| 1. |
- Wikström, Frida Hasslung, et al.
(author)
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Structure-dependent modulation of alpha interferon production by porcine circovirus 2 oligodeoxyribonucleotide and CpG DNAs in porcine peripheral blood mononuclear cells.
- 2007
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In: Journal of virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 81:10, s. 4919-27
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Journal article (peer-reviewed)abstract
- DNA sequences containing CpG motifs are recognized as immunomodulators in several species. Phosphodiester oligodeoxyribonucleotides (ODNs) representing sequences from the genome of porcine circovirus type 2 (PCV2) have been identified as potent inducers (ODN PCV2/5) or inhibitors (ODN PCV2/1) of alpha interferon (IFN-alpha) production by porcine peripheral blood mononuclear cells (poPBMCs) in vitro. In this study, the IFN-alpha-inducing or -inhibitory activities of specific phosphodiester ODNs were demonstrated to be dependent on their ability to form secondary structures. When a poly(G) sequence was added to a stimulatory self-complementary ODN, high levels of IFN-alpha were elicited, and the induction was not dependent on pretreatment with the transfecting agent Lipofectin. In addition, the IFN-alpha-inducing ODN required the presence of an intact CpG dinucleotide, whereas the inhibitory activity of ODN PCV2/1 was not affected by methylation or removal of the central CpG dinucleotide. Of particular significance, the IFN-alpha inhibition elicited by ODN PCV2/1 was only effective against induction stimulated by DNA control inducers and not RNA control inducers, indicating activity directed to TLR9 signaling. The PCV2 genome as a whole was demonstrated to induce IFN-alpha in cultures of poPBMCs, and the presence of immune modulatory sequences within the genome of PCV2 may, therefore, have implications with regard to the immune evasion mechanisms utilized by PCV2.
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| 2. |
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| 3. |
- Gawel, Danuta, et al.
(author)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Journal article (peer-reviewed)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 4. |
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| 5. |
- Magnusson, Mattias, et al.
(author)
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Importance of CpG dinucleotides in activation of natural IFN-alpha-producing cells by a lupus-related oligodeoxynucleotide
- 2001
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In: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 54:6, s. 543-550
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Journal article (peer-reviewed)abstract
- The oligodeoxyribonucleotide (ODN) 5-TTTTCAATTCGAAGATGAAT-3 (ODN H), identified in systemic lupus erythematosus (SLE) serum, induced the production of interferon (IFN)-alpha in human peripheral blood mononuclear cells (PBMC) when combined with lipofectin. Flow cytometric analysis with staining for surface antigens and intracellular IFN-alpha, showed that the IFN-alpha -producing cells (IPC) were the natural IPC, also termed type 2 dendritic cell precursors (pDC2) or plasmacytoid monocytes. The importance of unmethylated CpG dinucleotides for the interferogenic activity of ODN was studied. Methylation of CpG impaired the activity of single-stranded (ss) ODN H, but increased that of the complementary ssODN I. Furthermore, CpG-methylated double-stranded (ds) ODN H-met-I-met lost, but hemimethylated dsODN H-I-met retained interferogenic activity. Inversion of the CpG to GpC had no effect on the interferogenic activity of ssODN H, increased that of ssODN I, however abolished the activity of dsODN H-I. Alteration of the CpG in ODN H to ApG and in the ODN I to CpT destroyed their activity. The induction of IFN-alpha is therefore sequence-specific, but unmethylated CpGs are not always required, especially not in ssODNs. Interferogenic DNA sequences could therefore be more frequent in eukaryotic genomes than previously thought and their capacity to activate natural IPC may have implications for immune responses to microbial antigens and nuclear autoantigens.
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| 6. |
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| 7. |
- Adolfsson, Daniel, 1992-, et al.
(author)
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TBV Radar SLAM - Trust but Verify Loop Candidates
- 2023
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In: IEEE Robotics and Automation Letters. - : IEEE. - 2377-3766. ; 8:6, s. 3613-3620
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Journal article (peer-reviewed)abstract
- Robust SLAM in large-scale environments requires fault resilience and awareness at multiple stages, from sensing and odometry estimation to loop closure. In this work, we present TBV (Trust But Verify) Radar SLAM, a method for radar SLAM that introspectively verifies loop closure candidates. TBV Radar SLAM achieves a high correct-loop-retrieval rate by combining multiple place-recognition techniques: tightly coupled place similarity and odometry uncertainty search, creating loop descriptors from origin-shifted scans, and delaying loop selection until after verification. Robustness to false constraints is achieved by carefully verifying and selecting the most likely ones from multiple loop constraints. Importantly, the verification and selection are carried out after registration when additional sources of loop evidence can easily be computed. We integrate our loop retrieval and verification method with a robust odometry pipeline within a pose graph framework. By evaluation on public benchmarks we found that TBV Radar SLAM achieves 65% lower error than the previous state of the art. We also show that it generalizes across environments without needing to change any parameters. We provide the open-source implementation at https://github.com/dan11003/tbv_slam_public
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| 8. |
- Akesson, Alfred, et al.
(author)
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ComPOS : Composing Oblivious Services
- 2019
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In: 2019 IEEE International Conference on Pervasive Computing and Communications Workshops, PerCom Workshops 2019. - 9781538691519 ; , s. 132-138
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Conference paper (peer-reviewed)abstract
- Future internet-of-things systems need to be able to combine heterogeneous services and support weak connectivity. In this paper, we introduce ComPOS, a new domain-specific language for composing services in IoT systems. We show how Maria, a bird watcher, can use ComPOS to build a system that allows her to spy on birds in the garden while she is not at home. We demonstrate how ComPOS handles the unpredictable nature of IoT system by analysing in what cases Maria's system is still useful when some devices are unavailable.
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| 9. |
- Ali, Abukar, 1988, et al.
(author)
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CTLA4-Ig but not anti-TNF therapy promotes staphylococcal septic arthritis in mice.
- 2015
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In: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:8, s. 1308-1316
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Journal article (peer-reviewed)abstract
- The development of biologics has greatly increased the quality of life as well as the life expectancy of many RA patients. However, a large number of these patients are at an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-TNF versus CTLA4-Ig treatment on both immunological response and host defense in a murine model of septic arthritis.
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| 10. |
- Ali, Abukar, 1988, et al.
(author)
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IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.
- 2015
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Journal article (peer-reviewed)abstract
- Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.
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