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- Hildebrandt, Franziska, et al.
(författare)
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Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Upon infecting its vertebrate host, the malaria parasite initially invades the liver where it undergoes massive replication, whilst remaining clinically silent. The coordination of host responses across the complex liver tissue during malaria infection remains unexplored. Here, we perform spatial transcriptomics in combination with single-nuclei RNA sequencing over multiple time points to delineate host-pathogen interactions across Plasmodium berghei-infected liver tissues. Our data reveals significant changes in spatial gene expression in the malaria-infected tissues. These include changes related to lipid metabolism in the proximity to sites of Plasmodium infection, distinct inflammation programs between lobular zones, and regions with enrichment of different inflammatory cells, which we term 'inflammatory hotspots'. We also observe significant upregulation of genes involved in inflammation in the control liver tissues of mice injected with mosquito salivary gland components. However, this response is considerably delayed compared to that observed in P. berghei-infected mice. Our study establishes a benchmark for investigating transcriptome changes during host-parasite interactions in tissues, it provides informative insights regarding in vivo study design linked to infection and offers a useful tool for the discovery and validation of de novo intervention strategies aimed at malaria liver stage infection.
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| 2. |
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| 3. |
- Urrutia Iturritza, Miren, et al.
(författare)
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An automated microfluidic diagnostics pipeline for infectious disease detection in low resource settings
- 2020
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Ingår i: MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. ; , s. 1197-1198
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Konferensbidrag (refereegranskat)abstract
- While diagnostics are critical for accurate and timely diagnosis, gold-standard diagnostic tests are commonly high- performance laboratory-based tests that require multi-step protocols for complex sample processing and highly trained personnel, both scarce in low-resource settings. Here, we address the need for an easy-to-use, rapid and reliable diagnostic testing pipeline by presenting a solution combining open-source modular automation and automation compatible microfluidics, easily adaptable to a pipeline for infectious diseases diagnosis. We demonstrate an automation compatible microfluidics pipeline for Neisseria meningitidis diagnosis by on-chip nucleic acids isolation and isothermal amplification, as well as pathogen detection on a paper-based microarray.
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| 4. |
- Urrutia Iturritza, Miren, et al.
(författare)
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An Automated Versatile Diagnostic Workflow for Infectious Disease Detection in Low-Resource Settings
- 2024
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Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory automation effectively increases the throughput in sample analysis, reduces human errors in sample processing, as well as simplifies and accelerates the overall logistics. Automating diagnostic testing workflows in peripheral laboratories and also in near-patient settings -like hospitals, clinics and epidemic control checkpoints- is advantageous for the simultaneous processing of multiple samples to provide rapid results to patients, minimize the possibility of contamination or error during sample handling or transport, and increase efficiency. However, most automation platforms are expensive and are not easily adaptable to new protocols. Here, we address the need for a versatile, easy-to-use, rapid and reliable diagnostic testing workflow by combining open-source modular automation (Opentrons) and automation-compatible molecular biology protocols, easily adaptable to a workflow for infectious diseases diagnosis by detection on paper-based diagnostics. We demonstrated the feasibility of automation of the method with a low-cost Neisseria meningitidis diagnostic test that utilizes magnetic beads for pathogen DNA isolation, isothermal amplification, and detection on a paper-based microarray. In summary, we integrated open-source modular automation with adaptable molecular biology protocols, which was also faster and cheaper to perform in an automated than in a manual way. This enables a versatile diagnostic workflow for infectious diseases and we demonstrated this through a low-cost N. meningitidis test on paper-based microarrays.
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