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  • 1.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Persson, B.
    cDepartment of Radiology, Karolinska Hospital, Stockholm, Sweden.
    Bindslev, L.
    Department of Anesthesiology and Intensive Care, Karolinska Hospital, Department of Anesthesiology and Intensive Care, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Intestinal amino acid content in critically ill patients1995In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 19, no 4, p. 272-278Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of the study was to determine the concentrations of free amino acids and the total protein content of the human intestinal mucosa during critical illness. Methods: The free amino acid and protein concentrations in endoscopically obtained biopsy specimens from the duodenum and the distal colonic segments were determined on 19 critically ill patients. The free amino acids were separated by ion exchange chromatography and detected by fluorescence, and the protein content was quantified by the method of Lowry. Results: In general, the typical amino acid pattern of the intestinal mucosa was seen, with very high levels of taurine, aspartate and glutamic acid. The main difference, as compared to a reference series of healthy subjects, was the elevated glutamine concentration of the duodenal mucosa. This amino acid was unaltered in the descending colon and depressed in the rectum. At the same time, the glutamatic acid concentrations were unaltered, suggesting that the degradation of glutamine was not increased in the septic state of the majority of the patients studied. Phenylalanine and the two branched-chain amino acids, valine and leucine, were elevated in the duodenal mucosa, and in the colonic mucosa, methionine and phenylalanine were elevated; otherwise, all the other individual amino acids were unaltered or depressed. Conclusions: The alterations seen in mucosal free amino acid and protein concentrations in connection with critical illness are different in many respects and contrast with the findings seen after starvation or moderate surgical trauma.

  • 2.
    Aura, Anna-Marja
    et al.
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Mattila, Ismo
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland.
    Gopalacharyulu, Peddinti
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Bounsaythip, Catherine
    University of Helsinki, Helsinki, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Oksman-Caldentey, Kirsi-Marja
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Drug metabolome of the simvastatin formed by human intestinal microbiota in vitro2011In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 7, no 2, p. 437-446Article in journal (Refereed)
    Abstract [en]

    The human colon contains a diverse microbial population which contributes to degradation and metabolism of food components. Drug metabolism in the colon is generally poorly understood. Metabolomics techniques and in vitro colon models are now available which afford detailed characterization of drug metabolites in the context of colon metabolism. The aim of this work was to identify novel drug metabolites of Simvastatin (SV) by using an anaerobic human in vitro colon model at body temperature coupled with systems biology platform, excluding the metabolism of the host liver and intestinal epithelia. Comprehensive two-dimensional gas chromatography with a time-of-flight mass spectrometry (GC×GC-TOFMS) was used for the metabolomic analysis. Metabolites showing the most significant differences in the active faecal suspension were elucidated in reference with SV fragmentation and compared with controls: inactive suspension or buffer with SV, or with active suspension alone. Finally, time courses of selected metabolites were investigated. Our data suggest that SV is degraded by hydrolytic cleavage of methylbutanoic acid from the SV backbone. Metabolism involves demethylation of dimethylbutanoic acid, hydroxylation/dehydroxylation and β-oxidation resulting in the production of 2-hydroxyisovaleric acid (3-methyl-2-hydroxybutanoic acid), 3-hydroxybutanoic acid and lactic acid (2-hydroxypropanoic acid), and finally re-cyclisation of heptanoic acid (possibly de-esterified and cleaved methylpyranyl arm) to produce cyclohexanecarboxylic acid. Our study elucidates a pathway of colonic microbial metabolism of SV as well as demonstrates the applicability of the in vitro colon model and metabolomics to the discovery of novel drug metabolites from drug response profiles.

  • 3. Björkblom, Carina
    et al.
    Olsson, Per-Erik
    Örebro University, Department of Natural Sciences.
    Katsiadaki, I
    Wiklund, T
    Estrogen- and androgen-sensitive bioassays based on primary cell and tissue slice cultures from three-spined stickleback (Gasterosteus aculeatus)2007In: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, ISSN 1532-0456, Vol. 146, no 3, p. 431-442Article in journal (Refereed)
    Abstract [en]

    Endocrine disrupting compounds are chemicals that may interfere with the endocrine system causing severe effects in organisms. The three-spined stickleback (Gasterosteus aculeatus L.) offers a potential for the assessment of endocrine disruption caused by a) estrogenic xenobiotics through the estrogen-dependent protein vitellogenin and b) androgenic xenobiotics through the androgen-dependent protein spiggin. The stickleback is presently the only known fish species with a quantifiable androgen and anti-androgen biomarker endpoint. In the current study, hepatocyte and kidney primary cell cultures and liver and kidney tissue slice cultures were prepared and used for detecting estrogenic or androgenic activity in vitro through the action of hormones or municipal sewage water. The results indicate that stickleback male hepatocyte cultures are suitable in detecting estrogenic activity and stickleback female kidney tissue slice cultures in detecting androgenic activity. The tested sewage water showed high estrogenic activity but no significant androgenic activity. Primary cell and tissue slice cultures isolated from the three-spined stickleback will allow simultaneously screening in vitro for potential estrogenic and androgenic activity of complex samples.

  • 4.
    Björnberg, Anna
    et al.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Inhibition of the growth of grain-storage molds in vitro by the yeast Pichia anomala (Hansen) Kurtzman1993In: Canadian journal of microbiology (Print), ISSN 0008-4166, E-ISSN 1480-3275, Vol. 39, no 6, p. 623-628Article in journal (Refereed)
    Abstract [en]

    The potential Use Of yeasts to control grain-storage molds was evaluated by coculturing the yeast Pichia anomala with Penicillium roqueforti and Aspergillus candidus on agar plates, using different temperatures, water activities (a(w)), and nutrient concentrations. Addition of 10 ppm cycloheximide to malt-extract agar inhibited Pichia anomala completely without affecting mold growth, making it possible to quantify the inhibition as a reduction in colony-forming units (cfu). For A. candidus, numbers of cfu and hyphal lengths were reduced at an initial yeast concentration of 10(4) cells/plate and reduced below detection limit at 10(8) cells/plate. A clear reduction in growth of Penicillium roqueforti was only observed at 10(8) yeast cells/plate. The antagonistic effect was generally more pronounced at low (6, 15-degrees-C) and high (30, 37-degrees-C) temperatures than at ambient ones. Pichia anomala inhibited growth of both molds more strongly in a substrate-rich medium than in a medium with a low substrate content. In water agar (low substrate concentration) the degree of inhibition of Penicillium roqueforti was larger at 0.96 a(w) than at 0.98 a(w).

