1000 resultados para 02081510 CTD-23


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2010

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2010

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Winter, Rudolf; Jones, A.R.; Greaves, G.N.; Smith, I.H., (2005) 'Na-23, Si-29, and C-13 MAS NMR investigation of glass-forming reactions between Na2CO3 and SiO2', Journal of Physical Chemistry B 109(49) pp.23154-23161 RAE2008

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Winter, Rudolf; Jones, A.R.; Florian, P.; Massiot, D., (2005) 'Tracing the reactive melting of glass-forming silicate batches by in situ Na-23 NMR', Journal of Physical Chemistry B 109(10) pp.4324-4332 RAE2008

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BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1. These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1) to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, NUP188, POM34) and cytoplasmic mRNA decay at P-bodies (CCR4, DHH1). Strikingly, BRCA1 interacted with the phosphorylated RNA polymerase II (RNAPII) carboxy terminal domain (P-CTD), phosphorylated in the pattern specified by the CTDK-I kinase, to induce DEF1-dependent cleavage and accumulation of a RNAPII fragment containing the P-CTD. Significantly, breast cancer associated BRCT domain defects in BRCA1 that suppressed P-CTD cleavage and lethality in yeast also suppressed the physical interaction of BRCA1 with human SPT5 in breast epithelial cells, thus confirming SPT5 as a relevant target of BRCA1 interaction. Furthermore, enhanced P-CTD cleavage was observed in both yeast and human breast cells following UV-irradiation indicating a conserved eukaryotic damage response. Moreover, P-CTD cleavage in breast epithelial cells was BRCA1-dependent since damage-induced P-CTD cleavage was only observed in the mutant BRCA1 cell line HCC1937 following ectopic expression of wild type BRCA1. Finally, BRCA1, SPT5 and hyperphosphorylated RPB1 form a complex that was rapidly degraded following MMS treatment in wild type but not BRCA1 mutant breast cells. These results extend the mechanistic links between BRCA1 and transcriptional consequences in response to DNA damage and suggest an important role for RNAPII P-CTD cleavage in BRCA1-mediated cancer suppression.

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Scholarly consensus holds that a law quoted in Demosthenes (23.53) permitted one to kill a highway robber who had lain in ambush and attacked one on a road. But the relevant phrase says nothing explicit about ambush. Modern interpretation derives from Harpocration and other ancient authorities. It is argued here that they were mistaken and that the phrase referred to those who inadvertently killed a fellow traveler while overtaking on a road.' The new interpretation may offer another way to think about the encounter between Oedipus and Laius.

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This memoir recalls the instruments in the Electron Microscope Unit and the staff, students and visitors who used them. Accessory equipment is also described because much of it was innovative and built in the laboratory, also, much of the science would not have been possible without it. This publication includes 33 figures, 4 plates and 7 appendices. The appendices record that 54 MBA staff and 196 students and visitors have used the microscopes and that 413 titles have been published (to the end of 2006).