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- Hannan, T. J., et al.
(författare)
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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
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- Antonelli, Alexandre, 1978, et al.
(författare)
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Geological and climatic influences on mountain biodiversity
- 2018
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Mountains are key features of the Earth's surface and host a substantial proportion of the world's species. However, the links between the evolution and distribution of biodiversity and the formation of mountains remain poorly understood. Here, we integrate multiple datasets to assess the relationships between species richness in mountains, geology and climate at global and regional scales. Specifically, we analyse how erosion, relief, soil and climate relate to the geographical distribution of terrestrial tetrapods, which include amphibians, birds and mammals. We find that centres of species richness correlate with areas of high temperatures, annual rainfall and topographic relief, supporting previous studies. We unveil additional links between mountain-building processes and biodiversity: species richness correlates with erosion rates and heterogeneity of soil types, with a varying response across continents. These additional links are prominent but under-explored, and probably relate to the interplay between surface uplift, climate change and atmospheric circulation through time. They are also influenced by the location and orientation of mountain ranges in relation to air circulation patterns, and how species diversification, dispersal and refugia respond to climate change. A better understanding of biosphere-lithosphere interactions is needed to understand the patterns and evolution of mountain biodiversity across space and time.
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- Riehl, Jennifer F. L., et al.
(författare)
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Genomic and transcriptomic analyses reveal polygenic architecture for ecologically important traits in aspen (Populus tremuloides Michx.)
- 2023
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Intraspecific genetic variation in foundation species such as aspen (Populus tremuloides Michx.) shapes their impact on forest structure and function. Identifying genes underlying ecologically important traits is key to understanding that impact. Previous studies, using single-locus genome-wide association (GWA) analyses to identify candidate genes, have identified fewer genes than anticipated for highly heritable quantitative traits. Mounting evidence suggests that polygenic control of quantitative traits is largely responsible for this “missing heritability” phenomenon. Our research characterized the genetic architecture of 30 ecologically important traits using a common garden of aspen through genomic and transcriptomic analyses. A multilocus association model revealed that most traits displayed a highly polygenic architecture, with most variation explained by loci with small effects (likely below the detection levels of single-locus GWA methods). Consistent with a polygenic architecture, our single-locus GWA analyses found only 38 significant SNPs in 22 genes across 15 traits. Next, we used differential expression analysis on a subset of aspen genets with divergent concentrations of salicinoid phenolic glycosides (key defense traits). This complementary method to traditional GWA discovered 1243 differentially expressed genes for a polygenic trait. Soft clustering analysis revealed three gene clusters (241 candidate genes) involved in secondary metabolite biosynthesis and regulation. Our work reveals that ecologically important traits governing higher-order community- and ecosystem-level attributes of a foundation forest tree species have complex underlying genetic structures and will require methods beyond traditional GWA analyses to unravel.
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