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Sökning: WFRF:(Brewer Carole) > Naturvetenskap

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1.
  • Maxwell, Christopher A., et al. (författare)
  • Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
  • 2011
  • Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
  • 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.
  • Costanza, Robert, et al. (författare)
  • Developing an Integrated History and future of People on Earth (IHOPE)
  • 2012
  • Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 4:1, s. 106-114
  • Tidskriftsartikel (refereegranskat)abstract
    • The Integrated History and future of People on Earth (IHOPE) initiative is a global network of researchers and research projects with its International Program Office (IPO) now based at the Stockholm Resilience Center (SRC), Uppsala University, Arizona State University, Portland State University, and the Australian National University. Research linked to IHOPE demonstrates that Earth system changes in the past have been strongly associated with changes in the coupled human-environment system. IHOPE supports integrating knowledge and resources from the biophysical and the social sciences and the humanities to address analytical and interpretive issues associated with coupled human-earth system dynamics. This integration of human history and Earth system history is a timely and important task. Until recently, however, there have been few attempts at such integration. IHOPE will create frameworks that can be used to help achieve this integration. The overarching goal is to produce a rich understanding of the relationships between environmental and human processes over the past millennia. HOPE recognizes that one major challenge for reaching this goal is developing 'workable' terminology that can be accepted by scholars of all disciplines. The specific objectives for IHOPE are to identify slow and rapidly moving features of complex social-ecological systems, on local to continental spatial scales, which induce resilience, stress, or collapse in linked systems of humans in nature. These objectives will be reached by exploring innovative ways of conducting interdisciplinary and transdisciplinary science, including theory, case studies, and integrated modeling. Examples of projects underway to implement this initiative are briefly discussed.
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3.
  • Sörlin, Sverker, et al. (författare)
  • Toward an Integrated History to Guide the Future
  • 2011
  • Ingår i: Ecology & Society. - 1708-3087. ; 16:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Many contemporary societal challenges manifest themselves in the domain of human–environment interactions.There is a growing recognition that responses to these challenges formulated within current disciplinary boundaries, in isolationfrom their wider contexts, cannot adequately address them. Here, we outline the need for an integrated, transdisciplinary synthesisthat allows for a holistic approach, and, above all, a much longer time perspective. We outline both the need for and thefundamental characteristics of what we call “integrated history.” This approach promises to yield new understandings of therelationship between the past, present, and possible futures of our integrated human–environment system. We recommend aunique new focus of our historical efforts on the future, rather than the past, concentrated on learning about future possibilitiesfrom history. A growing worldwide community of transdisciplinary scholars is forming around building this Integrated Historyand future of People on Earth (IHOPE). Building integrated models of past human societies and their interactions with theirenvironments yields new insights into those interactions and can help to create a more sustainable and desirable future. Theactivity has become a major focus within the global change community.
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