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- Blundred, Rachel, et al.
(författare)
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Human RECQL5 overcomes thymidine-induced replication stress.
- 2010
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7864 .- 1568-7856. ; 9:9, s. 964-75
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Tidskriftsartikel (refereegranskat)abstract
- Accurate DNA replication is essential to genome integrity and is controlled by five human RecQ helicases, of which at least three prevent cancer and ageing. Here, we have studied the role of RECQL5, which is the least characterised of the five human RecQ helicases. We demonstrate that overexpressed RECQL5 promotes survival during thymidine-induced slowing of replication forks in human cells. The RECQL5 protein relocates specifically to stalled replication forks and suppresses thymidine-induced RPA foci, CHK1 signalling, homologous recombination and gammaH2AX activation. It is unlikely that RECQL5 promotes survival through translesion synthesis as PCNA ubiquitylation is also reduced. Interestingly, we also found that overexpressing RECQL5 relieves cells of the cell cycle arrest normally imposed by thymidine, but without causing mutations. In conclusion, we propose that RECQL5 stabilises the replication fork allowing replication to overcome the effects of thymidine and complete the cell cycle.
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- Coleman, M P, et al.
(författare)
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Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership) : an analysis of population-based cancer registry data
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9760, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. METHODS: Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6% at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. FUNDING: Department of Health, England; and Cancer Research UK.
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- Jones, Timothy D., et al.
(författare)
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Diatom-inferred late Pleistocene and Holocene palaeolimnological changes in the Ioannina basin, northwest Greece
- 2013
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Ingår i: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 49:2, s. 185-204
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Tidskriftsartikel (refereegranskat)abstract
- The character and impact of climate change since the last glacial maximum (LGM) in the eastern Mediterranean region remain poorly understood. Here, two new diatom records from the Ioannina basin in northwest Greece are presented alongside a pre-existing record and used to infer past changes in lake level, a proxy for the balance between precipitation and evaporation. Comparison of the three records indicates that lake-level fluctuations were the dominant driver of diatom assemblage composition change, whereas productivity variations had a secondary role. The reconstruction indicates low lake levels during the LGM. Late glacial lake deepening was underway by 15.0 cal kyr BP, implying that the climate was becoming wetter. During the Younger Dryas stadial, a lake-level decline is recorded, indicating arid climatic conditions. Lake Ioannina deepened rapidly in the early Holocene, but long-term lake-level decline commenced around 7.0 cal kyr BP. The pattern of lake-level change is broadly consistent with an existing lake-level reconstruction at Lake Xinias, central Greece. The timing of the apparent change, however, is different, with delayed early Holocene deepening at Xinias. This offset is attributed to uncertainties in the age models, and the position of Xinias in the rain shadow of the Pindus Mountains.
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