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- Mezger, A, et al.
(författare)
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High-throughput chromatin accessibility profiling at single-cell resolution
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3647-
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Tidskriftsartikel (refereegranskat)abstract
- Here we develop a high-throughput single-cell ATAC-seq (assay for transposition of accessible chromatin) method to measure physical access to DNA in whole cells. Our approach integrates fluorescence imaging and addressable reagent deposition across a massively parallel (5184) nano-well array, yielding a nearly 20-fold improvement in throughput (up to ~1800 cells/chip, 4–5 h on-chip processing time) and library preparation cost (~81¢ per cell) compared to prior microfluidic implementations. We apply this method to measure regulatory variation in peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of single cells by hematopoietic cell type.
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- Wohlrab, S., et al.
(författare)
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Ocean acidification increases domoic acid contents during a spring to summer succession of coastal phytoplankton
- 2020
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Ingår i: Harmful Algae. - : Elsevier BV. - 1568-9883. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Enrichment of the oceans with CO2 may be beneficial for some marine phytoplankton, including harmful algae. Numerous laboratory experiments provided valuable insights into the effects of elevated pCO(2) on the growth and physiology of harmful algal species, including the production of phycotoxins. Experiments close to natural conditions are the next step to improve predictions, as they consider the complex interplay between biotic and abiotic factors that can confound the direct effects of ocean acidification. We therefore investigated the effect of ocean acidification on the occurrence and abundance of phycotoxins in bulk plankton samples during a long-term mesocosm experiment in the Gullmar Fjord, Sweden, an area frequently experiencing harmful algal blooms. During the experimental period, a total of seven phycotoxin-producing harmful algal genera were identified in the fjord, and in accordance, six toxin classes were detected. However, within the mesocosms, only domoic acid and the corresponding producer Pseudo-nitzschia spp. was observed. Despite high variation within treatments, significantly higher particulate domoic acid contents were measured in the mesocosms with elevated pCO(2). Higher particulate domoic acid contents were additionally associated with macronutrient limitation. The risks associated with potentially higher phycotoxin levels in the future ocean warrants attention and should be considered in prospective monitoring strategies for coastal marine waters.
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- Bekkhus, T., et al.
(författare)
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Automated detection of vascular remodeling in tumor-draining lymph nodes by the deep-learning tool HEV-finder
- 2022
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 258:1, s. 4-11
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Tidskriftsartikel (refereegranskat)abstract
- Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. (c) 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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- Connell, H., et al.
(författare)
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Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract
- 1996
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 93:18, s. 9827-9832
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 fimbriae are adhesion organelles expressed by many Gram-negative bacteria. They facilitate adherence to mucosal surfaces and inflammatory cells in vitro, but their contribution to virulence has not been defined. This study presents evidence that type 1 fimbriae increase the virulence of Escherichia coli for the urinary tract by promoting bacterial persistence and enhancing the inflammatory response to infection. In a clinical study, we observed that disease severity was greater in children infected with E. coli O1:K1:H7 isolates expressing type 1 fimbriae than in those infected with type 1 negative isolates of the same serotype. The E. coli O1:K1:H7 isolates had the same electrophoretic type, were hemolysin-negative, expressed P fimbriae, and carried the fim DNA sequences. When tested in a mouse urinary tract infection model, the type 1-positive E. coli O1:K1:H7 isolates survived in higher numbers, and induced a greater neutrophil influx into the urine, than O1:K1:H7 type 1-negative isolates. To confirm a role of type 1 fimbriae, a fimH null mutant (CNI016) was constructed from an O1:K1:H7 type 1-positive parent. E. coli CNI016 had reduced survival and inflammatogenicity in the mouse urinary tract infection model. E. coli CNI016 reconstituted with type 1 fimbriae (E. coli CN1018) had restored virulence similar to that of the wild- type parent strain. These results show that type 1 fimbriae in the genetic background of a uropathogenic strain contribute to the pathogenesis of E. coli in the urinary tract.
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