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- Suzuki, Toshiyasu, et al.
(author)
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b-Catenin Drives Butyrophilin-like Molecule Loss and gd T-cell Exclusion in Colon Cancer
- 2023
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In: CANCER IMMUNOLOGY RESEARCH. - : AMER ASSOC CANCER RESEARCH. - 2326-6066. ; 11:8, s. 1137-1155
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Journal article (peer-reviewed)abstract
- Intraepithelial lymphocytes (IEL) expressing y8 T-cell receptors (y8TCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immu-nosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic y8IELs. In contrast with healthy intestinal or colonic tissue, we found that y8IELs were largely absent from the micro-environment of both mouse and human tumors, and that butyr-ophilin-like (BTNL) molecules, which can critically regulate y8IEL through direct y8TCR interactions, were also downregulated in tumors. We then demonstrated that 13-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased y8IEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of 13-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant 13-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and y8 T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts y8IEL immunosurveillance and furthers cancer progression.
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- Biggs, Reinette, et al.
(author)
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Preparing for the future : teaching scenario planning at the graduate level
- 2010
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In: Frontiers in Ecology and the Environment. - : Wiley. - 1540-9295. ; 8:5, s. 267-273
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Journal article (peer-reviewed)abstract
- Are environmental science students developing the mindsets and obtaining the tools needed to help address the considerable challenges posed by the 21st century? Today's major environmental issues are characterized by high-stakes decisions and high levels of uncertainty. Although traditional scientific approaches are valuable, contemporary environmental issues also require new tools and new ways of thinking. We provide an example of how such new, or “post-normal”, approaches have been taught at the graduate level, through practical application of scenario planning. Surveyed students reported that they found the scenario planning course highly stimulating, thought-provoking, and inspiring. Key learning points included recognizing the need for multiple points of view when considering complex environmental issues, and better appreciating the pervasiveness of uncertainty. Collaborating with non-academic stakeholders was also particularly helpful. Most students left the course feeling more positive about the potential contribution they can make in addressing the environmental challenges that society faces. Read More: http://www.esajournals.org/doi/abs/10.1890/080075
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- Haas, Brian J., et al.
(author)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Journal article (peer-reviewed)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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