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  • 1.
    Alijagic, Andi
    et al.
    Örebro University, School of Science and Technology. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Kotlyar, Oleksandr
    Örebro University, School of Science and Technology.
    Karlsson, Patrik
    Örebro University, School of Science and Technology.
    Wang, Xuying
    KTH Royal Institute of Technology, Department of Chemistry, Division of Surface and Corrosion Science, SE-100 44 Stockholm, Sweden.
    Odnevall, Inger
    KTH Royal Institute of Technology, Department of Chemistry, Division of Surface and Corrosion Science, SE-100 44 Stockholm, Sweden; AIMES-Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Benada, Oldřich
    Institute of Microbiology of the Czech Academy of Sciences, 140 00 Prague, Czech Republic.
    Amiryousefi, Ali
    Örebro University, School of Medical Sciences.
    Andersson, Lena
    Örebro University, School of Medical Sciences. Örebro University Hospital. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden; Department of Occupational and Environmental Medicine, Örebro University Hospital, Örebro, Sweden.
    Persson, Alexander
    Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden .
    Felth, Jenny
    Uddeholms AB, SE-683 85 Hagfors, Sweden.
    Andersson, Henrik
    Uddeholms AB, SE-683 85 Hagfors, Sweden.
    Larsson, Maria
    Örebro University, School of Science and Technology.
    Hedbrant, Alexander
    Örebro University, School of Medical Sciences. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
    Salihovic, Samira
    Örebro University, School of Medical Sciences. Man-Technology-Environment Research Center (MTM), Örebro University, SE-701 82 Örebro, Sweden; Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
    Engwall, Magnus
    Örebro University, School of Science and Technology.
    A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles2023In: Cells, E-ISSN 2073-4409, Vol. 12, no 2, article id 281Article in journal (Refereed)
    Abstract [en]

    Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

  • 2.
    Andersson, Erik
    et al.
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    D'Amato, M.
    Department of Medicine, Karolinska Institutet Solna, Stockholm, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Inflammatory biomarkers in serum discriminate Crohn's disease and ulcerative colitis from healthy controls2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no Suppl. 1, p. S86-S87Article in journal (Other academic)
  • 3.
    Andersson, Erik
    et al.
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Neumann, Gunter
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE Basque Foundation for Science, Bilbao, Spain.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186142Article in journal (Refereed)
    Abstract [en]

    Objective: Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay.

    Methods: A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort.

    Results: By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort.

    Conclusions: By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.

  • 4. Andorf, Sandra
    et al.
    Altmann, T
    Witucka-Wall, H
    Selbig, Joachim
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Molecular network structures in heterozygotes: A systems-biology approach to heterosis2009Conference paper (Refereed)
  • 5.
    Andorf, Sandra
    et al.
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Gärtner, Tanja
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Steinfath, Matthias
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Witucka-Wall, Hanna
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Altmann, Thomas
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Towards systems biology of heterosis: a hypothesis about molecular network structure applied for the Arabidopsis metabolome2009In: EURASIP Journal on Bioinformatics and Systems Biology, ISSN 1687-4145, E-ISSN 1687-4153, article id 147157Article in journal (Refereed)
    Abstract [en]

    We propose a network structure-based model for heterosis, and investigate it relying on metabolite profiles from Arabidopsis. A simple feed-forward two-layer network model (the Steinbuch matrix) is used in our conceptual approach. It allows for directly relating structural network properties with biological function. Interpreting heterosis as increased adaptability, our model predicts that the biological networks involved show increasing connectivity of regulatory interactions. A detailed analysis of metabolite profile data reveals that the increasing-connectivity prediction is true for graphical Gaussian models in our data from early development. This mirrors properties of observed heterotic Arabidopsis phenotypes. Furthermore, the model predicts a limit for increasing hybrid vigor with increasing heterozygosity--a known phenomenon in the literature.

  • 6.
    Andorf, Sandra
    et al.
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Department of Medicine, Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.
    Meyer, Rhonda C
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Selbig, Joachim
    Bioinformatics Chair, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
    Altmann, Thomas
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Repsilber, Dirk
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Integration of a systems biological network analysis and QTL results for biomass heterosis in Arabidopsis thaliana2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 11, article id e49951Article in journal (Refereed)
    Abstract [en]

    To contribute to a further insight into heterosis we applied an integrative analysis to a systems biological network approach and a quantitative genetics analysis towards biomass heterosis in early Arabidopsis thaliana development. The study was performed on the parental accessions C24 and Col-0 and the reciprocal crosses. In an over-representation analysis it was tested if the overlap between the resulting gene lists of the two approaches is significantly larger than expected by chance. Top ranked genes in the results list of the systems biological analysis were significantly over-represented in the heterotic QTL candidate regions for either hybrid as well as regarding mid-parent and best-parent heterosis. This suggests that not only a few but rather several genes that influence biomass heterosis are located within each heterotic QTL region. Furthermore, the overlapping resulting genes of the two integrated approaches were particularly enriched in biomass related pathways. A chromosome-wise over-representation analysis gave rise to the hypothesis that chromosomes number 2 and 4 probably carry a majority of the genes involved in biomass heterosis in the early development of Arabidopsis thaliana.

  • 7. Andorf, Sandra
    et al.
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Molecular network structures in heterozygotes: A systems biological approach to heterosis2009In: Neue Methoden der Biometrie: 55. Biometrisches Kolloquium / [ed] R. Foraita, T. Gerds, L. A. Hothorn, M. Kieser, O. Kuß, U. Munzel, R. Vonk, A. Ziegler, 2009Conference paper (Refereed)
  • 8.
    Andorf, Sandra
    et al.
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
    Selbig, Joachim
    University of Potsdam, Potsdam-Golm, Germany.
    Altmann, T
    Leibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany.
    Witucka-Wall, H
    University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Gremany.
    Heterosis in Arabidopsis thaliana: A metabolite network structure approach2010In: 11th Day of the Doktoral Student: abstract; 19 May 2010, Dummerstorf, Dummerstorf, Germany: FBN , 2010, p. 7-10Conference paper (Refereed)
  • 9.
    Andorf, Sandra
    et al.
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Selbig, Joachim
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Altmann, Thomas
    Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Poos, Kathrin
    University of Applied Sciences Gelsenkirchen Site Recklinghausen, Recklinghausen, Germany .
    Witucka-Wall, Hanna
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Enriched partial correlations in genome-wide gene expression profiles of hybrids (A. thaliana): a systems biological approach towards the molecular basis of heterosis2010In: Theoretical and Applied Genetics, ISSN 0040-5752, E-ISSN 1432-2242, Vol. 120, no 2, p. 249-59Article in journal (Refereed)
    Abstract [en]

    Heterosis is a well-known phenomenon but the underlying molecular mechanisms are not yet established. To contribute to the understanding of heterosis at the molecular level, we analyzed genome-wide gene expression profile data of Arabidopsis thaliana in a systems biological approach. We used partial correlations to estimate the global interaction structure of regulatory networks. Our hypothesis states that heterosis comes with an increased number of partial correlations which we interpret as increased numbers of regulatory interactions leading to enlarged adaptability of the hybrids. This hypothesis is true for mid-parent heterosis for our dataset of gene expression in two homozygous parental lines and their reciprocal crosses. For the case of best-parent heterosis just one hybrid is significant regarding our hypothesis based on a resampling analysis. Summarizing, both metabolome and gene expression level of our illustrative dataset support our proposal of a systems biological approach towards a molecular basis of heterosis.

