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991.
G S Jimenez F Bryntesson M I Torres-Arzayus A Priestley M Beeche S Saito K Sakaguchi E Appella P A Jeggo G E Taccioli G M Wahl M Hubank 《Nature》1999,400(6739):81-83
Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage. 相似文献
992.
993.
994.
Temporal trends of perfluoroalkyl substances (PFASs) have been determined in the blood samples from several countries globally including a female population in Sweden recently, yet little is known about the time trends in the blood levels of these compounds in Swedish male populations over recent years. In this study, the fourteen target PFASs consisted of four perfluorosulfonates (PFSAs) and ten perfluorocarboxylates (PFCAs) in the whole blood samples, collected from 153 Swedish elderly men during the period between 2008 and 2010, were analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). As the dominant PFASs contaminants in the blood samples, perfluorooctane sulfo- nate (PFOS) showed the highest geometric mean (GM) at 8.5 ng/mL, ranging from 1.7 to 29 ng/mL, while blood perfluorooctanoic acid (PFOA) contained the GM of 1.8 ng/mL, ranging from 0.35 to 6.4 ng/mL. Both the levels of these two compounds were lower than those determined in the blood samples of Swedish elderly pop- ulations derived from the late 1990s. According to the temporal trend analysis, over the three years, the blood levels of PFOS in Swedish male populations declined 16 % per annum, while those of perfluoroundecanoic acid (PFUnDA) increased 6.1% per annum, which were con- sistent with those reported previously for the populations from other countries. 相似文献
995.
In the process of ferromagnetic thermoseeds mediated magnetic induction hyperthermia, the tempera- ture distribution in the tumor region is a key factor to determine the therapy effect. During the preoperative treatment planning, discrepancies of the treatment parameters may lead to the temperature distribution uncertainty within the target area. Inaccurate prediction of temperature distribution may induce the treatment failure; therefore, it would be significant to investigate the uncertainty of tissue temperature prediction caused by the disturbance of calculation parameters. In this paper, 3D temperature field and necrosis zone of tissues in ferromagnetic thermoseeds hyperthermia are simulated by the finite volume algorithm, and effects of parameter uncertainties on the temperature distribution are revealed. Results show that selecting appropriate magnetic field parameters for treatment is a priority to guarantee therapeutic effect. Thermoseed properties and blood perfusion rate are the obvious disturbing terms for temperature distribution, while the metabolic heat of bio-tissues can often be ignored within limits. Our investigation is of importance for guiding reasonable and optimal preoperative treatment planning. 相似文献
996.
997.
Death of mature T cells by separate ligation of CD4 and the T-cell receptor for antigen 总被引:48,自引:0,他引:48
Effector T cells are restricted to recognizing antigens associated with major histocompatibility complex (MHC) molecules. Specific recognition is mediated by the alpha beta heterodimer of the T-cell receptor (TCR)/CD3 complex, although other membrane components are involved in T-cell antigen recognition and functions. There has been much controversy in this regard over the part played by the CD4 glycoprotein. It is known that expression of CD4 correlates closely with the cell's ability to recognize antigens bound to class II MHC molecules and that CD4 can bind to class II molecules. Also monoclonal antibodies to CD4 can modify signals generated through the TCR/CD3 complex. It has therefore been proposed that CD4 binds to class II molecules, coaggregates with the TCR-CD3 complex and aids the activation of T cells. But given that TCR can itself impart restriction on the cell, it remains unclear whether the contribution of CD4-derived signals to those generated through the TCR alpha beta-CD3 complex is central to this activation. Here we report that when preceded by ligation of CD4, signalling through TCR alpha beta results in T cell unresponsiveness due to the induction of activation dependent cell death by apoptosis. These results imply that CD4 is critically involved in determining the outcome of signals generated through TCR, and could explain why the induction of effector T cells needs to be MHC-restricted. 相似文献
998.
The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine. The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin. 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase. 相似文献
999.
以海带和番茄为原料通过科学调配,研制而成天然碘复合饮料。其工艺特点是将海带通过一系列加工程序,在保持其天然营养的前提下加工成汁,然后与番茄汁、菠萝汁及其它辅料按其营养成分进行科学合理的调配,从而制成每瓶含碘80~90μg的天然补碘饮料,该饮料具有营养补碘之功效,又具有色、香、味俱佳的特点。 相似文献
1000.
浅析电算化会计信息系统的内部控制制度 总被引:1,自引:0,他引:1
Zhai Youkang 《科学之友》2007,(11)
文章分析了会计电算化对内部控制的影响,并以此为基础探讨关于电算化会计信息系统环境下的内部控制建设问题,以确保企业实行会计电算化后,系统能够正常、安全、有效地运行。 相似文献