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p53 mutant mice that display early ageing-associated phenotypes. 总被引:56,自引:0,他引:56
Stuart D Tyner Sundaresan Venkatachalam Jene Choi Stephen Jones Nader Ghebranious Herbert Igelmann Xiongbin Lu Gabrielle Soron Benjamin Cooper Cory Brayton Sang Hee Park Timothy Thompson Gerard Karsenty Allan Bradley Lawrence A Donehower 《Nature》2002,415(6867):45-53
The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing. 相似文献
33.
5套 37℃的扰乱试验实施在 3台厌气完全混合反应器中。三反应器分别处理着以丙酸、丁酸和混合脂肪酸为基质的废水。扰乱由脉冲添加丙酸、丁酸或甲酸来建立。结果表示 ,扰乱立即导致了相应的酸和氢分压(pH2 )的浓度积累。但所有反应器能完全地恢复在 2 0 0h之内。混合液相中丙酸和丁酸的积累没有导致pH的重大变化。但是 ,PH2 的增加限制了丙酸和丁酸的转换 ;各自的阈值分别为 2 1× 10 - 4及 1 1× 10 - 3atm。异丁酸和二高分子羟基酸 ,valerate和caproate ,被检出存在于一些被扰乱的反应器流出水中。对于丁酸异构化pH2 的作用是非决定性的。实验数据的热力学分析表示 ,valerate和caproate的形成或归结于pH2 的增加或独立于pH2 的增加。在后者 ,形成直接地归结于混合液相中丙酸或丁酸的浓度增加。 相似文献
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Kerstin Buttler Muhammad Badar Virginia Seiffart Sandra Laggies Gerhard Gross Jörg Wilting Herbert A. Weich 《Cellular and molecular life sciences : CMLS》2014,71(8):1513-1527
Cellular pro-angiogenic therapies may be applicable for the treatment of peripheral vascular diseases. Interactions between mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) may provide such a treatment option. With the exception of some studies in man, experiments have only been performed in immunodeficient mice and rats. We studied an immunocompetent syngeneic mouse model. We isolated MSCs from bone marrow and EPCs from the lung of adult C57/Bl.6 mice and co-injected them in Matrigel subcutaneously in adult C57/Bl.6 mice. We demonstrate development of both blood vessels and lymphatics. Grafted EPCs integrated into the lining of the two vessel types, whereas MSCs usually did not incorporate into the vessel wall. Injections of each separate cell type did not, or hardly, reveal de novo angiogenesis. The release of VEGF-A by MSCs has been shown before, but its inhibitors, e.g., soluble VEGF receptors, have not been studied. We performed qualitative and quantitative studies of the proteins released by EPCs, MSCs, and cocultures of the cells. Despite the secretion of VEGF inhibitors (sVEGFR-1, sVEGFR-2) by EPCs, VEGF-A was secreted by MSCs at bioavailable amounts (350 pg/ml). We confirm the secretion of PlGF, FGF-1, MCP-1, and PDGFs by EPCs/MSCs and suggest functions for VEGF-B, amphiregulin, fractalkine, CXCL10, and CXCL16 during MSC-induced hem- and lymphangiogenesis. We assume that lymphangiogenesis is induced indirectly by growth factors from immigrating leukocytes, which we found in close association with the lymphatic networks. Inflammatory responses to the cellular markers GFP and cell-tracker red (CMPTX) used for tracing of EPCs or MSCs were not observed. Our studies demonstrate the feasibility of pro-angiogenic/lymphangiogenic therapies in immunocompetent animals and indicate new MSC/EPC-derived angiogenic factors. 相似文献
35.
The spindle assembly checkpoint guards against chromosomal missegregation but does not induce arrest in oocytes that contain a few achiasmatic chromosomes (univalents). We followed the fate of univalents in oocytes during the first meiotic division, and although these preserved a meiotic kinetochore structure, they were also bi-oriented in a mitotic manner. The hybrid chromosomal configuration attained by univalents allows them to evade the spindle assembly checkpoint and contribute to aneuploidy in oocytes. 相似文献
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Cloning and sequence analysis of cDNA for bovine carboxypeptidase E 总被引:10,自引:0,他引:10
Carboxypeptidase E (enkephalin convertase) was first identified as the carboxypeptidase B-like enzyme involved in the biosynthesis of enkephalin in bovine adrenal chromaffin granules. A similar enzyme is present in many brain regions and in purified secretory granules from rat pituitary and rat insulinoma. Within the secretory granules, carboxypeptidase E (CPE) activity is found in both a soluble and a membrane-bound form, which differ slightly in relative molecular mass (Mr). Here, to investigate whether the CPE activities in the various tissues are produced from a single gene, purified CPE was partially sequenced and oligonucleotide probes were used to isolate a clone encoding CPE from a bovine pituitary complementary DNA library. This cDNA hybridizes to bovine pituitary poly(A)+ RNAs of approximately 3.3, 2.6 and 2.1 kilobases (kb), with the 3.3-kb messenger RNA the predominant species. The predicted amino-acid sequence of the cDNA clone contains the partially determined sequences of CPE, several pairs of basic amino acids and displays some homology with both carboxypeptidases A and B. Restriction analysis of bovine genomic DNA suggests only one gene for CPE. This is consistent with a broad role for CPE in the biosynthesis of many neuropeptides. 相似文献
38.
Biosynthesis and processing of cellular and viral polyproteins 总被引:1,自引:0,他引:1
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