  • 10. Andorf, Sandra
    et al.
    Selbig, Joachim
    Meyer, Rhonda
    Altmann, Thomas
    Repsilber, Dirk
    Integrating a molecular network hypothesis and QTL results for heterosis in Arabidopsis thaliana2010In: Statistical Computings 2010: Abstracts der 42. Arbeitstagung, 2010, Vol. 5Conference paper (Refereed)
  • 11.
    Bachmann, Radu
    et al.
    Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, Brussels, Belgium; Colorectal Surgery Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
    Van Hul, Matthias
    Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, Brussels, Belgium.
    Baldin, Pamela
    Pathology Department, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
    Léonard, Daniel
    Colorectal Surgery Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
    Delzenne, Nathalie M.
    Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, Brussels, Belgium.
    Belzer, Clara
    Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
    Ouwerkerk, Janneke P.
    Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Kartheuser, Alex
    Colorectal Surgery Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    De Vos, Willem M.
    Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands; Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Cani, Patrice D.
    Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, Brussels, Belgium.
    Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism2022In: Cells, E-ISSN 2073-4409, Vol. 11, no 17, article id 2666Article in journal (Refereed)
    Abstract [en]

    Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.

  • 12.
    Baxter, Charles J
    et al.
    Department of Plant Sciences, University of Oxford, Oxford, United Kingdom.
    Redestig, Henning
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Schauer, Nicolas
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Repsilber, Dirk
    ax-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Patil, Kiran R
    Center for Microbial Biotechnology, BioCentrum Technical University of Denmark, Kongens Lyngby, Denmark.
    Nielsen, Jens
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Selbig, Joachim
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Liu, Junli
    Genetics Programme, Scottish Crop Research Institute, Dundee, United Kingdom .
    Fernie, Alisdair R
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Sweetlove, Lee J
    Department of Plant Sciences, University of Oxford, Oxford, United Kingdom.
    The metabolic response of heterotrophic Arabidopsis cells to oxidative stress2007In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 143, no 1, p. 312-25Article in journal (Refereed)
    Abstract [en]

    To cope with oxidative stress, the metabolic network of plant cells must be reconfigured either to bypass damaged enzymes or to support adaptive responses. To characterize the dynamics of metabolic change during oxidative stress, heterotrophic Arabidopsis (Arabidopsis thaliana) cells were treated with menadione and changes in metabolite abundance and (13)C-labeling kinetics were quantified in a time series of samples taken over a 6 h period. Oxidative stress had a profound effect on the central metabolic pathways with extensive metabolic inhibition radiating from the tricarboxylic acid cycle and including large sectors of amino acid metabolism. Sequential accumulation of metabolites in specific pathways indicated a subsequent backing up of glycolysis and a diversion of carbon into the oxidative pentose phosphate pathway. Microarray analysis revealed a coordinated transcriptomic response that represents an emergency coping strategy allowing the cell to survive the metabolic hiatus. Rather than attempt to replace inhibited enzymes, transcripts encoding these enzymes are in fact down-regulated while an antioxidant defense response is mounted. In addition, a major switch from anabolic to catabolic metabolism is signaled. Metabolism is also reconfigured to bypass damaged steps (e.g. induction of an external NADH dehydrogenase of the mitochondrial respiratory chain). The overall metabolic response of Arabidopsis cells to oxidative stress is remarkably similar to the superoxide and hydrogen peroxide stimulons of bacteria and yeast (Saccharomyces cerevisiae), suggesting that the stress regulatory and signaling pathways of plants and microbes may share common elements.

  • 13.
    Bazov, Igor
    et al.
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Hedin, C. R.
    Karolinska Institutet, Department of Medicine, Solna, Stockholm, Sweden; Karolinska University Hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Carlson, M.
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    van Nieuwenhoven, Michiel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Keita, Å. V.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Magnusson, M. K.
    University of Gothenburg, Sahlgrenska Academy, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden.
    Almer, S.
    Karolinska Institutet, Department of Medicine, Solna, Stockholm, Sweden; Karolinska university hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Strid, H.
    Södra Älvsborgs Hospital, Department of Internal Medicine, Borås, Sweden.
    Mathisen, C. Bache-Wiig
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Bengtsson, M. B.
    Vestfold Hospital Trust, Department of Gastroenterology, Tønsberg, Norway.
    Aabrekk, T. Bergene
    University of Oslo, Institute of Clinical Medicine, Oslo, Norway; Vestfold Hospital Trust, Department of Gastroenterology, Tønsberg, Norway.
    Medhus, A. W.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Detlie, T. E.
    Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway; University of Oslo, Insititute of Clinical Medicine, Oslo, Norway.
    Frigstad, S. O.
    Vestre Viken Hospital Trust- Bærum Hospital, Department of Internal Medicine, Bærum, Norway.
    Huppertz-Hauss, G.
    Telemark Hospital Trust, Skien, Department of Gastroenterology, Skien, Norway.
    Opheim, R.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Health and Society, Oslo, Norway.
    Ricanek, P.
    Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway; Lovisenberg Diaconal Hospital, Department of Gastroenterology, Oslo, Norway.
    Kristensen, V. A.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway .
    Salihovic, Samira
    Örebro University, School of Medical Sciences.
    D'Amato, M.
    Karolinska Institutet, Clinical Epidemiology Division, Department of Medicine Solna, Stockholm, Sweden; IKERBASQUE, Basque Foundation for Science, Bilbao, Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Bilbao, Spain.
    Öhman, L.
    University of Gothenburg, Sahlgrenska Academy, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden.
    Söderholm, J. D.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Lindqvist, C. M.
    Örebro University, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Høivik, M. L.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I314-I315, article id P154Article in journal (Other academic)
  • 14.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Andersson, Erik
    Örebro University, School of Medical Sciences. Department of Gastroenterolog.
    Hultdin, Johan
    Department of Medical Biosciences, Division of Clinical Chemistry, Umeå University, Umeå, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Rush, Stephen T.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kalla, Rahul
    MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Adams, Alex T.
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
    Keita, Åsa V.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    D'Amato, Mauro
    CIC bioGUNE Basque Research and Technology Alliance, BRTA and IKERBASQUE, Basque Science Foundation, Bilbao, Spain; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Gomollon, Fernando
    HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain.
    Jahnsen, Jorgen
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Ricanek, Petr
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
    Satsangi, Jack
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Systemic Inflammation in Preclinical Ulcerative Colitis2021In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, no 5, p. 1526-1539.e9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Pre-clinical ulcerative colitis is poorly defined. We aimed to characterize the pre-clinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.

    METHODS: We obtained plasma samples, biobanked from individuals who later in life developed ulcerative colitis (n=72), and matched healthy controls (n=140), within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biological relevance of these findings were validated in an inception cohort of ulcerative colitis patients (n=101), and healthy controls (n=50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of ulcerative colitis patients (n=41) and matched healthy controls (n=37) were explored.

    RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP1) were upregulated (p<0.05) in pre-clinical ulcerative colitis compared to controls based on both univariate and mulativariable models. Ingenuity Pathway Analyses identified several potential key regulators, including IL-1b, TNF, IFN-gamma, OSM, NFĸB, IL-6 and IL-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve ulcerative colitis patients from controls with leave-one-out cross-validation (AUC=0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly upregulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.

    CONCLUSIONS: A set of inflammatory proteins are upregulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be upregulated already at exposure to genetic and environmental risk factors.

  • 15.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences.
    Andersson, Erik
    Örebro University, School of Medical Sciences.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Division of Medicine, Umea University, Umeå, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hultdin, Johan
    Medical Biosciences, Clinical Chemistry, Umea University, Umeå, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    IBD Character Consortium,
    Markers of systemic inflammation in preclinical ulcerative colitis2019In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 7, no 8_suppl, p. 111-111Article in journal (Refereed)
    Abstract [en]

    Introduction: Data on the preclinical stage of ulcerative colitis (UC) are sparse. At diagnosis, UC often shows a modest increase in systemic inflammatory markers like C-reactive protein (CRP). However, a subclinical inflammation with elevated levels of CRP and interleukin-6 (IL6) in serum have been observed several years before diagnosis [1]. First-degree relatives, including healthy twin siblings, also display elevated levels of some inflammatory markers as a consequence of shared genetic and environmental risk factors [2]. It is reasonable to believe that the preclinical inflammation, reflecting early pathogenic mechanisms, ultimately leads to a diagnosis of UC.

    Aim and Method: We aimed to deeper examine the systemic preclinical inflammation in UC using a comprehensive set of protein markers. Cases with UC were identified at clinical follow-up of a prospectively collected population-based cohort of healthy individuals from northern Sweden. Plasma samples from cases and controls were subjected to proximity extension assay for relative quantification of 92 protein markers of inflammation. Results were validated in an inception cohort of treatment naïve, newly diagnosed patients with UC (n=101) vs. healthy controls (n=50). In addition, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of twins with UC (n=41) and matched healthy controls (n=37) were explored.

    Results: Pre-diagnostic plasma samples from 72 cases who later in life developed UC and 140 controls, matched for gender, age, year of health survey and area of residence, were identified (table 1). Six proteins were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. A receiver-operating curve based prediction model using the six protein markers combined with sex, age, smoking status and time to diagnose was set up for validation. The model discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings vs. healthy controls and four out of six proteins were upregulated similarly as in the pre-diagnostic samples. The relative levels of the six proteins showed an intermediate upregulation in pre-diagnostic samples and samples from healthy twin siblings compared to samples at diagnosis of UC. Only one protein showed a significant correlation with time to diagnosis in the pre-diagnostic samples. Using pathway analysis, the six protein upregulations pointed towards subclinical inflammation in UC being caused by dysregulation of four immune pathways.

    Conclusions: This is the first comprehensive characterisation of preclinical systemic inflammation in UC. Inflammatory proteins were upregulated several years prior to diagnosis of UC and to some extent these alterations were also seen in healthy twin siblings of UC patients. Characterisation of the preclinical stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.

  • 16.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Seifert, M.
    Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Engstrand, L.
    Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Increasing abundance of faecalibacterium prausnitzii is associated with decreased intestinal inflammation in Crohn's disease: A longitudinal study2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S468-S469Article in journal (Other academic)
  • 17.
    Brand, Bodo
    et al.
    Research Group of Functional Genomics, Leibniz Institute of Farm Animal Biology, Dummerstorf, Germany .
    Hartmann, Anja
    Research Group of Functional Genomics, Leibniz Institute of Farm Animal Biology, Dummerstorf, Germany .
    Repsilber, Dirk
    Research Unit of Genetics and Biometry, Leibniz Institute of Farm Animal Biology, Dummerstorf, Germany .
    Griesbeck-Zilch, Bettina
    Institute of Physiology, Technical University Munich, Freising, Germany.
    Wellnitz, Olga
    Veterinary Physiology, Vetsuisse Faculty, University of Bern, Posieux, Switzerland .
    Kühn, Christa
    Research Unit of Molecular Biology, Leibniz Institute of Farm Animal Biology, Dummerstorf, Germany.
    Ponsuksili, Siriluck
    Research Group of Functional Genomics, Leibniz Institute of Farm Animal Biology, Dummerstorf, Germany .
    Meyer, Heinrich H D
    Institute of Physiology, Technical University Munich, Freising, Germany.
    Schwerin, Manfred
    Research Group of Functional Genomics, Leibniz Institute of Farm Animal Biology, Dummerstorf, Germany; Institute of Farm Animal Science and Technology, University of Rostock, Rostock, Germany .
    Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score2011In: Genetics Selection Evolution, ISSN 0999-193X, E-ISSN 1297-9686, Vol. 43, no 1, article id 24Article in journal (Refereed)
    Abstract [en]

    Background: During the past ten years many quantitative trait loci (QTL) affecting mastitis incidence and mastitis related traits like somatic cell score (SCS) were identified in cattle. However, little is known about the molecular architecture of QTL affecting mastitis susceptibility and the underlying physiological mechanisms and genes causing mastitis susceptibility. Here, a genome-wide expression analysis was conducted to analyze molecular mechanisms of mastitis susceptibility that are affected by a specific QTL for SCS on Bos taurus autosome 18 (BTA18). Thereby, some first insights were sought into the genetically determined mechanisms of mammary gland epithelial cells influencing the course of infection.

    Methods: Primary bovine mammary gland epithelial cells (pbMEC) were sampled from the udder parenchyma of cows selected for high and low mastitis susceptibility by applying a marker-assisted selection strategy considering QTL and molecular marker information of a confirmed QTL for SCS in the telomeric region of BTA18. The cells were cultured and subsequently inoculated with heat-inactivated mastitis pathogens Escherichia coli and Staphylococcus aureus, respectively. After 1, 6 and 24 h, the cells were harvested and analyzed using the microarray expression chip technology to identify differences in mRNA expression profiles attributed to genetic predisposition, inoculation and cell culture.

    Results: Comparative analysis of co-expression profiles clearly showed a faster and stronger response after pathogen challenge in pbMEC from less susceptible animals that inherited the favorable QTL allele 'Q' than in pbMEC from more susceptible animals that inherited the unfavorable QTL allele 'q'. Furthermore, the results highlighted RELB as a functional and positional candidate gene and related non-canonical Nf-kappaB signaling as a functional mechanism affected by the QTL. However, in both groups, inoculation resulted in up-regulation of genes associated with the Ingenuity pathways 'dendritic cell maturation' and 'acute phase response signaling', whereas cell culture affected biological processes involved in 'cellular development'.

    Conclusions: The results indicate that the complex expression profiling of pathogen challenged pbMEC sampled from cows inheriting alternative QTL alleles is suitable to study genetically determined molecular mechanisms of mastitis susceptibility in mammary epithelial cells in vitro and to highlight the most likely functional pathways and candidate genes underlying the QTL effect.

