| 1. |
- Alves, A. C., et al.
(author)
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Dysregulation of Complement System and CD4+T Cell Activation Pathways Implicated in Allergic Response
- 2013
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Journal article (peer-reviewed)abstract
- Allergy is a complex disease that is likely to involve dysregulated CD4+ T cell activation. Here we propose a novel methodology to gain insight into how coordinated behaviour emerges between disease-dysregulated pathways in response to pathophysiological stimuli. Using peripheral blood mononuclear cells of allergic rhinitis patients and controls cultured with and without pollen allergens, we integrate CD4+ T cell gene expression from microarray data and genetic markers of allergic sensitisation from GWAS data at the pathway level using enrichment analysis; implicating the complement system in both cellular and systemic response to pollen allergens. We delineate a novel disease network linking T cell activation to the complement system that is significantly enriched for genes exhibiting correlated gene expression and protein-protein interactions, suggesting a tight biological coordination that is dysregulated in the disease state in response to pollen allergen but not to diluent. This novel disease network has high predictive power for the gene and protein expression of the Th2 cytokine profile (IL-4, IL-5, IL-10, IL-13) and of the Th2 master regulator (GATA3), suggesting its involvement in the early stages of CD4+ T cell differentiation. Dissection of the complement system gene expression identifies 7 genes specifically associated with atopic response to pollen, including C1QR1, CFD, CFP, ITGB2, ITGAX and confirms the role of C3AR1 and C5AR1. Two of these genes (ITGB2 and C3AR1) are also implicated in the network linking complement system to T cell activation, which comprises 6 differentially expressed genes. C3AR1 is also significantly associated with allergic sensitisation in GWAS data.
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| 2. |
- Barrenäs, Fredrik, et al.
(author)
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Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
- 2012
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In: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X .- 1465-6914. ; 13:6, s. R46-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases.RESULTS: We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined small interfering RNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases.CONCLUSIONS: Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.
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| 3. |
- Ramasamy, Madhumidha, et al.
(author)
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Influence of Microstructure and Surface Activation of Dual-Phase Membrane Ce0.8Gd0.2O2−δ–FeCo2O4 on Oxygen Permeation
- 2016
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In: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 99:1, s. 349-355
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Journal article (peer-reviewed)abstract
- Dual-phase oxygen transport membranes are fast-growing research interest for application in oxyfuel combustion process. One such potential candidate is CGO-FCO (60 wt% Ce0.8Gd0.2O2−δ–40 wt% FeCo2O4) identified to provide good oxygen permeation flux with substantial stability in harsh atmosphere. Dense CGO-FCO membranes of 1 mm thickness were fabricated by sintering dry pellets pressed from powders synthesized by one-pot method (modified Pechini process) at 1200°C for 10 h. Microstructure analysis indicates presence of a third orthorhombic perovskite phase in the sintered composite. It was also identified that the spinel phase tends to form an oxygen deficient phase at the grain boundary of spinel and CGO phases. Surface exchange limitation of the membranes was overcome by La0.6Sr0.4Co0.2Fe0.8O3−δ (LSCF) porous layer coating over the composite. The oxygen permeation flux of the CGO-FCO screen printed with a porous layer of 10 μm thick LSCF is 0.11 mL/cm2 per minute at 850°C with argon as sweep and air as feed gas at the rates of 50 and 250 mL/min.
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