| 1. |
- Bagdonaite, Ieva, et al.
(författare)
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Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Viral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered keratinocyte library delineating human glycosylation pathways to uncover roles of specific glycans at different stages of herpes simplex virus type 1 (HSV-1) infectious cycle. We show the importance of cellular glycosaminoglycans and glycosphingolipids for HSV-1 attachment, N-glycans for entry and spread, and O-glycans for propagation. While altered virion surface structures have minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affects glycoprotein surface expression and function. In conclusion, the data demonstrates the importance of specific glycans in a clinically relevant human model of HSV-1 infection and highlights the utility of genetic engineering to elucidate the roles of specific viral and cellular carbohydrate structures.
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| 2. |
- Rudjord-Levann, Asha M., et al.
(författare)
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Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1
- 2023
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Ingår i: iScience. - 2589-0042. ; 26:7
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we analyzed the expression of galectin-1 and found upregulation of galectin-1 in the extracellular matrix across multiple tumors. Performing an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galectin-1, we show that galectin-1 induces a tumor-associated macrophage phenotype with increased expression of key immune checkpoint protein programmed cell death 1 ligand 1 (PD-L1/CD274) and immunomodulator indoleamine 2,3-dioxygenase-1 (IDO1). Galectin-1 induced IDO1 and its active metabolite kynurenine in a dose-dependent manner through JAK/STAT signaling. In a 3D organotypic tissue model system equipped with genetically engineered tumorigenic epithelial cells, we analyzed the cellular source of galectin-1 in the extracellular matrix and found that galectin-1 is derived from epithelial and stromal cells. Our results highlight the potential of targeting galectin-1 in immunotherapeutic treatment of human cancers.
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| 3. |
- Wandall, Rasmus H., et al.
(författare)
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Hiring and learning strategies in prosecution services
- 2021
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Ingår i: The Oxford Handbook of Prosecutors and Prosecution. - : Oxford University Press. - 9780190905422 ; , s. 207-226
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Bokkapitel (refereegranskat)abstract
- The chapter provides a comparative overview of current hiring and learning strategies in prosecution services. It draws on empirical examples from all parts of the world. Specifically, the chapter compares the hiring of chief prosecutors and frontline prosecutors, it compares how learning is organized and carried out, and it describes and discusses the most significant individual methods of learning currently applied by prosecution services. The comparison shows some level of convergence of techniques and strategies. However, prosecution services continue to vary significantly in how they organize and carry out hiring and in how prosecutors learn. To some degree these variations reflect different levels of professionalization and legal accountability, but they also reflect the markedly different ideals, roles, and functions that drive prosecution services in different societies and legal cultures. These differences make for very different conditions under which new and better ways of hiring and learning can be implemented with a view to ensure qualified and legitimate prosecution services.
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