  • 18.
    Carstens, Adam
    et al.
    Örebro University, School of Medical Sciences. Department of Internal Medicine, Ersta Hospital, Stockholm, Sweden; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Björkqvist, Olle
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Rangel, I.
    Department of Internal Medicine, Ersta Hospital, Stockholm, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Bresso, F.
    Division of Gastroenterology, Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
    Strid, H.
    Department of Internal Medicine, Södra Älvsborgs Hospital, Borås, Sweden.
    Hjortswang, H.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Keita, Å.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Magnusson, M. K.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Hedin, C.
    Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden; Karolinska University Hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Engstrand, L.
    Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna, Sweden.
    Carlson, M.
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Söderholm, J.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Surgery, Linköping University, Linköping, Sweden.
    Öhman, L.
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Gut microbiota associated with treatment outcome to biological treatment in inflammatory bowel diseaseManuscript (preprint) (Other academic)
  • 19.
    Chavan, Swapnil
    et al.
    School of Science and Technology, Örebro University, Örebro, Sweden.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Engwall, Magnus
    Örebro University, School of Science and Technology.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Predicting Chemical-Induced Liver Toxicity Using High-Content Imaging Phenotypes and Chemical Descriptors: A Random Forest Approach2020In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 33, no 9, p. 2261-2275Article in journal (Refereed)
    Abstract [en]

    Hepatotoxicity is a major reason for the withdrawal or discontinuation of drugs from clinical trials. Thus, better tools are needed to filter potential hepatotoxic drugs early in drug discovery. Our study demonstrates utilization of HCI phenotypes, chemical descriptors, and both combined (hybrid) descriptors to construct random forest classifiers (RFCs) for the prediction of hepatotoxicity. HCI data published by Broad Institute provided HCI phenotypes for about 30 000 samples in multiple replicates. Phenotypes belonging to 346 chemicals, which were tested in up to eight replicates, were chosen as a basis for our analysis. We then constructed individual RFC models for HCI phenotypes, chemical descriptors, and hybrid (chemical and HCI) descriptors. The model that was constructed using selective hybrid descriptors showed high predictive performance with 5-fold cross validation (CV) balanced accuracy (BA) at 0.71, whereas within the given applicability domain (AD), independent test set and external test set prediction BAs were equal to 0.61 and 0.60, respectively. The model constructed using chemical descriptors showed a similar predictive performance with a 5-fold CV BA equal to 0.66, a test set prediction BA within the AD equal to 0.56, and an external test set prediction BA within the AD equal to 0.50. In conclusion, the hybrid and chemical descriptor-based models presented here should be considered as a new tool for filtering hepatotoxic molecules during compound prioritization in drug discovery.

  • 20.
    Degenkolbe, Thomas
    et al.
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany .
    Do, Phuc Thi
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany .
    Zuther, Ellen
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany .
    Repsilber, Dirk
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany; Forschungsinstitut für Die Biologie Landwirtschaftlicher Nutztiere (FBN), Dummerstorf, Germany.
    Walther, Dirk
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany .
    Hincha, Dirk K
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany .
    Köhl, Karin I
    Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam, Germany .
    Expression profiling of rice cultivars differing in their tolerance to long-term drought stress2009In: Plant Molecular Biology, ISSN 0167-4412, E-ISSN 1573-5028, Vol. 69, no 1-2, p. 133-53Article in journal (Refereed)
    Abstract [en]

    Understanding the molecular basis of plant performance under water-limiting conditions will help to breed crop plants with a lower water demand. We investigated the physiological and gene expression response of drought-tolerant (IR57311 and LC-93-4) and drought-sensitive (Nipponbare and Taipei 309) rice (Oryza sativa L.) cultivars to 18 days of drought stress in climate chamber experiments. Drought stressed plants grew significantly slower than the controls. Gene expression profiles were measured in leaf samples with the 20 K NSF oligonucleotide microarray. A linear model was fitted to the data to identify genes that were significantly regulated under drought stress. In all drought stressed cultivars, 245 genes were significantly repressed and 413 genes induced. Genes differing in their expression pattern under drought stress between tolerant and sensitive cultivars were identified by the genotype x environment (G x E) interaction term. More genes were significantly drought regulated in the sensitive than in the tolerant cultivars. Localizing all expressed genes on the rice genome map, we checked which genes with a significant G x E interaction co-localized with published quantitative trait loci regions for drought tolerance. These genes are more likely to be important for drought tolerance in an agricultural environment. To identify the metabolic processes with a significant G x E effect, we adapted the analysis software MapMan for rice. We found a drought stress induced shift toward senescence related degradation processes that was more pronounced in the sensitive than in the tolerant cultivars. In spite of higher growth rates and water use, more photosynthesis related genes were down-regulated in the tolerant than in the sensitive cultivars.

  • 21.
    Djekic, Demir
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Pinto, Rui
    Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Henein, Michael
    Department of Public Health and Clinical Medicine, Umeå University and Heart Centre, Umeå, Sweden; Molecular and Clinic Research Institute, St George University, London, UK; Institute of Environment, Health and Physical Sciences, Brunel University, London, UK.
    Serum untargeted lipidomic profiling reveals dysfunction of phospholipid metabolism in subclinical coronary artery disease2019In: Vascular Health and Risk Management, ISSN 1176-6344, E-ISSN 1178-2048, Vol. 15, p. 123-135Article in journal (Refereed)
    Abstract [en]

    Purpose: Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates.

    Patients and methods: We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1-250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients' serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach.

    Results: We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG (49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC.

    Conclusion: In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.

  • 22.
    Drobin, Kimi
    et al.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Assadi, Ghazaleh
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Hong, Mun-Gwan
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Andersson, Eni
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Fredolini, Claudia
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Forsström, Björn
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Reznichenko, Anna
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Akhter, Tahmina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Ek, Weronica E.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain.
    Hansen, Mark Berner
    AstraZeneca R&D Mölndal, Innovative and Global Medicines, Mölndal, Sweden; Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
    Sandberg, Kristian
    Science for Life Laboratory, Drug Discovery & Development Platform & Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Greco, Dario
    Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Schwenk, Jochen M.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed)
    Abstract [en]

    Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.

    Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.

    Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.

    Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

  • 23.
    Edebol Carlman, Hanna M. T.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Department of Radiology and Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology. Center for Applied Autonomous Sensor Systems.
    Pruessner, Jens C.
    Douglas Institute, McGill University, Montréal, QC H4H1R3, Canada; Department of Psychology, University of Konstanz, Konstanz, Germany.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study2022In: Nutrients, E-ISSN 2072-6643, Vol. 14, no 7, article id 1329Article in journal (Refereed)
    Abstract [en]

    Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.

  • 24.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Ljotsson, Brjann
    Department of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
    Linton, Steven J.
    Örebro University, School of Law, Psychology and Social Work.
    Boersma, Katja
    Schrooten, Martien
    Örebro University, School of Law, Psychology and Social Work.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Brummer, Robert J.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre.
    Face-to-Face Cognitive-Behavioral Therapy for Irritable Bowel Syndrome: The Effects on Gastrointestinal and Psychiatric Symptoms2017In: Gastroenterology Research and Practice, ISSN 1687-6121, E-ISSN 1687-630X, article id 8915872Article in journal (Refereed)
    Abstract [en]

    Irritable bowel syndrome (IBS) is a gastrointestinal disorder linked to disturbances in the gut-brain axis. Visceral hypersensitivity and pain are hallmarks of IBS and linked to the physiological and psychological burden and to the nonadaptive coping with stress. Cognitive-behavioral therapy (CBT) for IBS has proven effective in reducing gastrointestinal and psychiatric symptoms in IBS by means of coping with stress. The present pilot study evaluated for the first time whether CBT for IBS affected visceral sensitivity and pain. Individual CBT was performed for 12 weeks in 18 subjects with IBS and evaluated in terms of visceral sensitivity and pain during rectal distensions using the barostat method and self-rated visceral sensitivity and gastrointestinal and psychiatric symptoms. Visceral discomfort, urge, and pain induced by the barostat were not affected by CBT but were stable across the study. However, the level of self-rated visceral sensitivity and gastrointestinal and psychiatric symptoms decreased after the intervention. Central working mechanisms and increased ability to cope with IBS-symptoms are suggested to play a key role in the alleviation of IBS symptoms produced by CBT.

