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911.
Camille Saini André Liani Thomas Curie Pascal Gos Florian Kreppel Yann Emmenegger Luigi Bonacina Jean-Pierre Wolf Yves-Alain Poget Paul Franken Ueli Schibler 《Genes & development》2013,27(13):1526-1536
The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase. 相似文献
912.
C. Van Bree N. A. P. Franken F. A. M. Snel J. Haveman P. J. M. Bakker 《International journal of hyperthermia》2013,29(4):337-346
The objective was to test the hypothesis that wild-type p53-function is required for the enhancement of the cytotoxicity of cis-diammine-dichloroplatinum(II) (cDDP) cytotoxicity by hyperthermia (HT). Human colorectal carcinoma cells (RKO) with wild-type p53-function and transfectants with HPV16-E6 or with a dominant negative mutant p53 were used. Cells were treated with HT (60min at 41°C, 43°C, 45°C: HT41, HT43, HT45), with various doses of cDDP alone or with a combined treatment, simultaneously applied. Survival was determined by clonogenic assays. Levels and localization of p53 were analysed with immunocytochemistry and Western blotting. The extent of HT41-enhanced cytotoxicity of cDDP was similar in all cell lines studied. Immunocytochemistry of wild-type p53 cells showed that p53 is transferred to the nucleus within 5h after HT43, whilst after HT41 no significant effects were observed. Cell fractionation experiments of wild-type p53 cells showed that, immediately after HT43/ HT45, nuclear p53-levels increased as compared to controls, but could not be extracted from the matrix. The extractability was restored 3-5h after treatment. No significant differences in p53-levels were observed after HT41. These results indicate that, although HT43/HT45 might shortly inactivate p53-function, probably by protein aggregation to the nuclear matrix, the HT-enhanced cDDP-cytotoxicity does not depend on p53-function. 相似文献