  • 5.
    Blanc, Mélanie
    et al.
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Kukučka, Petr
    Örebro University, School of Science and Technology.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Keiter, Steffen
    Örebro University, School of Science and Technology.
    Mixture-specific gene expression in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonic acid (PFOS), perfluorohexanoic acid (PFHxA) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126)2017In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 590-591, p. 249-257Article in journal (Refereed)
    Abstract [en]

    Perfluorooctane sulfonic acid (PFOS) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways. For this purpose, zebrafish embryos were exposed in semi-static conditions to 7.5 μg/L of PCB126 alone, in the presence of 25 mg/L of PFOS, 15.7 mg/L of PFHxA or in the presence of both PFOS and PFHxA. Quantitative PCR was performed on embryos aged from 24 h post fertilization (hpf) to 96 hpf to investigate expression changes of genes involved in metabolism of xenobiotics (ahr2, cyp1a), oxidative stress (gpx1a, tp53), lipids metabolism (acaa2, osbpl1a), and epigenetic mechanisms (dnmt1, dnmt3ba). Cyp1a and ahr2 expression were significantly induced by the presence of PCB126. However, after 72 and 78 h of exposure, induction of cyp1a expression was significantly lower when embryos were co-exposed to PCB126 + PFOS + PFHxA when compared to PCB126-exposed embryos. Significant upregulation of gpx1a occurred after exposure to PCB126 + PFHxA and to PCB126 + PFOS + PFHxA at 30 and 48 hpf. Besides, embryos appeared more sensitive to PCB126 + PFOS + PFHxA at 78 hpf: acaa2 and osbpl1a were significantly downregulated; dnmt1 was significantly upregulated. While presented as environmentally safe, PFHxA demonstrated that it could affect gene expression patterns in zebrafish embryos when combined to PFOS and PCB126, suggesting that such mixture may increase PCB126 toxicity. This is of particular relevance since PFHxA is persistent and still being ejected into the environment. Moreover, it provides additional information as to the importance to integrate mixture effects of chemicals in risk assessment and biomonitoring frameworks.

  • 6. Brosché, Mikael
    et al.
    Gittins, John R.
    Sävenstrand, Helena
    Örebro University, Department of Natural Sciences.
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Gene expression under environmental stresses: molecular marker analysis2002In: Molecular techniques in crop improvement / [ed] S. Mohan Jain, D.S. Brar, B.S. Ahloowalia, Boston: Kluwer Academic Publishers, 2002, p. 371-408Chapter in book (Other academic)
  • 7. Brosché, Mikael
    et al.
    Schuler, Mary A.
    Kalbina, Irina
    Örebro University, Department of Natural Sciences.
    Connor, Lynn
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Gene regulation by low level UV-B radiation: identification by DNA array analysis2002In: Photochemical and Photobiological Sciences, ISSN 1474-905X, E-ISSN 1474-9092, Vol. 1, no 9, p. 656-664Article in journal (Refereed)
    Abstract [en]

    UV-B radiation alters transcript levels of various defence genes and photosynthetic genes in plants. Utilising a DNA array with 5000 ESTs and cDNAs from Arabidopsis thaliana, 70 genes were found to show a greater than two-fold induction or repression of transcript levels. Six genes (MEB5.2, PyroA, Ubq3, Lhcb6, F5D21.10 and the gene for an RNA polymerase II subunit) were tested for stress specific gene regulation on northern blots with RNA from plants exposed to low dose UV-B radiation, ozone or wounding. Transcript levels for PyroA, Uhq3 and the gene for a RNA polymerase II subunit were all specifically increased by UV-B. MEB5.2 mRNA levels also rose, whereas Lhcb6 and FSD21.10 transcript levels decreased under all stresses. The PyroA gene product in fungi is needed for biosynthesis of pyridoxine, and might have a role in protection against singlet oxygen. The Ubq3 gene encodes the ubiquitin protein that is attached to proteins destined for degradation. MEB5.2 and F5D21.10 represent novel gene products whose function have not yet been identified. Pairwise comparisons between the UV-B inducible promoters have identified a series of elements present in the MEB5.2 and PyroA promoters, absent from promoters of genes for early phenylpropanoid metabolism and that may be responsible for modulating their UV-B responses.

  • 8.
    Chaillou, Thomas
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lanner, Johanna T.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity2016In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 12, p. 3929-3941Article, review/survey (Refereed)
    Abstract [en]

    Reduced oxygen (O2) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O2 level could affect their activity during muscle regeneration. In this review, we present the idea that O2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O2 levels to promote muscle regeneration. Severe hypoxia (≤1% O2) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.

  • 9. Cheng, J
    et al.
    Johansson, Magnus
    Nordlund, S
    Expression of P(II) and glutamine synthetase is regulated by P(II), the ntrBC products, and processing of the glnBA mRNA in Rhodospirillum rubrum1999In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 181, no 20, p. 6530-6534Article in journal (Refereed)
    Abstract [en]

    We have studied the transcription of the glnB and glnA genes in Rhodospirillum rubrum with firefly luciferase as a reporter enzyme. Under NH(4)(+) and N(2) conditions, glnBA was cotranscribed from a weak and a strong promoter. In nitrogen-fixing cultures, activity of the latter was highly enhanced by NtrC, but transcription from both promoters occurred under both conditions. There is no promoter controlling transcription of glnA alone, supporting our proposal that the glnA mRNA is produced by processing.

