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- Fyhrquist, N, et al.
(författare)
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Microbe-host interplay in atopic dermatitis and psoriasis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4703-
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
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- Tervaniemi, MH, et al.
(författare)
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NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 22745-
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Tidskriftsartikel (refereegranskat)abstract
- Psoriatic skin differs distinctly from normal skin by its thickened epidermis. Most gene expression comparisons utilize full-thickness biopsies, with substantial amount of dermis. We assayed the transcriptomes of normal, lesional and non-lesional psoriatic epidermis, sampled as split-thickness skin grafts, with 5′-end RNA sequencing. We found that psoriatic epidermis contains more mRNA per total RNA than controls and took this into account in the bioinformatic analysis. The approach highlighted innate immunity-related pathways in psoriasis, including NOD-like receptor (NLR) signaling and inflammasome activation. We demonstrated that the NLR signaling genes NOD2, PYCARD, CARD6 and IFI16 are upregulated in psoriatic epidermis and strengthened these findings by protein expression. Interestingly, PYCARD, the key component of the inflammasome, showed an altered expression pattern in the lesional epidermis. The profiling of non-lesional skin highlighted PSORS4 and mitochondrially encoded transcripts, suggesting that their gene expression is altered already before the development of lesions. Our data suggest that all components needed for the active inflammasome are present in the keratinocytes of psoriatic skin. The characterization of inflammasome pathways provides further opportunities for therapy. Complementing previous transcriptome studies, our approach gives deeper insight into the gene regulation in psoriatic epidermis.
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- Bender, Michael A., et al.
(författare)
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The minimum backlog problem
- 2015
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Ingår i: Theoretical Computer Science. - : ELSEVIER SCIENCE BV. - 0304-3975 .- 1879-2294. ; 605, s. 51-61
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Tidskriftsartikel (refereegranskat)abstract
- We study the minimum backlog problem (MBP). This online problem arises, e.g., in the context of sensor networks. We focus on two main variants of MBP. The discrete MBP is a 2-person game played on a graph G = (V, E). The player is initially located at a vertex of the graph. In each time step, the adversary pours a total of one unit of water into cups that are located on the vertices of the graph, arbitrarily distributing the water among the cups. The player then moves from her current vertex to an adjacent vertex and empties the cup at that vertex. The players objective is to minimize the backlog, i.e., the maximum amount of water in any cup at any time. The geometric MBP is a continuous-time version of the MBP: the cups are points in the two-dimensional plane, the adversary pours water continuously at a constant rate, and the player moves in the plane with unit speed. Again, the players objective is to minimize the backlog. We show that the competitive ratio of any algorithm for the MBP has a lower bound of Omega (D), where D is the diameter of the graph (for the discrete MBP) or the diameter of the point set (for the geometric MBP). Therefore we focus on determining a strategy for the player that guarantees a uniform upper bound on the absolute value of the backlog. For the absolute value of the backlog there is a trivial lower bound of Omega (D), and the deamortization analysis of Dietz and Sleator gives an upper bound of O (D log N) for N cups. Our main result is a tight upper bound for the geometric MBP: we show that there is a strategy for the player that guarantees a backlog of O(D), independently of the number of cups. We also study a localized version of the discrete MBP: the adversary has a location within the graph and must act locally (filling cups) with respect to his position, just as the player acts locally (emptying cups) with respect to her position. We prove that deciding the value of this game is PSPACE-hard. (C) 2015 Elsevier B.V. All rights reserved.
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- Efrat, Alon, et al.
(författare)
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Improved Approximation Algorithms for Relay Placement
- 2016
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Ingår i: ACM Transactions on Algorithms. - : ACM Press. - 1549-6325 .- 1549-6333. ; 12:2, s. 20-
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Tidskriftsartikel (refereegranskat)abstract
- In the relay placement problem, the input is a set of sensors and a number r >= 1, the communication range of a relay. In the one-tier version of the problem, the objective is to place a minimum number of relays so that between every pair of sensors there is a path through sensors and/or relays such that the consecutive vertices of the path are within distance r if both vertices are relays and within distance 1 otherwise. The two-tier version adds the restrictions that the path must go through relays, and not through sensors. We present a 3.11-approximation algorithm for the one-tier version and a polynomial-time approximation scheme (PTAS) for the two-tier version. We also show that the one-tier version admits no PTAS, assuming P not equal NP.
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- Kainu, Kati, et al.
(författare)
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Association of psoriasis to PGLYRP and SPRR genes at PSORS4 locus on 1q shows heterogeneity between Finnish, Swedish and Irish families.
- 2009
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Ingår i: Experimental dermatology. - : Wiley. - 1600-0625 .- 0906-6705. ; 18:2, s. 109-15
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Tidskriftsartikel (refereegranskat)abstract
- A susceptibility locus for psoriasis, PSORS4, has been mapped to chromosome 1q21 in the region of the epidermal differentiation complex. The region has been refined to a 115 kb interval around the loricrin (LOR) gene. However, no evidence of association between polymorphisms in the LOR gene and psoriasis has been found. Therefore, we have analysed association to three candidate gene clusters of the region, the S100, small proline-rich protein (SPRR) and PGLYRP (peptidoglycan recognition protein) genes, which all contain functionally interesting psoriasis candidate genes. In previous studies, the SPRR and S100 genes have shown altered expression in psoriasis. Also polymorphisms in the PGLYRP genes have shown to be associated with psoriasis. We genotyped altogether 29 single nucleotide polymorphisms (SNPs) in 255 Finnish psoriasis families and analysed association with psoriasis using transmission disequilibrium test. A five-SNP haplotype of PGLYRP SNPs associated significantly with psoriasis. There was also suggestive evidence of association to SPRR gene locus in Finnish families. To confirm the putative associations, selected SNPs were genotyped also in a family collection of Swedish and Irish patients. The families supported association to the two gene regions, but there was also evidence of allelic heterogeneity.
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