  • 25.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Thunberg, Per
    Örebro University, School of Medical Sciences.
    Lathrop Stern, Lori
    Labus, Jennifer
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Evaluating the effects of probiotic intake on brain activity during an emotional attention task and blood markers related to stress in healthy subjects2019Conference paper (Refereed)
  • 26.
    Edebol-Carlman, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Rode, Julia
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hutchinson, Ashley N.
    Örebro University, School of Medical Sciences.
    Thunberg, Per
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Physics.
    Persson, Jonas
    Örebro University, School of Law, Psychology and Social Work.
    Kiselev, Andrey
    Örebro University, School of Science and Technology.
    Pruessner, Jens C.
    McGill Centre for Studies in Ageing, Department of Psychology, Psychiatry, Neurology and Neurosurgery, Douglas Institute, McGill University, Montréal, Canada.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Probiotic mixture containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum affects brain responses to an arithmetic stress task in healthy subjects: A randomized clinical trialManuscript (preprint) (Other academic)
  • 27.
    Engelheart, Stina
    et al.
    Örebro University, School of Medical Sciences.
    Andrén, Daniela
    Örebro University, Örebro University School of Business.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Bertéus Forslund, Heléne
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Nutritional status in older people: an explorative analysisManuscript (preprint) (Other academic)
  • 28.
    Engelheart, Stina
    et al.
    Örebro University, School of Medical Sciences.
    Andrén, Daniela
    Örebro University, Örebro University School of Business.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Bertéus Forslund, Heléne
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Nutritional status in older people: An explorative analysis2021In: Clinical Nutrition ESPEN, E-ISSN 2405-4577, Vol. 46, p. 424-433Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: The nutritional status is seldom defined in general, but is considered to be important throughout life span, especially in times of diseases and disabilities. We previously proposed a theoretical model of the nutritional status from a functional perspective [1], however without proposing a definition of the nutritional status. The model comprises four domains that might affect the nutritional and functional status in a bidirectional way. These four domains are: Food and nutrition; Health and somatic disorders; Physical function and capacity; and Cognitive, affective, and sensory function. This study contributes to the existing literature and knowledge by empirically analysing patterns and relationships of possible nutritional status indicators within and between the four domains.

    METHODS: This study is based on a sample of 69 men and women; older than 65 years, receiving home health care. They were followed up for three years. A broad set of nutritional status indicators in the participants were assessed in their home yearly. Given the small sample size and large number of variables, we used both correlation and factor analysis to explore patterns of nutritional status indicators within the four domains and relationships between the four domains suggested by the theoretical model of nutritional status which we proposed earlier.

    RESULTS: At baseline, between 4 and 18 components were extracted from the four domains, separately, using factor analysis. The first three components of each domain (called main components) were correlated (p < 0.05) with at least one of the main components of each of the other three domains (r = -0.34-0.79 at baseline, 0.38-0.74 at year 1, 0.40-0.77 at year 2 and 0.47-0.71 at year 3). At baseline, these main components explained, respectively, 31%, 52%, 57% and 63% of the sample variation in the four domains. This remained stable throughout all three years of follow up. In all four domains, there were statistically significant differences in prevalence of malnutrition, frailty, sarcopenia, and dehydration (all different inadequate nutritional status) between individuals' individual component scores.

    CONCLUSIONS: This study provides empirical evidence for the relationship between nutritional status indicators within and between the four domains suggested by our theoretical model of nutritional status. Components in all four domains were associated with inadequate nutritional status, highlighting that a wide perspective of the nutritional status assessment is necessary to be applied in clinical practice.

  • 29.
    Fart, Frida
    et al.
    Örebro University, School of Medical Sciences.
    Rajan, Sukithar K
    Örebro University, School of Medical Sciences.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Ganda Mall, John Peter
    Örebro University, School of Medical Sciences. Laboratory of Translational Mucosal Immunology, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
    Tingö, Lina
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Differences in Gut Microbiome Composition between Senior Orienteering Athletes and Community-Dwelling Older Adults2020In: Nutrients, E-ISSN 2072-6643, Vol. 12, no 9, article id E2610Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Gastrointestinal (GI) health is an important aspect of general health. Gastrointestinal symptoms are of specific importance for the elderly, an increasing group globally. Hence, promoting the elderly's health and especially gastrointestinal health is important. Gut microbiota can influence gastrointestinal health by modulation of the immune system and the gut-brain axis. Diverse gut microbiota have been shown to be beneficial; however, for the elderly, the gut microbiota is often less diverse. Nutrition and physical activity, in particular, are two components that have been suggested to influence composition or diversity.

    MATERIALS AND METHODS: In this study, we compared gut microbiota between two groups of elderly individuals: community-dwelling older adults and physically active senior orienteering athletes, where the latter group has less gastrointestinal symptoms and a reported better well-being. With this approach, we explored if certain gut microbiota were related to healthy ageing. The participant data and faecal samples were collected from these two groups and the microbiota was whole-genome sequenced and taxonomically classified with MetaPhlAn.

    RESULTS: unclassified, which have been associated with impaired GI health. We could not observe any difference between the groups in terms of Shannon diversity index. Interestingly, a subgroup of community-dwelling older adults showed an atypical microbiota profile as well as the parameters for gastrointestinal symptoms and well-being closer to senior orienteers.

    CONCLUSIONS: Our results suggest specific composition characteristics of healthy microbiota in the elderly, and show that certain components of nutrition as well as psychological distress are not as tightly connected with composition or diversity variation in faecal microbiota samples.