  • 10.
    Chondrogianni, Niki
    et al.
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Sakellari, Marianthi
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Lefaki, Maria
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Papaevgeniou, Nikoletta
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Gonos, Efstathios S.
    Inst Biol Med Chem & Biotechnol, Natl Hellen Res Fdn, Athens, Greece.
    Proteasome activation delays aging in vitro and in vivo2014In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 71, p. 303-320Article, review/survey (Refereed)
    Abstract [en]

    Aging is a natural biological process that is characterized by a progressive accumulation of macromolecular damage. In the proteome, aging is accompanied by decreased protein homeostasis and function of the major cellular proteolytic systems, leading to the accumulation of unfolded, misfolded, or aggregated proteins. In particular, the proteasome is responsible for the removal of normal as well as damaged or misfolded proteins. Extensive work during the past several years has clearly demonstrated that proteasome activation by either genetic means or use of compounds significantly retards aging. Importantly, this represents a common feature across evolution, thereby suggesting proteasome activation to be an evolutionarily conserved mechanism of aging and longevity regulation. This review article reports on the means of function of these proteasome activators and how they regulate aging in various species. (C) 2014 Elsevier Inc. All rights reserved.

  • 11.
    Czégény, Gyula
    et al.
    Institute of Biology, University of Pécs, Pécs, Hungary; Institute of Plant Biology, Biological Research Centre, Szeged, Hungary.
    Wu, Min
    Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
    Dér, András
    Institute of Biophysics, Biological Research Centre, Szeged, Hungary.
    Eriksson, Leif A
    Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Hideg, Éva
    Institute of Biology, University of Pécs, Pécs, Hungary.
    Hydrogen peroxide contributes to the ultraviolet-B (280-315 nm) induced oxidative stress of plant leaves through multiple pathways2014In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 588, no 14, p. 2255-2261Article in journal (Refereed)
    Abstract [en]

    Solar UV-B (280-315 nm) radiation is a developmental signal in plants but may also cause oxidative stress when combined with other environmental factors. Using computer modelling and in solution experiments we show that UV-B is capable of photosensitizing hydroxyl radical production from hydrogen peroxide. We present evidence that the oxidative effect of UV-B in leaves is at least two-fold: (i) it increases cellular hydrogen peroxide concentrations, to a larger extent in pyridoxine antioxidant mutant pdx1.3-1 Arabidopsis and (ii) is capable of a partial photo-conversion of both ‘natural’ and ‘extra’ hydrogen peroxide to hydroxyl radicals. As stress conditions other than UV can increase cellular hydrogen peroxide levels, synergistic deleterious effects of various stresses may be expected already under ambient solar UV-B.

  • 12.
    Dinoto, Achmad
    et al.
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido .
    Marques, Tatiana M.
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido.
    Sakamoto, Kanta
    Creative Research Initiative Sousei (CRIS), Hokkaido University, Sapporo, Japan.
    Fukiya, Satoru
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido.
    Watanabe, Jun
    Creative Research Initiative Sousei (CRIS), Hokkaido University, Sapporo, Japan.
    Ito, Susumu
    Creative Research Initiative Sousei (CRIS), Hokkaido University, Sapporo, Japan.
    Yokota, Atsushi
    Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Sapporo, Hokkaido.
    Population dynamics of Bifidobacterium species in human feces during raffinose administration monitored by fluorescence in situ hybridization-flow cytometry2006In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 72, no 12, p. 7739-47Article in journal (Refereed)
    Abstract [en]

    The population dynamics of bifidobacteria in human feces during raffinose administration were investigated at the species level by using fluorescence in situ hybridization (FISH) coupled with flow cytometry (FCM) analysis. Although double-staining FISH-FCM using both fluorescein isothiocyanate (FITC) and indodicarbocyanine (Cy5) as labeling dyes for fecal samples has been reported, the analysis was interfered with by strong autofluorescence at the FITC fluorescence region because of the presence of autofluorescence particles/debris in the fecal samples. We circumvented this problem by using only Cy5 fluorescent dye in the FISH-FCM analysis. Thirteen subjects received 2 g of raffinose twice a day for 4 weeks. Fecal samples were collected, and the bifidobacterial populations were monitored using the established FISH-FCM method. The results showed an increase in bifidobacteria from about 12.5% of total bacteria in the prefeeding period to about 28.7 and 37.2% after the 2-week and 4-week feeding periods, respectively. Bifidobacterium adolescentis, the Bifidobacterium catenulatum group, and Bifidobacterium longum were the major species, in that order, at the prefeeding period, and these bacteria were found to increase nearly in parallel during the raffinose administration. During the feeding periods, indigenous bifidobacterial populations became more diverse, such that minor species in human adults, such as Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium dentium, and Bifidobacterium angulatum, proliferated. Four weeks after raffinose administration was stopped, the proportion of each major bifidobacterial species, as well as that of total bifidobacteria, returned to approximately the original values for the prefeeding period, whereas that of each minor species appeared to differ considerably from its original value. To the best of our knowledge, these results provide the first clear demonstration of the population dynamics of indigenous bifidobacteria at the species level in response to raffinose administration.

