TopBP1 contains transcriptional regulatory domains and regulates gene pathways involved in breast cancer

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Expression of TopBP1 in hereditary breast cancer

TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (p < 0.05). The level of TopBP1 mRNA appeared to be lower in poorly differentiated (III grade) hereditary breast cancer in comparison with moderately (II grade) and well-differentiated cancer (I grade) (p < 0.05 and p < 0.001 respectively). We analyzed TopBP1 protein expression using immunohistochemistry and Western blot techniques. Expression of TopBP1 protein was found to be significantly increased in poorly differentiated breast cancer (III grade) (p < 0.05). The percentage of samples with cytoplasmic apart from nuclear staining increased with increasing histological grade. There was no significant association between level and intracellular localization of TopBP1 protein in hereditary breast cancer and other clinicopathological parameters such as estrogen and progesterone receptors status, appearance of metastasis in the axillary lymph nodes and type of cancer. Our data suggest that decreased level of TopBP1 mRNA and increased level of TopBP1 protein might be associated with progression of hereditary breast cancer

Species pool versus site limitations of macrophytes in urban waters

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Climate versus in-lake processes as controls of the development of community structure in a low-arctic lake (South-West Greenland)

The dominant processes determining biological structure in lakes at millennial timescales are unclear. In this study, we used a multi-proxy approach to determine the relative importance of autogenic versus allogenic processes on the Holocene development of an oligotrophic lake in SW Greenland (66.99º N, 50.97º W). A 14C and 210Pb-dated sediment core covering ~8400 years BP was analysed for organic-inorganic carbon content, pigments, diatoms, chironomids, zooplankton and stable isotopes (13C, 18O). Relationships among the different proxies and a number of independent controlling variables (Holocene temperature, the 8.2 Kyr event, and immigration of Betula nana into the catchment) were explored using redundancy analysis (RDA) independent of time. The main ecological trajectories in the lake biota were captured by ordination first axis sample scores (18 – 32% variance explained). The importance of the arrival of Betula (ca. 6500 yBP) into the catchment was indicated by a series of partial-constrained ordinations, uniquely explaining ~15% of the variance in chironomids and ~9% in pigments. Climate influences on lake biota were strongest during the 8.2 Kyr cooling event, when all proxies responded rapidly although only chironomids had a unique component (in a partial-RDA) explained by the 8.2 Kyr event (8%). Holocene climate explained less variance than either catchment changes or biotic relationships. The sediment record at this site indicates the importance of catchment factors for lake development, the complexity of community trends even in relatively simple systems (invertebrates are the top predators in the lake) and the challenges of deriving palaeoclimate inferences from sediment records in low arctic freshwater lakes