  • 30.
    Fioretos, Thoas
    et al.
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; fioretDepartment of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden; Clinical Genomics Lund, Science for Life Laboratory, Lund University, Lund, Sweden.
    Wirta, Valtteri
    Department of Microbiology, Tumor and Cell Biology, Clinical Genomics Stockholm, Science Life Laboratory, Karolinska Institutet, Solna, Sweden; Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; School of Engineering Sciences in Chemistry, Biotechnology and Health, Clinical Genomics Stockholm, Science Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
    Cavelier, Lucia
    Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
    Berglund, Eva
    Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Friedman, Mikaela
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Akhras, Michael
    Department of Microbiology, Tumor and Cell Biology, Clinical Genomics Stockholm, Science Life Laboratory, Karolinska Institutet, Solna, Sweden.
    Botling, Johan
    Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ehrencrona, Hans
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden; Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research, Karolinska Institutet, Solna, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Fagerqvist, Therese
    Innovation Partnership Office, Uppsala University, Uppsala, Sweden.
    Gisselsson, David
    Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden. 11 Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden.
    Gruvberger-Saal, Sofia
    Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden.
    Gyllensten, Ulf
    Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Heidenblad, Markus
    Clinical Genomics Lund, Science for Life Laboratory, Lund University, Lund, Sweden.
    Höglund, Kina
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Jacobsson, Bo
    Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Johansson, Maria
    Lund University Collaboration Office, Lund University, Lund, Sweden.
    Johansson, Åsa
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Soller, Maria Johansson
    Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Genetics, Karolinska University Hospital, Solna, Sweden .
    Landström, Maréne
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Larsson, Pär
    Department of Medical Biosciences, Umeå University, Umeå, Sweden; Clinical Genomics Umeå, Science for Life Laboratory, Umeå University, Umeå, Sweden.
    Levin, Lars-Åke
    Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Lindstrand, Anna
    Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Genetics, Karolinska University Hospital, Solna, Sweden .
    Lovmar, Lovisa
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Lyander, Anna
    Department of Microbiology, Tumor and Cell Biology, Clinical Genomics Stockholm, Science Life Laboratory, Karolinska Institutet, Solna, Sweden; School of Engineering Sciences in Chemistry, Biotechnology and Health, Clinical Genomics Stockholm, Science Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden .
    Melin, Malin
    Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Nordgren, Ann
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Genetics, Karolinska University Hospital, Solna, Sweden; Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Biomedicine, Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden .
    Nordmark, Gunnel
    Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.
    Mölling, Paula
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Pathology and Genetics.
    Palmqvist, Lars
    Institute of Biomedicine, Department of Laboratory Medicine, University of Gothenburg, Gothenburg, Sweden; Clinical Genomics Gothenburg, Science for Life Laboratory, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden .
    Palmqvist, Richard
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Sikora, Per
    Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden; Clinical Genomics Gothenburg, Science for Life Laboratory, University of Gothenburg, Gothenburg, Sweden; Bioinformatics Data Center, Core Facilities, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden .
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Pathology and Genetics.
    Söderkvist, Peter
    Division of Medical Genetics, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Clinical Genomics Linköping, Linköping University, Linköping, Sweden.
    Stranneheim, Henrik
    Department of Microbiology, Tumor and Cell Biology, Clinical Genomics Stockholm, Science Life Laboratory, Karolinska Institutet, Solna, Sweden; Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden .
    Strid, Tobias
    Clinical Genomics Linköping, Linköping University, Linköping, Sweden; Department of Clinical Pathology, Biological and Clinical Sciences, Linköping University, Linköping, Sweden.
    Wheelock, Craig E.
    Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.
    Wadelius, Mia
    Department of Medical Sciences, Clinical Pharmacogenomics, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Wedell, Anna
    Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden .
    Edsjö, Anders
    Department of Clinical Genetics, Pathology and Molecular Diagnostics, Office for Medical Services, Region Skåne, Lund, Sweden; Division of Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Rosenquist, Richard
    Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
    Implementing precision medicine in a regionally organized healthcare system in Sweden2022In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 28, no 10, p. 1980-1982Article in journal (Refereed)
  • 31.
    Franks, P. W.
    et al.
    Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston MA, USA.
    Melén, E.
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Friedman, M.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sundström, J.
    Department of Cardiology, Akademiska Sjukhuset, Uppsala, Sweden; George Institute for Global Health, Camperdown NSW, Australia; Medical Sciences, Uppsala University, Uppsala, Sweden.
    Kockum, I.
    Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Klareskog, L.
    Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Rheumatology, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, C.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bergen, S. E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Czene, K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Hägg, S.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Hall, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Oncology, Södersjukhuset, Stockholm.
    Johnell, K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Malarstig, A.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Pfizer, Worldwide Research and Development, Stockholm, Sweden.
    Catrina, A.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hagström, H.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.
    Benson, M.
    Department of Pediatrics, Linköpings Universitet, Linköping, Sweden; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
    Gustav Smith, J.
    Department of Cardiology and Wallenberg Center for Molecular Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden, Sweden.
    Gomez, M. F.
    Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Orho-Melander, M.
    Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Jacobsson, B.
    Division of Health Data and Digitalisation, Norwegian Institute of Public Health, Genetics and Bioinformatics, Oslo, Norway; Department of Obstetrics and Gynecology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Functional Bioinformatics.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Jern, C.
    Department of Clinical Genetics and Genomics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Laboratory Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Melin, B.
    Department of Radiation Sciences, Oncology, Umeå Universitet, Umeå, Sweden.
    Ohlsson, C.
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, CBAR, University of Gothenburg, Gothenburg, Sweden; Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fall, T.
    Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
    Rönnblom, L.
    Department of Medical Sciences, Rheumatology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Wadelius, M.
    Department of Medical Sciences, Clinical Pharmacogenomics &Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Nordmark, G.
    Department of Medical Sciences, Rheumatology & Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Johansson, Å.
    Institute for Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
    Rosenquist, R.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Sullivan, P. F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill NC, USA; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill NC, USA.
    Technological readiness and implementation of genomic-driven precision medicine for complex diseases2021In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 290, no 3, p. 602-620Article, review/survey (Refereed)
    Abstract [en]

    The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

  • 32.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Östlund-Lagerström, Lina
    Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Nutrition and Physical Activity Research Centre, Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Algilani, Samal
    Örebro University, School of Health Sciences.
    Rasoal, Dara
    Örebro University, School of Health Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    V. Keita, Åsa
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?2018In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, no 1, article id 75Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.

    METHODS: Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).

    RESULTS: Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.

    CONCLUSIONS: Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

  • 33.
    Gorreja, Frida
    et al.
    Örebro University, School of Medical Sciences.
    Rush, Stephen
    Örebro University, School of Medical Sciences.
    Marques, Tatiana M.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Baker, Adam
    Örebro University, School of Medical Sciences. Head of Discovery, Microbiome and Human Health, Christian Hansen, Danimark.
    Wall, Rebecca
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    The impacts of probiotics and prebiotics on the gut mucosa and immune system through targeting inflammation and intestinal barrier function2018Conference paper (Other academic)
  • 34.
    Graunke, K L
    et al.
    Research Unit Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Langbein, Jan
    Research Unit Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Research Unit Genetics and Biometry, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Schön, P C
    Research Unit Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Objectively measuring behaviour traits in an automated restraint-test for ungulates: towards making temperament measurable2012In: Journal of Agricultural Science, ISSN 0021-8596, Vol. 151, no 1, p. 141-149Article in journal (Refereed)
    Abstract [en]

    The personality of an animal is described by traits that cause consistent actions and reactions to environmental stimuli. An important part of personality is the reaction to unpleasant or uncontrollable situations. Methods described in the literature to measure personality in animals are often based on measuring or rating escape behaviour in these situations. In the methods described, human handlers are frequently part of the experiment or the animals’ personalities are scored by humans. Thus, these methods are at least partly subjective. In the current study, an appliance to measure objectively the escape behaviour of ungulates and their reluctance during an uncontrollable situation (restraint) with a rather simple and comprehensible methodology is presented using a force transducer with adequate peripheral equipment. While the animals were restrained, a tractive forcetime diagram describing escape behaviour was recorded and later analysed with software developed specifically. To evaluate this newly developed technical method, 24 three-month-old calves were restrained by being tethered for 30 min on a halter that was connected to the force transducer. From the tractive force-time diagram, tractive force, maximal tractive force and the number of pulls that the calves performed during 5-min intervals were calculated. The multivariate results were analysed with a k-means-algorithm (function ‘kcca’) and a hierarchical clustering (function ‘hclust’) included in R version 2.12.1. Both analyses revealed two clearly separated clusters including the same individuals in each analysis. The animals of cluster 1 showed a continuously higher reaction level than those of cluster 2 with a strong reaction in the beginning, a short decrease before increasing during the middle of the experiment and a final decrease at the end of the test. The animals of cluster 2 had a lower and quite steady reaction level throughout the experiment, although even here a slight increase during the middle of the experiment could be detected before a final decrease towards the end of the test was shown. There was no significant difference in weight between the two clusters. The results showed that this newly developed method was able to detect differences in the animals’ escape behaviour patterns and reluctance with the measured parameters.