  • 13.
    Duszka, Kalina
    et al.
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Center for Integrative Genomics, University of Lausanne, Génopode, Lausanne, Switzerland; Department of Nutritional Sciences, University of Vienna, Vienna, Austria.
    Oresic, Matej
    Turku Centre for Biotechnology, University of Turku and Åbo Akademi University,Turku, Finland.
    Le May, Cedric
    Institut du Thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
    König, Jürgen
    Department of Nutritional Sciences, University of Vienna, Vienna, Austria; Vienna Metabolomics Center (VIME), University of Vienna, Vienna, Austria.
    Wahli, Walter
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Center for Integrative Genomics, University of Lausanne Génopode, Lausanne, Switzerland; ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), Toulouse, France.
    PPARγ Modulates Long Chain Fatty Acid Processing in the Intestinal Epithelium2017In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 18, no 12, article id E2559Article in journal (Refereed)
    Abstract [en]

    Nuclear receptor PPARγ affects lipid metabolism in several tissues, but its role in intestinal lipid metabolism has not been explored. As alterations have been observed in the plasma lipid profile of ad libitum fed intestinal epithelium-specific PPARγ knockout mice (iePPARγKO), we submitted these mice to lipid gavage challenges. Within hours after gavage with long chain unsaturated fatty acid (FA)-rich canola oil, the iePPARγKO mice had higher plasma free FA levels and lower gastric inhibitory polypeptide levels than their wild-type (WT) littermates, and altered expression of incretin genes and lipid metabolism-associated genes in the intestinal epithelium. Gavage with the medium chain saturated FA-rich coconut oil did not result in differences between the two genotypes. Furthermore, the iePPARγKO mice did not exhibit defective lipid uptake and stomach emptying; however, their intestinal transit was more rapid than in WT mice. When fed a canola oil-rich diet for 4.5 months, iePPARγKO mice had higher body lean mass than the WT mice. We conclude that intestinal epithelium PPARγ is activated preferentially by long chain unsaturated FAs compared to medium chain saturated FAs. Furthermore, we hypothesize that the iePPARγKO phenotype originates from altered lipid metabolism and release in epithelial cells, as well as changes in intestinal motility.

  • 14.
    Dzialanski, Zbigniew
    et al.
    University Health Care Research Center, Region Örebro County, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Barany, Michael
    Department of Clinical Physiology, Örebro University Hospital, Örebro, Sweden; School of Health and Medicine Sciences, Örebro University, Örebro, Sweden.
    Engfeldt, Peter
    Örebro University, School of Medical Sciences. University Health Care Research Center, Region Örebro County, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    School of Health and Medicine Sciences, Örebro University, Örebro, Sweden.
    Olsson, Lovisa A.
    Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Faculty of Medicine and Health, Umeå University, Umeå, Sweden.
    Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?2016In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 49, no 3, p. 248-252Article in journal (Refereed)
    Abstract [en]

    Background: According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist.

    Aim: To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test.

    Methods: A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274).

    Results: Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups.

    Conclusions: Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.

  • 15.
    Díaz-Ramos, L. Aranzazú
    et al.
    Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Bower Building, University of Glasgow, Glasgow, UK.
    O'Hara, Andrew
    Örebro University, School of Science and Technology. Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Bower Building, University of Glasgow, Glasgow, UK.
    Kanagarajan, Selvaraju
    Department of Plant Breeding, Swedish University of Agricultural Sciences, Alnarp, Sweden; School of Science & Technology, Örebro Life Science Center, Örebro University, Örebro, Sweden.
    Farkas, Daniel
    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Jenkins, Gareth I
    Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Bower Building, University of Glasgow, Glasgow, UK.
    Difference in the action spectra for UVR8 monomerisation and HY5 transcript accumulation in Arabidopsis2018In: Photochemical and Photobiological Sciences, ISSN 1474-905X, E-ISSN 1474-9092, Vol. 17, no 8, p. 1108-1117Article in journal (Refereed)
    Abstract [en]

    The photoreceptor UV RESISTANCE LOCUS 8 (UVR8) activates photomorphogenic responses when plants are exposed to ultraviolet-B (UVB) light. However, whereas the absorption spectrum of UVR8 peaks at 280 nm, action spectra for several photomorphogenic UV-B responses show maximal photon effectiveness at 290-300 nm. To investigate this apparent discrepancy we measured the effectiveness of UV wavelengths in initiating two responses in Arabidopsis: photoconversion of homodimeric UVR8 into the monomeric form, which is active in signaling, and accumulation of transcripts of the ELONGATED HYPOCOTYL 5 (HY5) transcription factor, which has a key role in UVR8-mediated responses. When purified UVR8 or Arabidopsis leaf extracts were exposed to UV light monomerisation was maximal at approximately 280 nm, which correlates with the UVR8 absorption spectrum. When intact plants were exposed to UV, monomerisation was most strongly initiated at approximately 290 nm, and this shift in maximal effectiveness could be explained by strong absorption or reflectance at 280 nm by leaf tissue. Notably, the action spectrum for accumulation of HY5 transcripts in the same leaf tissue samples used to assay UVR8 dimer/monomer status peaked at approximately 300 nm. Possible reasons for the difference in maximal photon effectiveness of UVR8 monomerisation and HY5 transcript accumulation in leaf tissue are discussed.

  • 16.
    Fang, Xin
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Liang, Chun
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Li, Mei
    Department of Cardiology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Fall, Katja
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Aaseth, Jan
    Faculty of Public Health, Hedmark University College, Elverum, Norway; Kongsvinger Hospital Division, Innlandet Hospital Trust, Kongsvinger, Norway.
    Cao, Yang
    Örebro University, School of Medical Sciences. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies2016In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 38, p. 64-73Article in journal (Refereed)
    Abstract [en]

    Background: Although epidemiology studies have reported the relationship, including a dose-response relationship, between dietary magnesium intake and risk of cardiovascular disease (CVD), the risk for CVD mortality is inconclusive and the evidence for a dose-response relationship has not been summarized.

    Objective: We conducted a systematic review and meta-analysis of prospective studies to summarize the evidence regarding the association of dietary magnesium intake with risk of CVD mortality and describe their dose-response relationship.

    Design: We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to August 2015, and reviewed references lists of retrieved articles. We included population-based studies that reported mortality risks, i.e. relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs) of CVD mortality or cause-specific CVD death. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines.

    Results: Out of 3002 articles, 9 articles from 8 independent studies met the eligibility criteria. These studies comprised 449,748 individuals and 10,313 CVD deaths. Compared with the lowest dietary magnesium consumption group in the population, the risk of CVD mortality was reduced by 16% in women and 8% in men. No significant linear dose-response relationship was found between increment in dietary magnesium intake and CVD mortality across all the studies. After adjusting for age and BMI, the risk of CVD mortality was reduced by 24-25% per 100 mg/d increment in dietary magnesium intake in women of all the participants and in all the US participants.

