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- Chmielowski, Reia, et al.
(författare)
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Duplex structure and Paleocene displacement of the Toyuk thrust zone near the Dalton Highway, north-central Brooks Range
- 2000
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Ingår i: Short Notes on Alaska Geology 1999. - : Alaska Department of Natural Resources. ; , s. 11-32
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Bokkapitel (refereegranskat)abstract
- The Toyuk thrust zone is a regional tectonic boundary in the central Brooks Range of northern Alaska that has been interpreted previously as a single large-displacement fault. Just west of the Dalton Highway, the thrust zone is defined by several north-vergent imbricate thrust faults. These faults have cut detachment folds formed in the competent Kanayut Conglomerate between detachments in the underlying Hunt Fork Shale and overlying Kayak Shale, thereby forming a duplex. The exposed structural geometry suggests two endmember models of duplex geometry. In model one, each linking thrust has roughly the same small displacement and the roof thrust is overlain by a normal stratigraphic succession. In model two, the uppermost and hindmost fault has greater displacement than the other faults and so forms a duplex roof above which the stratigraphic section is duplicated. Discrimination between these models is not possible because the duplex roof has been eroded in the field area.Apatite fission-track analyses of samples collected within the Toyuk thrust zone record two distinct episodes of cooling interpreted to represent unroofing in response to tectonic deformation. The initial episode occurred at ~100 Ma, while the later episode occurred at ~60 Ma. These two cooling/denudation events have been documented previously in the region, but the samples from the thrust zone are the first to document displacement on a specific fault during the ~60 Ma event so far south of the front of the central Brooks Range. The results suggest that at least part of the growth of the Toyuk thrust zone accommodated structural thickening within the orogenic wedge coeval with deformation at the range front.
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| 2. |
- Coyle, Krysta M., et al.
(författare)
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Breast cancer subtype dictates DNA methylation and ALDH1A3-mediated expression of tumor suppressor RARRES1
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:28, s. 44096-44112
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determine patient prognosis and potential options for targeted therapy. Among breast cancer subtypes, tumors of basal-like and claudin-low subtypes are typically associated with worse patient outcomes, are primarily classified as triple-negative breast cancers (TNBC), and cannot be treated with existing hormone-receptor-targeted therapies. Understanding the molecular basis of these subtypes will lead to the development of more effective treatment options for TNBC. In this study, we focus on retinoic acid receptor responder 1 (RARRES1) as a paradigm to determine if breast cancer subtype dictates protein function and gene expression regulation. Patient tumor dataset analysis and gene expression studies of a 26 cell-line panel, representing the five breast cancer subtypes, demonstrate that RARRES1 expression is greatest in basal-like TNBCs. Cell proliferation and tumor growth assays reveal that RARRES1 is a tumor suppressor in TNBC. Furthermore, gene expression studies, Illumina HumanMethylation450 arrays, and chromatin immunoprecipitation demonstrate that expression of RARRES1 is retained in basal-like breast cancers due to hypomethylation of the promoter. Additionally, expression of the cancer stem cell marker, aldehyde dehydrogenase 1A3, which provides the required ligand (retinoic acid) for RARRES1 transcription, is also specific to the basal-like subtype. We functionally demonstrate that the combination of promoter methylation and retinoic acid signaling dictates expression of tumor suppressor RARRES1 in a subtype-specific manner. These findings provide a precedent for a therapeutically-inducible tumor suppressor and suggest novel avenues of therapeutic intervention for patients with basal-like breast cancer.
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