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- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 2. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
- Díaz-Calafat, Joan, et al.
(författare)
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From broadleaves to conifers : The effect of tree composition and density on understory microclimate across latitudes
- 2023
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Ingår i: Agricultural and Forest Meteorology. - 0168-1923 .- 1873-2240. ; 341
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Tidskriftsartikel (refereegranskat)abstract
- Forest canopies buffer the macroclimate and thus play an important role in mitigating climate-warming impacts on forest ecosystems. Despite the importance of the tree layer for understory microclimate buffering, our knowledge about the effects of forest structure, composition and their interactions with macroclimate is limited, especially in mixtures of conifers and broadleaves. Here we studied five mixed forest stands along a 1800 km latitudinal gradient covering a 7°C span in mean annual temperature. In each of these forests we established 40 plots (200 in total), in which air and soil temperatures were measured continuously for at least one year. The plots were located across gradients of forest density and broadleaved proportions (i.e. from open to closed canopies, and from 100% conifer to 100% broadleaved tree dominance). Air minimum, mean and maximum temperature offsets (i.e. difference between macroclimate and microclimate) and soil mean temperature offsets were calculated for the coldest and warmest months. Forest structure, and especially forest density, was the key determinant of understory temperatures. However, the absolute and relative importance of the proportion of broadleaves and forest density differed largely between response variables. Forest density ranged from being independent of, to interacting with, tree species composition. The effect of these two variables was independent of the macroclimate along our latitudinal gradient. Temperature, precipitation, snow depth and wind outside forests affected understory temperature buffering. Finally, we found that the scale at which the overstory affects soil microclimate approximated 6-7 m, whereas for air microclimate this was at least 10 m. These findings have implications for biodiversity conservation and forest management in a changing climate, as they facilitate the projection of understory temperatures in scenarios where both forest structure and macroclimate are dynamic. This is especially relevant given the global importance of ongoing forest conversion from conifers to broadleaves, and vice versa.
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