    Conclusion: Although the combined data confirm the role of dietary magnesium intake in reducing CVD mortality, the dose-response relationship was only found among women and in US population.

  • 17.
    Farkas, Sanja
    Örebro University, School of Science and Technology. Örebro University.
    Development of a UV-B marker in plants2009Licentiate thesis, monograph (Other academic)
  • 18.
    Filonova, Lada
    et al.
    WURC, Department of Wood Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Gunnarsson, Lavinia Cicortas
    Örebro University. Department of Immunotechnology, Lund University, Lund, Sweden; Affitech AS, Oslo, Norway.
    Daniel, Geoffrey
    WURC, Department of Wood Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Synthetic xylan-binding modules for mapping of pulp fibres and wood sections2007In: BMC Plant Biology, ISSN 1471-2229, E-ISSN 1471-2229, Vol. 7, article id 54Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The complex carbohydrate composition of natural and refined plant material is not known in detail but a matter that is of both basic and applied importance. Qualitative assessment of complex samples like plant and wood tissues requires the availability of a range of specific probes. Monoclonal antibodies and naturally existing carbohydrate binding modules (CBMs) have been used in the past to assess the presence of certain carbohydrates in plant tissues. However, the number of natural CBMs is limited and development of carbohydrate-specific antibodies is not always straightforward. We envisage the use of sets of very similar proteins specific for defined targets, like those developed by molecular evolution of a single CBM scaffold, as a suitable strategy to assess carbohydrate composition. An advantage of using synthetic CBMs lies in the possibility to study fine details of carbohydrate composition within non-uniform substrates like plant cell walls as made possible through minor differences in CBM specificity of the variety of binders that can be developed by genetic engineering.

    RESULTS: A panel of synthetic xylan-binding CBMs, previously selected from a molecular library based on the scaffold of CBM4-2 from xylanase Xyn10A of Rhodothermus marinus, was used in this study. The wild type CBM4-2 and evolved modules both showed binding to wood sections. However, differences were observed in the staining patterns suggesting that these modules have different xylan-binding properties. Also the staining stability varied between the CBMs, the most stable staining being obtained with one (X-2) of the synthetic modules. Treatment of wood materials resulted in altered signal intensities, thereby also demonstrating the potential application of engineered CBMs as analytical tools for quality assessment of diverse plant material processes.

    CONCLUSION: In this study we have demonstrated the usefulness of synthetic xylan-binding modules as specific probes in analysis of hemicelluloses (xylan) in wood and fibre materials.

  • 19.
    Finckenberg, Piet
    et al.
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Eriksson, Ove
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Baumann, Marc
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Merasto, Saara
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Lalowski, Maciej M.
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Levijoki, Jouko
    Orion Pharma Ltd, Espoo, Finland.
    Haasio, Kristiina
    Orion Pharma Ltd, Espoo, Finland.
    Kytö, Ville
    Department of Medicine, Turku University Hospital, Turku, Finland.
    Muller, Dominik N.
    Experimental and Clinical Research Center, Max Delbrück Center, Berlin, Germany.
    Luft, Friedrich C.
    Experimental and Clinical Research Center, Max Delbrück Center, Berlin, Germany.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Mervaala, Eero
    Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
    Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy2012In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 59, no 1, p. 76-84Article in journal (Refereed)
    Abstract [en]

    Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications.

  • 20.
    Fornander, Louise
    Institutionen för klinisk och experimentell medicin, Linköpings universitet, Linköping, Sweden.
    Upper Airway Mucosal Inflammation: Proteomic Studies after Exposure to Irritants and Microbial Agents2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    People are, in their daily lives, exposed to a number of airborne foreign compounds that do not normally affect the body. However, depending on the nature of these compounds, dose and duration of exposure, various airway symptoms may arise. Early symptoms are often manifested as upper airway mucosal inflammation which generates changes in protein composition in the airway lining fluid.

    This thesis aims at identifying, understanding mechanisms and characterizing protein alterations in the upper airway mucosa that can be used as potential new biomarkers for inflammation in the mucosa. The protein composition in the mucosa was studied by sampling of nasal lavage fluid that was further analyzed with a proteomic approach using twodimensional gel electrophoresis and mass spectrometry. Additionally, by studying factors on site through environmental examination, health questionnaires and biological analyses, we have tried to understand the background to these protein alterations and their impact on health.

    Respiratory symptoms from the upper airways are common among people who are exposed to irritative and microbial agents. This thesis have focused on personnel in swimming pool facilities exposed to trichloramine, metal industry workers exposed to metalworking fluids, employees working in damp and moldy buildings and infants diagnosed with respiratory syncytial virus infection. The common denominator in these four studies is that the subjects experience upper airway mucosal inflammation, which is manifested as cough, rhinitis, phlegm etc. In the three occupational studies, the symptoms were work related. Notably, a high prevalence of perceived mucosal symptoms was shown despite the relatively low levels of airborne irritants revealed by the environmental examination. Protein profiling verified an ongoing inflammatory response by identification of several proteins that displayed altered levels. Interestingly, innate immune proteins dominated and four protein alterations occurred in most of the studies; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin. Similarly, these proteins were also found in nasal fluid from children with virus infection and in addition a truncated form of SPLUNC1 and two other S100 proteins (S100A7-like 2 and S100A16), not previously found in nasal secretion, were identified.

    Altogether, the results indicate the potential use of a proteomic approach for identifying new biomarkers for the upper respiratory tract at an early stage in the disease process after exposure to irritant and microbial agents. The results indicate an effect on the innate immunity system and the proteins; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin are especially promising new biomarkers. Moreover, further studies of these proteins may help us to understand the molecular mechanisms involved in irritant-induced airway inflammation.

