Cross-species high-resolution transcriptome profiling suggests biomarkers and therapeutic targets for ulcerative colitis

Background: Ulcerative colitis (UC) is a disorder with unknown etiology, and animal models play an essential role in studying its molecular pathophysiology. Here, we aim to identify common conserved pathological UC-related gene expression signatures between humans and mice that can be used as treatment targets and/or biomarker candidates.Methods: To identify differentially regulated protein-coding genes and non-coding RNAs, we sequenced total RNA from the colon and blood of the most widely used dextran sodium sulfate Ulcerative colitis mouse. By combining this with public human Ulcerative colitis data, we investigated conserved gene expression signatures and pathways/biological processes through which these genes may contribute to disease development/progression.Results: Cross-species integration of human and mouse Ulcerative colitis data resulted in the identification of 1442 genes that were significantly differentially regulated in the same direction in the colon and 157 in blood. Of these, 51 genes showed consistent differential regulation in the colon and blood. Less known genes with importance in disease pathogenesis, including SPI1, FPR2, TYROBP, CKAP4, MCEMP1, ADGRG3, SLC11A1, and SELPLG, were identified through network centrality ranking and validated in independent human and mouse cohorts.Conclusion: The identified Ulcerative colitis conserved transcriptional signatures aid in the disease phenotyping and future treatment decisions, drug discovery, and clinical trial design

The economic impact of decreased mortality and increased growth associated with preventing, replacing or improving current methods for delousing farmed Atlantic salmon in Norway

Impacts of salmon lice is a major concern for a sustainable production of farmed Atlantic salmon in Norway. Most treatment methods for removal of salmon lice have associated increased mortality and decreased growth in a period after delousing, which affects the profitability of the farmer, and causes poor welfare and sustainability. In addition, the variance in mortality and growth, especially after non-medicinal treatment methods, is high, which makes it hard for a farmer to decide which control measure to apply to keep lice levels below the legal limit. In this study, we have applied a stochastic partial budget approach to assess the economic impact of reducing mortality and increasing growth of farmed Atlantic salmon by preventing, replacing and improving current delousing methods in Norway. We have simulated a production cycle of two different smolt-groups to find the outcome (harvested biomass, average end weight of the salmon, number of dead fish and feed consumption) of production cycles without or with two, three or four delousing treatments in the on-growing phase at sea. The results suggest that accounting for the biological losses associated with lice treatments is important when making choices of delousing strategies. The biological costs of increased mortality and decreased growth associated with especially non-medicinal treatments are expected to be high, but varies substantially. Therefore, the economic benefit of preventing or improving can also be high. The calculations imply that salmon producers could invest a considerable amount in measures for prevention or improvement of thermal treatments before break-even. For example could a farmer use on average 535,313 €/cage/ 1-yearling production in measure to prevent four thermal treatments before it is no longer economical beneficial. Depending on the performance of the four thermal treatments a farmer could use from 319,196–737,934 €/cage/ 1-yearling production on measures of improvement. Replacing one thermal treatment with another immediate treatment method has a minor economic benefit. The results further shows that sales value and feed consumption constitutes the largest share of the change in profit between different treatment regimes. The results from this study also show that not taking into account the risk of mortality and reduced growth associated with the different treatment methods of delousing, could lead to underestimating the benefit of improving, preventing and replacing treatments.publishedVersio

Cross-species high-resolution transcriptome profiling suggests biomarkers and therapeutic targets for ulcerative colitis

Background: Ulcerative colitis (UC) is a disorder with unknown etiology, and animal models play an essential role in studying its molecular pathophysiology. Here, we aim to identify common conserved pathological UC-related gene expression signatures between humans and mice that can be used as treatment targets and/or biomarker candidates. Methods: To identify differentially regulated protein-coding genes and non-coding RNAs, we sequenced total RNA from the colon and blood of the most widely used dextran sodium sulfate Ulcerative colitis mouse. By combining this with public human Ulcerative colitis data, we investigated conserved gene expression signatures and pathways/biological processes through which these genes may contribute to disease development/progression. Results: Cross-species integration of human and mouse Ulcerative colitis data resulted in the identification of 1442 genes that were significantly differentially regulated in the same direction in the colon and 157 in blood. Of these, 51 genes showed consistent differential regulation in the colon and blood. Less known genes with importance in disease pathogenesis, including SPI1, FPR2, TYROBP, CKAP4, MCEMP1, ADGRG3, SLC11A1, and SELPLG, were identified through network centrality ranking and validated in independent human and mouse cohorts. Conclusion: The identified Ulcerative colitis conserved transcriptional signatures aid in the disease phenotyping and future treatment decisions, drug discovery, and clinical trial design