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Sökning: WFRF:(Knutson T) > (2020-2023)

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  • Garmestani, A., et al. (författare)
  • Panarchy : opportunities and challenges for ecosystem management
  • 2020
  • Ingår i: Frontiers in Ecology and the Environment. - : Wiley. - 1540-9295 .- 1540-9309. ; 18:10, s. 576-583
  • Tidskriftsartikel (refereegranskat)abstract
    • Addressing unexpected events and uncertainty represents one of the grand challenges of the Anthropocene, yet ecosystem management is constrained by existing policy and laws that were not formulated to deal with today's accelerating rates of environmental change. In many cases, managing for simple regulatory standards has resulted in adverse outcomes, necessitating innovative approaches for dealing with complex social–ecological problems. We highlight a project in the US Great Plains where panarchy – a conceptual framework that emerged from resilience – was implemented at project onset to address the continued inability to halt large‐scale transition from grass‐to‐tree dominance in central North America. We review how panarchy was applied, the initial outcomes and evidence for policy reform, and the opportunities and challenges for which it could serve as a useful model to contrast with traditional ecosystem management approaches.
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3.
  • Zivanovic, Andrej, et al. (författare)
  • Co-evolution of AR gene copy number and structural complexity in endocrine therapy resistant prostate cancer
  • 2023
  • Ingår i: NAR Cancer. - : Oxford University Press. - 2632-8674. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Androgen receptor (AR) inhibition is standard of care for advanced prostate cancer (PC). However, efficacy is limited by progression to castration-resistant PC (CRPC), usually due to AR re-activation via mechanisms that include AR amplification and structural rearrangement. These two classes of AR alterations often co-occur in CRPC tumors, but it is unclear whether this reflects intercellular or intracellular heterogeneity of AR. Resolving this is important for developing new therapies and predictive biomarkers. Here, we analyzed 41 CRPC tumors and 6 patient-derived xenografts (PDXs) using linked-read DNA-sequencing, and identified 7 tumors that developed complex, multiply-rearranged AR gene structures in conjunction with very high AR copy number. Analysis of PDX models by optical genome mapping and fluorescence in situ hybridization showed that AR residing on extrachromosomal DNA (ecDNA) was an underlying mechanism, and was associated with elevated levels and diversity of AR expression. This study identifies co-evolution of AR gene copy number and structural complexity via ecDNA as a mechanism associated with endocrine therapy resistance.
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