  • 21.
    Fredlund, Elisabeth
    et al.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Boysen, Marianne
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Broberg, Anders
    Department of Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Exploring the mode of action of Pichia anomala - a postharvest biocontrol yeast2001In: Yeast, ISSN 0749-503X, E-ISSN 1097-0061, Vol. 18, p. S212-S212Article in journal (Other academic)
    Abstract [en]

    The ascomycetous yeast Pichia anomala J121, inhibits mould growth in malfunctioning airtight storage systems for moist animal feed grain. Extensive studies of P. anomala J121 have given detailed knowledge of growth physiology and limiting environmental factors, which is necessary to understand the inhibitory activity. Our main objective is to identify the mechanisms behind the inhibitory activity. We have two non-exclusive working hypothesis: I)P. anomala produces antifungal substances and II)P. anomala out-competes the mould for space, nutrients, and oxygen. We have found that volatile metabolites restrict radial growth and sporulation of moulds in mouth-to-mouth assays where agar plates are placed facing each other with the yeast inoculated on the upper plate and the mould on the lower. Previous studies of P. anomala have shown that it produces high quantities of ethyl acetate - a mould-inhibitory substance. We are working to identify homologous genes in P. anomala J121 to the acetyltransferase encoding genes ATF1 and ATF2 in Saccharomyces cerevisiae. Another approach has been to identify intra- and extracellular metabolites during aerobic and oxygen limited growth. Intracellular metabolites were identified by Magic Angle Spinning-High Resolution-Nuclear Magnetic Resonance (MAS-HR- NMR) that allows analysis of living cells. Extracellular metabolites were analysed with HPLC. Glycerol, well known for its role during osmotic stress, is accumulated in response to oxygen stress.

  • 22.
    Fredlund, Elisabeth
    et al.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Druvefors, Ulrika Ädel
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Passoth, Volkmar
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    The correlation of oxygen and sugar dependent regulation of glycolysis to the biocontrol activity of the yeast Pichia anomala2003In: Yeast, ISSN 0749-503X, E-ISSN 1097-0061, Vol. 20, p. S352-S352Article in journal (Other academic)
    Abstract [en]

    Pichia anomala inhibits growth of mould during airtight storage of moist cereal grain for animal feed. The cereal grain is stored in large airtight containers where the anaerobic environment prevents growth of mould. Air can leak into the system due to the removal of grain or technical difficulties in keeping completely anaerobic conditions. This subsequently enables growth of spoilage moulds. Addition of P. anomala cells inhibits the growth of mould making the system more robust [1]. We analysed the physiological basis of the biocontrol activity. P. anomala is a Crabtree negative yeast but in contrast to other Crabtree negative organisms it can grow under anaerobic conditions [2]. The ability to switch between respiratory and fermentative growth in response to O2-availability is essential for its survival in the airtight system and for its biocontrol activity. End products of the sugar metabolism had inhibitory effects on mould growth. Addition of glucose to a model biocontrol system enhanced biocontrol activity without increasing yeast biomass, suggesting the involvement of a product of glycolysis in biocontrol. Sugar consumption, production of ethanol and other metabolites and the activity of key enzymes were investigated in cells grown under defined conditions of oxygen and nutrient supply. The impact of the different parameters on biocontrol activity is discussed. [1] Druvefors et al. (2002) FEMS Yeast Res. 2: 389-394 [2] Fredlund et al. (2002) FEMS Yeast Res. 2: 395-402

  • 23.
    Frändberg, Emma
    et al.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Petersson, Carl
    Department of Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Lundgren, Lennart N.
    Department of Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Streptomyces halstedii K122 produces the antifungal compounds bafilomycin B1 and C12000In: Canadian journal of microbiology (Print), ISSN 0008-4166, E-ISSN 1480-3275, Vol. 46, no 8, p. 753-758Article in journal (Refereed)
    Abstract [en]

    Streptomyces halstedii K122 was previously found to produce antifungal compounds on solid substrates that inhibit radial growth of fungi among Ascomycetes, Basidiomycetes, Deuteromycetes, Oomycetes, and Zygomycetes, and strongly affected hyphal branching and morphology. During growth of S. halstedii K122 in submerged culture, no antifungal activity could be detected. However, cultivation of S. halstedii in thin (1 mm) liquid substrate layers in large surface-area tissue culture flasks caused intense growth and sporulation of S. halstedii K122, and the biologically active compounds could be extracted from the mycelium with methanol. Antifungal compounds were purified using C18 solid phase extraction and silica gel column chromatography, and identified as bafilomycins B1 and C1, using 2D NMR and FAB MS. Production of bafilomycins, which are specific inhibitors of vacuolar ATPases, has not been reported from S. halstedii previously. Minimum inhibitory concentrations (MIC) of bafilomycins BI and C1, amphotericin B, and nikkomycin Z were determined at pH 5.5 and 7.0 for the target fungi Aspergillus fumigatus, Mucor hiemalis, Penicillium roqueforti, and Paecilomyces variotii. Penicillium roqueforti was the most sensitive species to all the compounds investigated. The MIC values for amphotericin B were 0.5-4 mu g.mL(-1) for the fungi tested, and pH did not affect the toxicity. The MIC values for nikkomycin Z ranged from <0.5 mu g.mL(-1) for Mucor hiemalis to >500 mu g.mL(-1) for Aspergillus fumigatus, and pH had no influence on toxicity. Bafilomycins B1 and C1 were equally active against the fungal species tested, with MIC values in the range of <0.5-64 mu g.mL(-1). All fungi were more sensitive to both bafilomycin B1 and C1 at pH 7.0 than at pH 5.5.

