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Recent studies have indicated the existence of tumorigenesis barriers that slow or inhibit the progression of preneoplastic lesions to neoplasia. One such barrier involves DNA replication stress, which leads to activation of the DNA damage checkpoint and thereby to apoptosis or cell cycle arrest, whereas a second barrier is mediated by oncogene-induced senescence. The relationship between these two barriers, if any, has not been elucidated. Here we show that oncogene-induced senescence is associated with signs of DNA replication stress, including prematurely terminated DNA replication forks and DNA double-strand breaks. Inhibiting the DNA double-strand break response kinase ataxia telangiectasia mutated (ATM) suppressed the induction of senescence and in a mouse model led to increased tumour size and invasiveness. Analysis of human precancerous lesions further indicated that DNA damage and senescence markers cosegregate closely. Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression.  相似文献   
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Okazaki R  Takaoka N  Nagao K  Sekiya M  Nakamura T 《Nature》2001,412(6849):795-798
Chondrules are silicate spherules that are found in abundance in the most primitive class of meteorites, the chondrites. Chondrules are believed to have formed by rapid cooling of silicate melt early in the history of the Solar System, and their properties should reflect the composition of (and physical conditions in) the solar nebula at the time when the Sun and planets were forming. It is usually believed that chondrules lost all their noble gases at the time of melting. Here we report the discovery of significant amounts of trapped noble gases in chondrules in the enstatite chondrite Yamato-791790, which consists of highly reduced minerals. The elemental ratios 36Ar/132Xe and 84Kr/132Xe are similar to those of 'subsolar' gas, which has the highest 36Ar/132Xe ratio after that of solar-type noble gases. The most plausible explanation for the high noble-gas concentration and the characteristic elemental ratios is that solar gases were implanted into the chondrule precursor material, followed by incomplete loss of the implanted gases through diffusion over time.  相似文献   
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建立了超高压电镜三维图像重构的方法与系统,首次在2MV加速电压下进行了从获得二维电镜像到三维重构尝试。通过图像校下在敢单轴放置试样夹中因试样高度变化引起的放大倍数和像转为动的问题;提出了利用投影像的镝像对称关系来确定倾斜轴方向以及计算倾斜角度上相邻两个投影像间的差来进行平移校直的方法,大肠杆菌试样重构的实验结果表明,超高压电镜三维图像重构技术能够有效地再现厚试样的内部构造,在生物学和材料科学等领域  相似文献   
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Structure and expression of a cloned cDNA for human interleukin-2   总被引:95,自引:0,他引:95  
A cDNA coding for human interleukin-2 (IL-2) has been cloned from a cDNA library prepared from partially purified IL-2 mRNA. The DNA sequence codes for a polypeptide which consists of 153 amino acids including a putative signal sequence. A biologically active polypeptide, characteristic of human IL-2, was produced when the cDNA was fused to a simian virus 40 promoter sequence and used to transfect cultured monkey COS cells.  相似文献   
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