| 1. |
- Bini, Monica, et al.
(författare)
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The 4.2 ka BP Event in the Mediterranean region : An overview
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:2, s. 555-577
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Tidskriftsartikel (refereegranskat)abstract
- The Mediterranean region and the Levant have returned some of the clearest evidence of a climatically dry period occurring around 4200 years ago. However, some regional evidence is controversial and contradictory, and issues remain regarding timing, progression, and regional articulation of this event. In this paper, we review the evidence from selected proxies (sea-surface temperature, precipitation, and temperature reconstructed from pollen, δ 18 O on speleothems, and δ 18 O on lacustrine carbonate) over the Mediterranean Basin to infer possible regional climate patterns during the interval between 4.3 and 3.8 ka. The values and limitations of these proxies are discussed, and their potential for furnishing information on seasonality is also explored. Despite the chronological uncertainties, which are the main limitations for disentangling details of the climatic conditions, the data suggest that winter over the Mediterranean involved drier conditions, in addition to already dry summers. However, some exceptions to this prevail - where wetter conditions seem to have persisted - suggesting regional heterogeneity in climate patterns. Temperature data, even if sparse, also suggest a cooling anomaly, even if this is not uniform. The most common paradigm to interpret the precipitation regime in the Mediterranean - a North Atlantic Oscillation-like pattern - is not completely satisfactory to interpret the selected data.
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| 2. |
- 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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