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排序方式: 共有3514条查询结果,搜索用时 146 毫秒
1.
Sharat J. Vayttaden Jacqueline Friedman Tuan M. Tran Thomas C. Rich Carmen W. Dessauer Richard B. Clark 《PLoS computational biology》2010,6(1)
We developed a unified model of the GRK-mediated β2 adrenergic receptor (β2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the β2AR; (3) β2AR internalization; (4) recycling of the β2AR post isoproterenol treatment; (5) β2AR desensitization; and (6) β2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict the consequences of (1) modifying rates such as GRK phosphorylation of the receptor, arrestin binding and dissociation from the receptor, and receptor dephosphorylation that should reflect effects of knockdowns and overexpressions of these components; and (2) varying concentration and frequency of agonist stimulation “seen” by the β2AR to better mimic hormonal, neurophysiological and pharmacological stimulations of the β2AR. Exploring the consequences of rapid pulsatile agonist stimulation, we found that although resensitization was rapid, the β2AR system retained the memory of the previous stimuli and desensitized faster and much more strongly in response to subsequent stimuli. The latent memory that we predict is due to slower membrane dephosphorylation, which allows for progressive accumulation of phosphorylated receptor on the surface. This primes the receptor for faster arrestin binding on subsequent agonist activation leading to a greater extent of desensitization. In summary, the model is unique in accounting for the behavior of the β2AR system across multiple types of biochemical measurements using a single set of experimentally constrained parameters. It also provides insight into how the signaling machinery can retain memory of prior stimulation long after near complete resensitization has been achieved. 相似文献
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J Bézard B Vigier D Tran P Mauléon N Josso 《Journal of reproduction and fertility》1987,80(2):509-516
Anti-Müllerian hormone (AMH) was detected in perinatal and postnatal sheep ovaries, using avidin-biotin immunohistochemistry with a monoclonal antibody specific for ruminant AMH. Immunoreactivity was limited to granulosa cells, and was influenced both by the degree of follicular development, and by the age of the animal. In the fetus, only the most advanced follicles exhibited a faint immunoreactivity at 120 days gestation, and no reaction was observed in younger animals. Immediately before and after birth, primordial follicles were still negative, but a faint reaction was elicited in young growing follicles, increasing with follicle size. Strong immunoreactivity was visible in antral follicles, especially in the innermost granulosa cell layers, close to the oocyte and lining the antral cavity. 相似文献
5.
Tumor necrosis factor induces acute phase proteins in rats 总被引:2,自引:0,他引:2
I Gresser F Delers N Tran Quangs S Marion R Engler C Maury C Soria J Soria W Fiers J Tavernier 《Journal of biological regulators and homeostatic agents》1987,1(4):173-176
Inoculation of WAG rats with recombinant mouse tumor necrosis factor results in a rapid and marked increase in several acute phase proteins in the serum (haptoglobin, alpha 1 acid glycoprotein, alpha 2 macroglobulin) and in the plasma (fibrinogen). We conclude that TNF may play an important role in the inflammatory response in vivo and possibly in the pathogenesis of inflammatory disorders. 相似文献
6.
Purified bovine AMH induces a characteristic freemartin effect in fetal rat prospective ovaries exposed to it in vitro 总被引:5,自引:0,他引:5
To determine whether anti-Müllerian hormone (AMH) is responsible for the gonadal lesions observed in bovine genetic females united by placental anastomoses to male twins (freemartins), prospective ovaries of fetal rats were exposed to purified bovine AMH in vitro. In cultures initiated at 14 days p.c. and maintained 3 to 10 days, AMH consistently induced a characteristic 'freemartin effect', namely reduction of gonadal volume, germ cell depletion and differentiation, in the gonadal blastema, of epithelial cells with large clear cytoplasm linked by interdigitations, resembling rat fetal Sertoli cells. These cells tend to become polarized and form cords, delineated by a continuous basal membrane containing laminin and fibronectin. Such structures, resembling developing seminiferous cords, were not detected in control ovarian cultures. These data strongly suggest that AMH is the testicular factor responsible for triggering the morphological abnormalities of freemartin gonads. 相似文献
7.
