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Sökning: WFRF:(Bruhn Sören) > (2020-2021)

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1.
  • Acevedo, Nathalie, et al. (författare)
  • DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:2
  • Tidskriftsartikel (refereegranskat)abstract
    • DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p <= 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.
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2.
  • Acevedo, Nathalie, et al. (författare)
  • Epigenetic alterations in skin homing CD4(+)CLA(+) T cells of atopic dermatitis patients
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations -(CD4(+), -CD4(+)CD45RA(+) naive, -CD4(+)CLA(+), and -CD8(+)) from adult AD patients and healthy controls (HC). Skin homing -CD4(+)CLA(+) T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in -CD4(+)CLA(+) T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in -CD4(+)CLA(+) T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing -CD4(+)CLA(+) T cells and uncover putative molecules participating in AD pathways.
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3.
  • Juul, Louise, et al. (författare)
  • Ulva fenestrata protein – comparison of three extraction methods with respect to protein yield and protein quality
  • 2021
  • Ingår i: Algal Research. - : Elsevier BV. - 2211-9264. ; 60
  • Tidskriftsartikel (refereegranskat)abstract
    • Seaweed is gaining attention as a possible alternative and sustainable source of proteins. This study investigates three protein extraction methods and their effect on protein yield and quality when applied to Ulva fenestrata . Two of the methods included alkaline extractions (pH-shifts); one version solubilizing the proteins at pH 8.5 and one solubilizing them at pH 8.5 followed by pH 12 (pH 8.5+12). The third method was a mechanical pressing, using a double screw press. All extraction methods were followed by isoelectric precipitation to concentrate the proteins. Extraction at pH 8.5 gave the significantly highest total protein yield after the isoelectric precipitation, followed by extraction at pH 8.5+12 and lastly mechanical extraction gave the lowest yield. Proteins extracted with both alkaline methods had a significantly higher solubility at pH 7 and pH 9, compared to proteins from the mechanical pressing. There were no significant differences between the three methods in total D/L-amino acid ratio. Amino acid cross-links measured as lysinoalanine (LAL) and lanthionine (LAN) where found in significantly higher amounts in alkali-extracted proteins compared to mechanically extracted, however not to a degree that expect to compromise functional or nutritional quality. Further, no significant difference in protein in vitro digestibility was found between extraction methods. In conclusion, results indicated that protein extraction at pH 8.5 can be recommended, especially regarding total protein yield and solubility of the final protein extract.
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