  • 24.
    Frändberg, Emma
    et al.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Antifungal activity of chitinolytic bacteria isolated from airtight stored cereal grain1998In: Canadian journal of microbiology (Print), ISSN 0008-4166, E-ISSN 1480-3275, Vol. 44, no 2, p. 121-127Article in journal (Refereed)
    Abstract [en]

    Chitinolytic bacteria are used as biocontrol agents of plant pathogenic fungi. They might also potentially inhibit growth of molds, e.g., Aspergillus spp. and Penicillium spp., in stored plant material. We isolated chitinolytic bacteria from airtight stored cereal grain and evaluated their antifungal capacity. Between 0.01 and 0.5% of the total aerobic counts were chitinolytic bacteria. Gram-negative bacteria, mainly Pseudomonadaceae, constituted approximately 80% of the chitinolytic population. Gram-positive isolates belonged predominantly to the Corynebacterium-Arthrobacter group, Streptomyces, and Bacillus. Chitinolytic activity was evaluated using culture filtrates from chitin-grown isolates as the release of p-nitrophenol from p-nitrophenyl N,N'-diacetylchitobiose and as the formation of clearing zones on chitin agar. No correlation between chitinolytic activity and antifungal effects was found when challenging Penicillium roqueforti Dierckx with bacterial isolates on chitin agar in a dual culture bioassay. Fungal hyphae frequently grew seemingly unaffected through the bacterial colony of a high chitinase producer on colloidal chitin. Only 4% of the chitinolytic isolates had strong effects on fungal growth. Among these, Streptomyces halstedii (K122) and Streptomyces coelicolor (K139) inhibited growth of a broad range of fungi. Streptomyces halstedii affected hyphal morphology and decreased the radial growth rate of all fungi investigated. These effects were not caused by volatile metabolites, polyenes, or N-carbamoyl-D-glucosamine.

  • 25.
    Grahn, Elin M.
    et al.
    Örebro University, School of Science and Technology.
    Winter, Harry C.
    University of Michigan.
    Tateno, Hiroaki
    University of Michigan.
    Goldstein, Irwin J.
    University of Michigan.
    Krengel, Ute
    University of Olso.
    Structural Characterization of a Lectin from the  Mushroom Marasmius oreades in Complex with the  Blood Group B Trisaccharide and Calcium2009In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 390, no 3, p. 457-466Article in journal (Refereed)
    Abstract [en]

    MOA (Marasmius oreades agglutinin), a lectin isolated from fruiting bodies of the mushroom M. oreades, specifically binds nonreducing terminal Galα(1,3)Gal carbohydrates, such as that which occurs in the xenotransplantation epitope Galα(1,3)Galβ(1,4)GlcNAc and the branched blood group B determinant Galα(1,3)[Fucα(1,2)]Gal. Here, we present the crystal structure of MOA in complex with the blood group B trisaccharide solved at 1.8 Å resolution. To our knowledge, this is the first blood-group-B-specific structure reported in complex with a blood group B determinant. The carbohydrate ligand binds to all three binding sites of the N-terminal β-trefoil domain. Also, in this work, Ca2+ was included in the crystals, and binding of Ca2+ to the MOA homodimer altered the conformation of the C-terminal domain by opening up the cleft containing a putative catalytic site.

  • 26.
    Gunnarsson, Lavinia Cicortas
    et al.
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Dexlin, Linda
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Karlsson, Eva Nordberg
    Department of Biotechnology, Lund University, Lund, Sweden.
    Holst, Olle
    Department of Biotechnology, Lund University, Lund, Sweden.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Evolution of a carbohydrate binding module into a protein-specific binder2006In: Biomolecular Engineering, ISSN 1389-0344, E-ISSN 1878-559X, Vol. 23, no 2-3, p. 111-117Article in journal (Refereed)
    Abstract [en]

    A carbohydrate binding module, CBM4-2, derived from the xylanase (Xyn 10A) of Rhodothermus marinus has been used as a scaffold for molecular diversification. Its binding specificity has been evolved to recognise a quite different target, a human monoclonal IgG4. In order to understand the basis for this drastic change in specificity we have further investigated the target recognition of the IgG4-specific CBMs. Firstly, we defined that the structure target recognised by the selected CBM-variants was the protein and not the carbohydrates attached to the glycoprotein. We also identified key residues involved in the new specificity and/or responsible for the swap in specificity, from xylan to human IgG4. Specific changes present in all these CBMs included mutations not introduced in the design of the library from which the specific clones were selected. Reversion of such mutations led to a complete loss of binding to the target molecule, suggesting that they are critical for the recognition of human IgG4. Together with the mutations introduced at will, they had transformed the CBM scaffold into a protein binder. We have thus shown that the scaffold of CBM4-2 is able to harbour molecular recognition for either carbohydrate or protein structures.

  • 27.
    Gunnarsson, Lavinia Cicortas
    et al.
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Montanier, Cedric
    Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
    Tunnicliffe, Richard B
    Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.
    Williamson, Mike P
    Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.
    Gilbert, Harry J
    Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
    Nordberg Karlsson, Eva
    Department of Biotechnology, Lund University, Lund, Sweden.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Novel xylan-binding properties of an engineered family 4 carbohydrate-binding module2007In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 406, no 2, p. 209-214Article in journal (Refereed)
    Abstract [en]

    Molecular engineering of ligand-binding proteins is commonly used for identification of variants that display novel specificities. Using this approach to introduce novel specificities into CBMs (carbohydrate-binding modules) has not been extensively explored. Here, we report the engineering of a CBM, CBM4-2 from the Rhodothermus marinus xylanase Xyn10A, and the identification of the X-2 variant. As compared with the wild-type protein, this engineered module displays higher specificity for the polysaccharide xylan, and a lower preference for binding xylo-oligomers rather than binding the natural decorated polysaccharide. The mode of binding of X-2 differs from other xylan-specific CBMs in that it only has one aromatic residue in the binding site that can make hydrophobic interactions with the sugar rings of the ligand. The evolution of CBM4-2 has thus generated a xylan-binding module with different binding properties to those displayed by CBMs available in Nature.