Neuronal gene expression in aluminum myelopathy 总被引:3,自引:0,他引:3
Parhad Irma M. Krekoski Craig A. Mathew Anil Tran Phu M. 《Cellular and molecular neurobiology》1989,9(1):123-138
1. Aluminum administration to susceptible animal species results in neurofilament accumulation in neuronal perikarya and proximal axons. Pathogenetic studies in vivo have shown that aluminum rapidly associates with neuronal chromatin. Whether the effect of aluminum on DNA components plays a role in the production of the neurofibrillary lesion remains unclear. 2. In this study we used Northern analysis and in situ hybridization to evaluate mRNA levels of specific neuronal and glial components in the rabbit spinal cord at various times following aluminum administration. 3. Our results show that (a) all neuronal mRNAs evaluated (neurofilament triplet components, neuronal-specific enolase, and amyloid precursor protein) are markedly decreased, with no decrease in glial fibrillary acidic protein; (b) the effect on neuronal gene expression occurs early and concurrently with the development of the neurofibrillary lesion and reverses rapidly after a single dose of aluminum; and (c) there is a direct correlation between the severity of the neurofibrillary lesion and the decrease in neuronal mRNA levels. 4. We interpret our results to mean that the accumulation of neurofilaments in this model is not due to a selective effect on neurofilament gene expression but may be due to an inhibition of genes coding for components involved in processing of neurofilament proteins. 相似文献
8.
Ghan Shyam Lohiya Hubert Pirkle Hoan Nguyen Sunita Lohiya Tran Vuu 《The Western journal of medicine》1988,148(4):426-429
We reviewed records of all persons dying between 1979 and 1986 in eight California institutions for the mentally retarded. Autopsies had been done in 71% of the 1,181 deaths. Nine deaths were due to hepatocellular carcinoma, which invariably developed in carriers of hepatitis B surface antigen (HBsAg) and was fatal within four months of diagnosis. The mean age at death was 32.7 years. The incidence of hepatocellular carcinoma in HBsAg carriers was 140 times greater than in the US population. Persistent hepatitis B infection was probably etiologically related to hepatocellular carcinoma in this population, which is relatively free of exposure to other hepatocarcinogens. 相似文献
9.
A V79 Chinese hamster cell line XR-V15B exhibiting hypersensitivity to X-ray has been isolated and characterized. Additionally to increased X-ray-sensitivity (approximately 8-fold, as judged by D10 values), cross-sensitivity to bleomycin (3-fold increase), 4NQO (3-fold), H2O2, EMS, MMS (2-fold) were observed also. No increased sensitivity to UV and MMC was found. Genetic complementation analysis indicates that XR-V15B belongs to the same complementation group as the X-ray-sensitive (xrs) mutants of Chinese hamster ovary (CHO) cells described by Jeggo (1985). Biochemical analysis of XR-V15B confirms this finding: the mutant showed a decreased ability to rejoin double-strand breaks induced by X-ray as measured by neutral elution. After 4 h of repair more than 50% of the double-strand breaks remain in comparison to 3% in V79 cells. No difference was observed between wild-type and XR-V15B cells in the initial number of single-strand breaks induced, in the kinetics of their rejoining and in the final level of unrejoined single-strand breaks. Treatment with 5-azacytidine did not have an effect on the reversion frequency of XR-V15B, contrary to the results obtained with the xrs mutants. XR-V15B has been grown in continuous culture for more than 3 months without evidence of reversion. The mutation induction by X-ray irradiation at the HPRT locus is not significantly increased in the mutant, but at doses giving the same degree of cell killing, XR-V15B cells are hypomutable. 相似文献
10.
Wolfson M. R.; Tran N.; Bhutani V. K.; Shaffer T. H. 《Journal of applied physiology》1988,65(3):1436-1443
In this report, an experimental approach and newly designed apparatus for liquid ventilation of preterm animals are described. Findings of age-related changes in cardiopulmonary function of this animal preparation are presented. Thirty-one lambs, 102-137 days gestation (term 147 +/- 3 days), were studied. The carotid artery, jugular vein, and trachea of the exteriorized fetus were cannulated under local anesthesia. Immediately after cesarean section delivery, ventilation commenced; warmed (39 degrees C) and oxygenated (PIO2 greater than 500 Torr) liquid fluorocarbon (RIMAR 101) was delivered to the lung by a mechanically assisted liquid ventilation system. Skeletal muscle paralysis, low-dose exogenous buffering, and thermal support were maintained during the 3-h experiment. Pulmonary gas exchange, acid-base status, and cardiopulmonary and metabolic function were assessed. By utilizing these techniques, effective arterial oxygenation, CO2 elimination, acid-base status, and cardiovascular stability were supported independent of gestational age. The results demonstrate a developmental increase in specific lung compliance and mean arterial pressure and decrease in heart rate and systemic O2 consumption per kilogram with advancing gestational age. These findings demonstrate that liquid ventilation negates the dependency of effective pulmonary gas exchange on surfactant development, thereby extending the limits of viability of the immature extrauterine lamb. As such this new experimental approach is useful for the study of physiological development over an age range previously limited to fetal animal preparations and, therefore, may provide insight regarding adaptation of the premature to the extrauterine environment. 相似文献