  • 35.
    Graunke, K L
    et al.
    Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Nürnberg, Gerd
    Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Schön, P C
    Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Langbein, Jan
    Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Temperamentbeschreibung am Beispiel des Rinds: ein multidimensionaler Ansatz mit Originaldaten2012In: 13th Day of the Doctoral Student: abstracts, 24 May 2012 Dummerstorf, Dummerstorf: FBN , 2012, p. 39-42Conference paper (Refereed)
  • 36.
    Graunke, Katharina L
    et al.
    Ethology Unit, Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Faculty of Agricultural and Environmental Sciences (AUF), PHENOMICS office, University of Rostock, Rostock, Germany.
    Nürnberg, Gerd
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Puppe, Birger
    Ethology Unit, Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Faculty of Agricultural and Environmental Sciences (AUF), Behavioural Sciences, University of Rostock, Rostock, Germany.
    Langbein, Jan
    Ethology Unit, Institute of Behavioural Physiology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Describing temperament in an ungulate: a multidimensional approach2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 9, article id e74579Article in journal (Refereed)
    Abstract [en]

    Studies on animal temperament have often described temperament using a one-dimensional scale, whereas theoretical framework has recently suggested two or more dimensions using terms like "valence" or "arousal" to describe these dimensions. Yet, the valence or assessment of a situation is highly individual. The aim of this study was to provide support for the multidimensional framework with experimental data originating from an economically important species (Bos taurus). We tested 361 calves at 90 days post natum (dpn) in a novel-object test. Using a principal component analysis (PCA), we condensed numerous behaviours into fewer variables to describe temperament and correlated these variables with simultaneously measured heart rate variability (HRV) data. The PCA resulted in two behavioural dimensions (principal components, PC): novel-object-related (PC 1) and exploration-activity-related (PC 2). These PCs explained 58% of the variability in our data. The animals were distributed evenly within the two behavioural dimensions independent of their sex. Calves with different scores in these PCs differed significantly in HRV, and thus in the autonomous nervous system's activity. Based on these combined behavioural and physiological data we described four distinct temperament types resulting from two behavioural dimensions: "neophobic/fearful--alert", "interested--stressed", "subdued/uninterested--calm", and "neoophilic/outgoing--alert". Additionally, 38 calves were tested at 90 and 197 dpn. Using the same PCA-model, they correlated significantly in PC 1 and tended to correlate in PC 2 between the two test ages. Of these calves, 42% expressed a similar behaviour pattern in both dimensions and 47% in one. No differences in temperament scores were found between sexes or breeds. In conclusion, we described distinct temperament types in calves based on behavioural and physiological measures emphasising the benefits of a multidimensional approach.

  • 37.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine, Div. of Gastroenterol., Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Department of Medicine, Div of Gastroenterol, Örebro Univ Hosp, Örebro, Sweden; Fac of Med and Hlth, Örebro Univ, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medical Sciences. Department of Microbiology and Immunology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

    Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

    Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

    Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

  • 38.
    Göthlin Eremo, Anna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tina, Elisabet
    Örebro University Hospital, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Fransén, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Wegman, Pia
    Linköping University Hospital, Linköping, Sweden.
    Repsilber, Dirk
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, UK .
    Sollie, Tomas
    Örebro University Hospital, Örebro, Sweden.
    Wingren, Sten
    Örebro University, School of Medicine, Örebro University, Sweden.
    Gene expression profiles in breast tumors from tamoxifen treated patients with and without distant recurrenceManuscript (preprint) (Other academic)
  • 39.
    Günaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Helenius, Gisela
    Örebro University, School of Medical Sciences.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health Sciences.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patientsManuscript (preprint) (Other academic)
  • 40.
    Günther, Juliane
    et al.
    Research Institute for the Biology of Farm Animals (FBN), Molecular Biology Research Unit, Dummerstorf, Germany.
    Koczan, Dirk
    Institute for Immunology, Steinbeis Transfercenter for Proteome Analysis, Core Facility for Transcriptome Analysis, Rostock, Germany.
    Yang, Wei
    Research Institute for the Biology of Farm Animals (FBN), Molecular Biology Research Unit, Dummerstorf, Germany; Department of Anesthesiology, Duke University Medical Center, Durham, United States .
    Nürnberg, Gerd
    Research Institute for the Biology of Farm Animals (FBN), Molecular Biology Research Unit, Dummerstorf, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals (FBN), Molecular Biology Research Unit, Dummerstorf, Germany.
    Schuberth, Hans-Joachim
    University of Veterinary Medicine, Immunology Unit, Hannover, Germany.
    Park, Zaneta
    AgResearch, Palmerston North, New Zealand.
    Maqbool, Nauman
    AgResearch, Ruakura Research Centre in Hamilton, New Zealand.
    Molenaar, Adrian
    AgResearch, Ruakura Research Centre in Hamilton, New Zealand.
    Seyfert, Hans-Martin
    Research Institute for the Biology of Farm Animals (FBN), Molecular Biology Research Unit, Dummerstorf, Germany.
    Assessment of the immune capacity of mammary epithelial cells: comparison with mammary tissue after challenge with Escherichia coli2009In: Veterinary research (Print), ISSN 0928-4249, E-ISSN 1297-9716, Vol. 40, no 4, article id 31Article in journal (Refereed)
    Abstract [en]

    We examined the repertoire and extent of inflammation dependent gene regulation in a bovine mammary epithelial cell (MEC) model, to better understand the contribution of the MEC in the immune defence of the udder. We challenged primary cultures of MEC from cows with heat inactivated Escherichia coli pathogens and used Affymetrix DNA-microarrays to profile challenge related alterations in their transcriptome. Compared to acute mastitis, the most prominently activated genes comprise those encoding chemokines, interleukins, beta-defensins, serum amyloid A and haptoglobin. Hence, the MEC exert sentinel as well as effector functions of innate immune defence. E. coli stimulated a larger fraction of genes (30%) in the MEC belonging to the functional category Inflammatory Response than we recorded with the same microarrays during acute mastitis in the udder (17%). This observation underscores the exquisite immune capacity of MEC. To more closely examine the adequacy of immunological regulation in MEC, we compared the inflammation dependent regulation of factors contributing to the complement system between the udder versus the MEC. In the MEC we observed only up regulation of several complement factor-encoding genes. Mastitis, in contrast, in the udder strongly down regulates such genes encoding factors contributing to both, the classical pathway of complement activation and the Membrane Attack Complex, while the expression of factors contributing to the alternative pathway may be enhanced. This functionally polarized regulation of the complex complement pathway is not reflected in the MEC models.

