisted for the duration of the experiment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, alpha bromoergocryptine (1.5 mg), a dopamine-2-receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the decline persisted for 120 min. The minimal effective dose of GH to lower plasma leptin was 1 mg/rat. Insulin-like growth factor (IGF-1) (10 microg), but not IGF-2 (10 microg), also significantly decreased plasma leptin. Melatonin, known to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter leptin release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0. 1-mg dose but produced a delayed, significant increase in leptin, manifest 100-120 min after injection of a 1 mg dose. Since glucocorticoids decrease at night in humans at the time of the maximum plasma concentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of corticosterone following stress in the rat and that glucocorticoids are not responsible for the circadian rhythm of leptin concentration. Therefore, we conclude that an increase in PRL secretion during the night may be responsible, at least in part, for the nocturnal elevation of leptin concentrations observed in rats and humans. 相似文献
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Sarver RW Peevers J Cody WL Ciske FL Dyer J Emerson SD Hagadorn JC Holsworth DD Jalaie M Kaufman M Mastronardi M McConnell P Powell NA Quin J Van Huis CA Zhang E Mochalkin I 《Analytical biochemistry》2007,360(1):30-40
Renin is an aspartyl protease involved in the production of angiotensin II, a potent vasoconstrictor. Renin inhibitors can prevent blood vessel constriction and therefore could be useful for the treatment of hypertension. High-throughput screening efforts identified a small molecule renin inhibitor with a core substituted diaminopyrimidine ring. Parallel medicinal chemistry efforts based on this lead resulted in compound 1. A complex of 1 bound to renin was crystallized, and structural data were obtained by X-ray diffraction. The structure indicated that there were adjacent unoccupied binding pockets. Synthetic efforts were initiated to extend functionality into these pockets so as to improve affinity and adjust pharmacokinetic parameters. Thermodynamics data for inhibitor binding to renin were also collected using isothermal titration calorimetry. These data were used to help guide inhibitor optimization by suggesting molecular alterations to improve binding affinity from both thermodynamic and structural perspectives. The addition of a methoxypropyl group extending into the S3 subpocket improved inhibitor affinity and resulted in greater binding enthalpy. Initial additions to the pyrimidine ring template that extended into the large hydrophobic S2 pocket did not improve affinity and dramatically altered the thermodynamic driving force for the binding interaction. Binding of the core template was enthalpically driven, whereas binding of initial inhibitors with S2 extensions was both enthalpically and entropically driven but lost significant binding enthalpy. Additional electrostatic interactions were then incorporated into the S2 extension to improve binding enthalpy while taking advantage of the favorable entropy. 相似文献
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Cross validation (CV) was used to analyze the effects of different environments and different genotypic samples on estimates of the proportion of genotypic variance explained by QTL (p). Testcrosses of 344 F(3) maize lines grown in four environments were evaluated for a number of agronomic traits. In each of 200 replicated CV runs, this data set was subdivided into an estimation set (ES) and various test sets (TS). ES were used to map QTL and estimate p for each run (p(ES)) and its median (p(ES)) across all runs. The bias of these estimates was assessed by comparison with the median (p(TS.ES)) obtained from TS. We also used two independent validation samples derived from the same cross for further comparison. The median p(ES) showed a large upward bias compared to p(TS.ES). Environmental sampling generally had a smaller effect on the bias of p(ES) than genotypic sampling or both factors simultaneously. In independent validation, p(TS.ES) was on average only 50% of p(ES). A wide range among p(ES) reflected a large sampling error of these estimates. QTL frequency distributions and comparison of estimated QTL effects indicated a low precision of QTL localization and an upward bias in the absolute values of estimated QTL effects from ES. CV with data from three QTL studies reported in the literature yielded similar results as those obtained with maize testcrosses. We therefore recommend CV for obtaining asymptotically unbiased estimates of p and consequently a realistic assessment of the prospects of MAS. 相似文献
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Mostefai HA Agouni A Carusio N Mastronardi ML Heymes C Henrion D Andriantsitohaina R Martinez MC 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):5028-5035
Microparticles (MPs) are membrane vesicles released during cell activation and apoptosis. We have previously shown that MPs from apoptotic T cells induce endothelial dysfunction, but the mechanisms implicated are not completely elucidated. In this study, we dissect the pathways involved in endothelial cells with respect to both NO and reactive oxygen species (ROS). Incubation of endothelial cells with MPs decreased NO production that was associated with overexpression and phosphorylation of endothelial NO synthase (eNOS). Also, MPs enhanced expression of caveolin-1 and decreased its phosphorylation. Microparticles enhanced ROS by a mechanism sensitive to xanthine oxidase and P-IkappaBalpha inhibitors. PI3K inhibition reduced the effects of MPs on eNOS, but not on caveolin-1, whereas it enhanced the effects of MPs on ROS production. Microparticles stimulated ERK1/2 phosphorylation via a PI3K-depedent mechanism. Inhibition of MEK reversed eNOS phosphorylation but had no effect on ROS production induced by MPs. In vivo injection of MPs in mice impaired endothelial function. In summary, MPs activate pathways related to NO and ROS productions through PI3K, xanthine oxidase, and NF-kappaB pathways. These data underscore the pleiotropic effects of MPs on NO and ROS, leading to an increase oxidative stress that may account for the deleterious effects of MPs on endothelial function. 相似文献
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