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111.
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Proximity of two tryptophan residues in dihydrofolate reductase determined by 19f NMR 总被引:1,自引:0,他引:1
B J Kimber J Feeney G C Roberts B Birdsall D V Griffiths A S Burgen B D Sykes 《Nature》1978,271(5641):184-185
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Zusammenfassung Hypophysenlose Ratten zeigten nach Injektion von 1-Aminocyclopentancarboxylsäure (NSC-1026) keine pathologischen Symptome, wie normale mit dieser Substanz behandelte Tiere. Vergleichsversuche mit Reserpin-vorbehandelten Ratten, nachbehandelt mit NSC-1026, erbrachten keine befriedigenden Resultate. 相似文献
116.
Translocation of conjugative transposons proceeds via excision of the element to generate a circular molecule that can then
integrate into a new site, which can be in the same or a different cell. This review summarises some of the different mechanisms
used for excision and integration of conjugative transposons.
RID="*"
ID="*"Corresponding author. 相似文献
117.
Products of the isoprostane pathway: unique bioactive compounds and markers of lipid peroxidation 总被引:16,自引:0,他引:16
We previously reported the discovery of prostaglandin F2-like compounds (F2-isoprostanes) formed by nonenzymatic free-radical-induced peroxidation of arachidonic acid. Quantification of F2-isoprostanes has proven to be a major advance in assessing oxidative stress status in vivo. Central in the pathway of formation of isoprostanes are prostaglandin H2-like endoperoxides, which also undergo rearrangement in vivo to form E-ring, D-ring, and thromboxane-ring compounds. E2- and D2-isoprostanes also undergo dehydration in vivo to form reactive cyclopentenone A2- and J2-isoprostanes, which are susceptible to Michael addition reactions with thiols. Recently, we described the formation of highly reactive gamma-ketoaldehydes (now termed isoketals) as products of isoprostane endoperoxide rearrangement which readily adduct to lysine residues on proteins and induce cross-links at rates that far exceed other aldehyde products of lipid peroxidation. Isoprostane-like compounds (neuroprostanes) and isoketal-like compounds (neuroketals) are formed from oxidation of docosahexaenoic acid, which is enriched in the brain, and measurement of neuroprostanes may provide a unique marker of oxidative neuronal injury. 相似文献
118.
Kielman MF Rindapää M Gaspar C van Poppel N Breukel C van Leeuwen S Taketo MM Roberts S Smits R Fodde R 《Nature genetics》2002,32(4):594-605
The Wnt signal-transduction pathway induces the nuclear translocation of membrane-bound beta-catenin (Catnb) and has a key role in cell-fate determination. Tight somatic regulation of this signal is essential, as uncontrolled nuclear accumulation of beta-catenin can cause developmental defects and tumorigenesis in the adult organism. The adenomatous polyposis coli gene (APC) is a major controller of the Wnt pathway and is essential to prevent tumorigenesis in a variety of tissues and organs. Here, we have investigated the effect of different mutations in Apc on the differentiation potential of mouse embryonic stem (ES) cells. We provide genetic and molecular evidence that the ability and sensitivity of ES cells to differentiate into the three germ layers is inhibited by increased doses of beta-catenin by specific Apc mutations. These range from a severe differentiation blockade in Apc alleles completely deficient in beta-catenin regulation to more specific neuroectodermal, dorsal mesodermal and endodermal defects in more hypomorphic alleles. Accordingly, a targeted oncogenic mutation in Catnb also affects the differentiation potential of ES cells. Expression profiling of wildtype and Apc-mutated teratomas supports the differentiation defects at the molecular level and pinpoints a large number of downstream structural and regulating genes. Chimeric experiments showed that this effect is cell-autonomous. Our results imply that constitutive activation of the Apc/beta-catenin signaling pathway results in differentiation defects in tissue homeostasis, and possibly underlies tumorigenesis in the colon and other self-renewing tissues. 相似文献
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Gene expression profiling predicts clinical outcome of breast cancer 总被引:243,自引:0,他引:243
van 't Veer LJ Dai H van de Vijver MJ He YD Hart AA Mao M Peterse HL van der Kooy K Marton MJ Witteveen AT Schreiber GJ Kerkhoven RM Roberts C Linsley PS Bernards R Friend SH 《Nature》2002,415(6871):530-536
Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy. 相似文献
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