  • 41.
    Hartmann, Anja
    et al.
    Research Group Functional Genomics.
    Nürnberg, Gerd
    Research Unit Genetics and Biometrics.
    Repsilber, Dirk
    Research Unit Genetics and Biometrics.
    Janczyk, Pawel
    Institute of Veterinary Anatomy, Department of Veterinary Medicine, Free University of Berlin, Berlin, Germany.
    Walz, Chrsitina
    Research Group Functional Genomics.
    Ponsuksili, Siriluck
    Research Group Functional Genomics.
    Souffrant, Wolfgang-Bernhard
    Research Unit Nutritional Physiology, »Oskar Kellner«, Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Schwerin, Manfred
    Research Group Functional Genomics; Institute of Farm Animal Sciences and Technology, University of Rostock, Rostock, Germany.
    Effects of threshold choice on the results of gene expression profiling, using microarray analysis, in a model feeding experiment with rat2009In: Archiv für Tierzucht, ISSN 0003-9438, Vol. 52, no 1, p. 65-78Article in journal (Refereed)
    Abstract [en]

    Global gene expression studies using microarray technology are widely employed to identify biological processes which are influenced by a treatment e.g. a specific diet. Affected processes are characterized by a significant enrichment of differentially expressed genes (functional annotation analysis). However, different choices of statistical thresholds to select candidates for differential expression will alter the resulting candidates list. This study was conducted to investigate the effect of applying a False Discovery Rate (FDR) correction and different fold change thresholds in statistical analysis of microarray data on diet-affected biological processes based on a significantly increased proportion of differentially expressed genes. In a model feeding experiment with rats fed genetically modified food additives, animals received a supplement of either lyophilized inactivated recombinant VP60 baculovirus (rBV-VP60) or lyophilized inactivated wild type baculovirus (wtBV). Comparative expression profiling was done in spleen, liver and small intestine mucosa. We demonstrated the extent to which threshold choice can affect the biological processes identified as significantly regulated and thus the conclusion drawn from the microarray data. In our study, the combined application of a moderate fold change threshold (FC≥1.5) and a stringent FDR threshold (q≤0.05) exhibited high reliability of biological processes identified as differentially regulated. The application of a stringent FDR threshold of q≤0.05 seems to be an essential prerequisite to reduce considerably the number of false positives. Microarray results of selected differentially expressed molecules were validated successfully by using real-time RT-PCR.

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  • 42.
    Hoefig, Kai P
    et al.
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Thorns, Christoph
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Roehle, Anja
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Kaehler, Christian
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Wesche, Kai O
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Repsilber, Dirk
    Biomathematics / Bioinformatics Group, Research Institute for the Biology of Farm Animals FBN, Dummerstorf, Germany.
    Branke, Biggi
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Thiere, Marlen
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Feller, Alfred C
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Merz, Hartmut
    Institute for Pathology, UKSH Campus Luebeck, Luebeck.
    Unlocking pathology archives for microRNA-profiling2008In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, no 1A, p. 119-123Article in journal (Refereed)
    Abstract [en]

    Background: MicroRNAs (miRNAs) are approximately 22 nucleotide long, non-coding RNAs that regulate gene expression by binding to the 3'-untranslated region of target mRNAs and also a variety of cellular processes. It has recently been established that dysregulation of miRNA expression can be detected in the majority of human cancers. A variety of high-throughput screening methods has been developed to identify dysregulated miRNA species in tumours. For retrospective clinical studies formalin-fixed, paraffin-embedded (FFPE) tissue is the most widely used material.

    Materials and methods: The miRNA expression profiles of freshly frozen (CRYO) and FFPE tissues of seven tonsil and four liver samples were compared, using a qPCR-based assay, profiling 157 miRNA species.

    Results: The significance of miRNA-profiles was barely influenced by FFPE treatment in both tissues and the variance induced by FFPE treatment was much smaller than the variance caused by biologically based differential expression.

    Conclusion: FFPE material is well suited for miRNA profiling.

  • 43.
    Hofner, Benjamin
    et al.
    Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
    Vaas, Lea
    Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Braunschweig, Germany.
    Lawo, John-Philip
    Global Drug Discovery Statistics, Bayer Pharma AG, Berlin, Germany.
    Müller, Tina
    Biostatistics / CRD Global Clinical Services, CSL Behring, Marburg, Germany.
    Sikorski, Johannes
    Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Braunschweig, Germany.
    Repsilber, Dirk
    Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
    Biologists meet Statisticians: A Workshop for young scientists to foster interdisciplinary team work2012Report (Other academic)
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    fulltext
  • 44.
    Holster, S.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Geng, D.
    Faculty of Business, Science and Engineering, School of Science and Technology, Örebro University, Örebro, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Salonen, A.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Rajan, Sukithar K
    Örebro University, School of Medical Sciences.
    De Vos, W. M.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, The Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndromeManuscript (preprint) (Other academic)
  • 45.
    Holster, S.
    et al.
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Geng, D.
    Faculty of Business, Science and Engineering, School of Science and Technology, Örebro University, Örebro, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Salonen, A.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Rajan, Sukithar K
    Örebro University, School of Medical Sciences.
    de Vos, W. M.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, the Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome2021In: Beneficial Microbes, ISSN 1876-2883, E-ISSN 1876-2891, Vol. 12, no 1, p. 17-30Article in journal (Refereed)
    Abstract [en]

    Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.

  • 46.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Fecal Microbiota Transplantation in Irritable Bowel Syndrome and a Randomized Placebo-Controlled Trial2017In: 2017 DDW Abstracts, Saunders Elsevier, 2017, Vol. 152, no 5, p. S101-S102Conference paper (Other academic)
  • 47.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Hooiveld, Guido J.
    Nutrition, Metabolism and Genomics group, Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    de Vos, Willem
    Laboratory of Microbiology, Wageningen University and Research Centre and Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome2019In: Biomolecules, E-ISSN 2218-273X, Vol. 9, no 10, article id 586Article in journal (Refereed)
    Abstract [en]

    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe–host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.

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    Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
  • 48.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Salonen, Anne
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    de Vos, Willem
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, the Netherlands.
    König, Julia
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study2019In: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 10, no 4, article id e00034Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.

    METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.

    RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P 5 0.02), which was not the case in the autologous group (P50.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor’s fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.

    CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.

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    The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study
  • 49.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in irritable bowel syndrome: clinical outcomes of a randomised placebo-controlled trial2017In: UEG Week 2017 Oral Presentations, Sage Publications, 2017, Vol. 5, p. A155-A156Conference paper (Refereed)
  • 50.
    Holster, Savanne
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Geng, Dawei
    Science and Engineering, School of Science and Technology, Örebro University, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    de Vos, W.
    Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Laboratory of Microbiology, Wageningen University and Research Centre, Wageningen, The Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    König, Julia
    Örebro University, School of Medical Sciences.
    Faecal microbiota transfer in irritable bowel syndrome results inaltered correlations between the gut microbiota and its metabolitesManuscript (preprint) (Other academic)
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