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A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8-30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs. 相似文献
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Mamoru Fujiwara 《复旦学报(自然科学版)》2007,46(1):41-49
Recent developments of the synchroton radiation facilities and intense lasers are now guiding us to a new research frontier with probes of a high energy GeV photon beam and an intense and short pulse MeV γ-ray beam.We discuss new directions of the science developments with photo-nuclear reactions with the inverse Compton γ-rays for studying hadron structure, nuclear structure, astrophysics, materials science, as well as for nuclear technologies. 相似文献
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中亚热带南部与北部的亮叶水青冈林的比较研究--Ⅰ. 种组成、结构及更新 总被引:3,自引:0,他引:3
采用Braun-Blanquet,Fujiwara的植物社会学方法,对分布于中亚热带北部的八大公山及中亚热带南部的南山的亮叶水青冈林进行了植被生态学的比较研究,两个群落被区分.并比较了两群落的种组成、结构及生长更新的特征。 相似文献
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Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer 总被引:1,自引:0,他引:1
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The ultimate limit in the operation of an electronic device is the manipulation of a single charge. Such a limit has been achieved in single-electron tunnelling devices. However, these devices are based on multiple tunnel barriers and conductive islands, which are complex structures to fabricate. Here we demonstrate another type of device that can also manipulate elementary charge, but which is more suitable for large-scale integration. The device consists of two closely packed silicon wire-MOSFETs, which are commonly used building blocks of electronic circuits. We have developed a scheme to generate and store holes in the channels of either of these MOSFETs. Subsequently, holes can be transferred between the two MOSFETs at the level of an elementary charge, and their exact position can be monitored. This single-charge transfer device, which is operated at 25 K, is in effect a charge-coupled device. This is also the first realization of a silicon-based device that manipulates elementary charge. 相似文献
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Hitoshi Watarai Sayaka Wada Kazuhiko Fujiwara 《清华大学学报》2006,11(2):228-232
Introduction Optical activity is a fundamental property, which pro-vides valuable information on the structure of mole-cules and the conformation of their assemblies. There-fore, it is widely used in many fields including organic chemistry, coordination c… 相似文献
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Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression 总被引:2,自引:0,他引:2
Neumann CA Krause DS Carman CV Das S Dubey DP Abraham JL Bronson RT Fujiwara Y Orkin SH Van Etten RA 《Nature》2003,424(6948):561-565
Reactive oxygen species are involved in many cellular metabolic and signalling processes and are thought to have a role in disease, particularly in carcinogenesis and ageing. We have generated mice with targeted inactivation of Prdx1, a member of the peroxiredoxin family of antioxidant enzymes. Here we show that mice lacking Prdx1 are viable and fertile but have a shortened lifespan owing to the development beginning at about 9 months of severe haemolytic anaemia and several malignant cancers, both of which are also observed at increased frequency in heterozygotes. The haemolytic anaemia is characterized by an increase in erythrocyte reactive oxygen species, leading to protein oxidation, haemoglobin instability, Heinz body formation and decreased erythrocyte lifespan. The malignancies include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this protein functions as a tumour suppressor. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, whereas Prdx1-null mice have abnormalities in numbers, phenotype and function of natural killer cells. Our results implicate Prdx1 as an important defence against oxidants in ageing mice. 相似文献
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