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Karén, Jakob, 1973-, et al.
(författare)
Defining the pericyte to fibroblast lineage
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
In the present study placental tissues were characterized in vivo with regards to markers expressed on pericytes, fibroblasts and collagen type I synthesis. Microvascular fragments (MVFs) isolated from human placentas had a phenotypical marker profile consistent with microvessels in situ. Cells emerging from MVFs from placenta express a marker profile consistent with a pericyte phenotype. Temporal studies identified three optimal time points (T0, T1 and T2) subsequent to the onset of cells emerging from MVFs for further analysis with regards to divergence in marker expression profiles. T0, T1 and T2 time points contained a population of cells with a cellular phenotype consistent with mesenchymal stem/progenitor cells, activated microvascular pericytes and mature connective tissue cells. Three discernable subpopulations of cells were identified i.e. Stro-1+/CD146+/podoplanin-, Stro-1-/CD146+/podoplanin- and Stro-1-/CD146-/podoplanin+ cells. Flow cytometry analysis allowed for the Stro-1-/CD146+/podoplanin- and Stro-1-/CD146-/podplanin+ cell populations to be further divided into 2 subgroups based on the expression of desmin, αSMA and TE-7. Five steps in the differentiation process from mesenchymal stem/progenitor cell to collagen type I producing fibroblast and the order by which they progressed could be defined by re-diversification studies i.e. ability of one population of cells to give rise to the other population of cells. Two in vivo experimental systems, TPA induced inflammation and excisional cutaneous wound healing were analyzed for the existence of slow cycling cells. The in vivo evidence shows that microvascular pericytes constitute a reservoir of stem/progenitor cells for pro-fibrotic connective tissue cells. This study presents novel evidence for a connective tissue cell lineage originating from a undifferentiated mesenchymal vessel associated cell population that via pericytes differentiate into pro-fibrotic fibroblasts.
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Baudin, Maria, 1982-, et al.
(författare)
Importance of charge interactions in Rift Valley fever virus attachment to host cells
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
The mosquito-borne Rift Valley fever virus (RVFV) cause disease in both humans and animals and can infect a large range of animals as well as humans. Many different cell types are infected both in vivo and in vitro. To enter a cell the virus needs to attach and enter, and this initial binding to the host cell surface could depend on both general mechanisms, and different specific receptors. Our aim was to characterize determinants for RVFV entry into its host cells.To examine RVFV attachment to host cells we based our experimental assay on RVF virus-like particles containing a reporter gene. The enveloped RVFV uses protruding glycoproteins (Gn and Gc) for attachment and entry and to investigate potential virus-cell surface interactions, the net surface charge of the glycoproteins was first calculated. The RVFV glycoprotein Gn had a predicted isoelectric point (pI) of 7.6 and a net positive charge of +6.9 at pH 7.0, suggesting a charge interaction between the Gn ectodomain and the negatively charged cell surface. RVFV Gc on the other hand, was highly negatively charged, -12.8 at neutral pH, most probably reflecting that Gc is not exposed until after receptor binding. To characterize the general conditions needed for RVFV attachment, cells or virus were treated with various compounds. Both sodium chloride and the negatively charged heparin inhibited RVF virus-like particle infection, strongly indicating that viral binding was charge-dependent. Treatment with sodium periodate pointed to a carbohydrate structure as a cellular interaction partner. Removal of sialic acid or heparan sulfate receptors on the cell surface by enzymatic treatment and blocking of the heparan sulfate receptor did not inhibit virus attachment.In conclusion, RVFV binding to host cells was charge dependent and the results point to a carbohydrate structure with negative charge as a potential attachment factor.
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Kazemi Rashed, Salma, et al.
(författare)
English dictionaries, gold and silver standard corpora for biomedical natural language processing related to SARS-CoV-2 and COVID-19
2020
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
Here we present a toolbox for natural language processing tasks related to SARS-CoV-2. It comprises English dictionaries of synonyms for SARS-CoV-2 and COVID-19, a silver standard corpus generated with the dictionaries and a gold standard corpus of 10 Pubmed abstracts manually annotated for disease, virus, symptom and protein/gene terms. This toolbox is freely available on github and can be used for text analytics in a variety of settings related to the COVID-19 crisis. It will be expanded and applied in NLP tasks over the next weeks and the community is invited to contribute.
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Malmberg, Christer, et al.
(författare)
Faster results, higher precision: Evaluating the QuickMIC rapid AST assay in a clinical setting
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
The rapidly changing landscape of antimicrobial resistance poses a challenge for empirical therapy and highlights the need for fast antibiotic susceptibility diagnostics to guide treatment. Traditional methods for antibiotic susceptibility testing (AST) of bacteria such as broth microdilution (BMD) or the disc diffusion method (DDM) are comparatively slow and with high variability. Rapid AST methods under development often trade speed for resolution, sometimes only measuring responses at a single antibiotic concentration. QuickMIC is a recently developed lab-on-a-chip system for rapid AST. Here we evaluate the performance of the QuickMIC method with regard to speed, precision and accuracy in comparison to traditional diagnostic methods. 151 blood cultures of clinical Gram-negative isolates with a high frequency of resistant bacteria were tested with the QuickMIC system and compared with BMD for 12 antibiotics. To investigate sample turnaround time and functionality in a clinical setting, another 41 clinical blood culture samples were acquired from the Uppsala University Hospital and analyzed on site in the clinical laboratory with the QuickMIC system and compared with DDM for 8 antibiotics routinely used in the clinical laboratory. The overall essential agreement between MIC values obtained by QuickMIC and BMD was 83.2%, with times to result of 3 h 2 min (SD: 24.8 min) for the QuickMIC method. For the clinical dataset, the categorical agreement was 94.9%, and the total turnaround time as compared to routine diagnostics reduced by 40% (33 h vs. 55 h). Interexperiment variability was low (average SD: 44.6% from target MIC) compared to the acceptable standard of ±1 log2 unit (-50% to +100% deviation from target MIC) in BMD. We conclude that the QuickMIC method can be used to rapidly guide therapy, and may be especially valuable for antibiotics where wildtype and resistant MIC distributions are close or overlapping or in settings with high background resistance.
