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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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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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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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Sylwan, Lina, et al.
(författare)
Identification of bases required for P2 Integrase core-binding and recombination
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
Temperate coliphage P2 integrates its genome into the host chromosome upon lysogenization via a site-specific recombination event mediated by an integrase belonging to the complex family of tyrosine recombinases. The host integration site attB (BOB´) is localized in the end of the cyaR gene and share 27 nucleotides with the core of attP (COC´). In the present study we determine the minimal attB site using an in vivo recombination assay and 10 nt on the left side (B) are found to be nonessential for recombination. We show that the integrase has higher affinity for the right side (B´) compared to B and that artificial B´OB´ and an attP site with a matching core (C´OC´) are efficient substrates for recombination in vitro. We have analyzed single nucleotides in attB and find that sequence homology within a non-centrally located quadruplet in the hypotetical overlap region is essential for efficient recombination in vivo.
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Amer, Ayad, 1980-, et al.
(författare)
Functional consequences of site-directed mutagenesis in the C-terminus of YopN, a Yersinia pseudotuberculosis regulator of Yop secretion
Annan publikation (övrigt vetenskapligt/konstnärligt) abstract
Pathogenic Yersinia spp. utilizes the Ysc-Yop type III secretion system to targetYop effector proteins into the cytosol of host immune cells. Internalizedeffectors alter specific signaling pathways to neutralize immune cell-dependentphagocytosis, killing and pro-inflammatory responsiveness. This enablesextracellular bacterial multiplication and survival in immune tissue. Central tothe temporal control of Yop type III secretion is the regulator YopN. Incomplex with TyeA, YopN acts to plug the inner face of the type III secretionchannel, denying entry to other Yop substrates until after YopN has beensecreted. A +1 frameshift event in the 3-prime end of yopN results in thesynthesis of a singular secreted YopN-TyeA polypeptide chimera that retainssome regulatory function. As the C-terminal coding sequence of YopN in thishybrid product differs greatly from native sequence, we used site-directedmutagenesis to determine the functional significance of this segment. YopNtruncated at residue 287 or containing a shuffled sequence covering 288 to 293retains full function both in vitro and in vivo. Thus, the extreme C-terminus isapparently superfluous to YopN function. In contrast, a YopN varianttruncated after residue 278 was completely unstable, and these bacteria hadlost all control of T3S activity, and failed to defend against immune cell killing.Interestingly, inclusion of a shuffled sequence from residues 279 to 287recovered some T3S control over function. Hence, the YopN segmentencompassing 279 to 287 is essential for full function, although the exact aminoacid sequence is less important.