  • 28.
    Gunnarsson, Lavinia Cicortas
    et al.
    Department of Immunotechnology, Lund University, Lund.
    Nordberg Karlsson, E
    Department of Biotechnology, Lund University, Lund.
    Albrekt, A-S
    Department of Immunotechnology, Lund University, Lund.
    Andersson, M
    Alligator Bioscience, Lund, Sweden.
    Holst, O
    Department of Biotechnology, Lund University, Lund.
    Ohlin, M
    Department of Immunotechnology, Lund University, Lund.
    A carbohydrate binding module as a diversity-carrying scaffold2004In: Protein Engineering Design & Selection, ISSN 1741-0126, E-ISSN 1741-0134, Vol. 17, no 3, p. 213-221Article in journal (Refereed)
    Abstract [en]

    The growing field of biotechnology is in constant need of binding proteins with novel properties. Not just binding specificities and affinities but also structural stability and productivity are important characteristics for the purpose of large-scale applications. In order to find such molecules, libraries are created by diversifying naturally occurring binding proteins, which in those cases serve as scaffolds. In this study, we investigated the use of a thermostable carbohydrate binding module, CBM4-2, from a xylanase found in Rhodothermus marinus, as a diversity-carrying scaffold. A combinatorial library was created by introducing restricted variation at 12 positions in the carbohydrate binding site of the CBM4-2. Despite the small size of the library (1.6 x 10(6) clones), variants specific towards different carbohydrate polymers (birchwood xylan, Avicel and ivory nut mannan) as well as a glycoprotein (human IgG4) were successfully selected for, using the phage display method. Investigated clones showed a high productivity (on average 69 mg of purified protein/l shake flask culture) when produced in Escherichia coli and they were all stable molecules displaying a high melting transition temperature (75.7 +/- 5.3 degrees C). All our results demonstrate that the CBM4-2 molecule is a suitable scaffold for creating variants useful in different biotechnological applications.

  • 29.
    Gunnarsson, Lavinia Cicortas
    et al.
    Department of Immunotechnology, Lund University, Lund.
    Nordberg Karlsson, Eva
    Department of Biotechnology, Lund University, Lund.
    Andersson, Mats
    Alligator Bioscience, Lund, Sweden.
    Holst, Olle
    Department of Biotechnology, Lund University, Lund.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund.
    Molecular engineering of a thermostable carbohydrate-binding module2006In: Biocatalysis and Biotransformation, ISSN 1024-2422, E-ISSN 1029-2446, Vol. 24, no 1-2, p. 31-37Article in journal (Refereed)
    Abstract [en]

    Structure-function studies are frequently practiced on the very diverse group of natural carbohydrate-binding modules in order to understand the target recognition of these proteins. We have taken a step further in the study of carbohydrate-binding modules and created variants with novel binding properties by molecular engineering of one such molecule of known 3D-structure. A combinatorial library was created from the sequence encoding a thermostable carbohydrate-binding module, CBM4-2 from a Rhodothermus marinus xylanase, and phage-display technology was successfully used for selection of variants with specificity towards different carbohydrate polymers (birchwood xylan, Avicel (TM), ivory nut mannan and recently also xyloglucan), as well as towards a glycoprotein (human IgG4). Our work not only generated a number of binders with properties that would suite a range of biotechnological applications, but analysis of selected binders also helped us to identify residues important for their specificities.

  • 30.
    Gunnarsson, Lavinia Cicortas
    et al.
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Zhou, Qi
    School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Center, Stockholm, Sweden.
    Montanier, Cedric
    Institute for Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
    Karlsson, Eva Nordberg
    Department of Biotechnology, Lund University, Lund, Sweden.
    Brumer, Harry
    School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Center, Stockholm, Sweden.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Engineered xyloglucan specificity in a carbohydrate-binding module2006In: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 16, no 12, p. 1171-1180Article in journal (Refereed)
    Abstract [en]

    The field of plant cell wall biology is constantly growing and consequently so is the need for more sensitive and specific probes for individual wall components. Xyloglucan is a key polysaccharide widely distributed in the plant kingdom in both structural and storage tissues that exist in both fucosylated and non-fucosylated variants. Presently, the only xyloglucan marker available is the monoclonal antibody CCRC-M1 that is specific to terminal alpha-1,2-linked fucosyl residues on xyloglucan oligo- and polysaccharides. As a viable alternative to searches for natural binding proteins or creation of new monoclonal antibodies, an approach to select xyloglucan-specific binding proteins from a combinatorial library of the carbohydrate-binding module, CBM4-2, from xylanase Xyn10A of Rhodothermus marinus is described. Using phage display technology in combination with a chemoenzymatic method to anchor xyloglucan to solid supports, the selection of xyloglucan-binding modules with no detectable residual wild-type xylan and beta-glucan-binding ability was achieved.

  • 31.
    Hadad, Ronza
    Örebro University, Department of Clinical Medicine.
    Neisseria gonorrhoeae populationen i Sverige under 2005 - serologiska och genetiska karaktäristika2006Student thesis
    Abstract [sv]

    Neisseria gonorrhoeae orsakar den sexuellt överförbara sjukdomen gonorré som fortfarande utgör ett stort folkhälsoproblem världen över. Karaktärisering av bakterien för epidemiologiska syften är mycket viktigt för att en begränsning av sjukdomen. Serologisk karaktärisering av yttermembranproteinet PorB indelar isolat i de serologiska grupperna PorB1a och PorB1b och ytterligare i serologiska varianter (serovarer). Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) innefattar sekvensering av porB genen samt genen för transferrinbindande protein subenhet B. Gensekvenserna kan med NG-MAST tilldelas specifika allelnummer via en internetbaserad databas och som tillsammans ger upphov till en sekvenstyp (ST). Syftet var att beskriva den cirkulerande populationen av N. gonorrhoeae isolat i Sverige under 2005 genom serologisk karaktärisering samt ett urval av isolaten med genetiska metoder och jämföra de två vanligaste systemen för serologisk karaktärisering, Pharmacia och Genetic systems. Det var en högst diversifierad N. gonorrhoeae population som cirkulerade i Sverige under 2005. Resultatet av serovarbestämningen visade på en relativt låg överensstämmelse mellan de olika systemen av monoklonala antikroppar och den genetiska karaktäriseringen visade på en ökad diskriminering och det identifierades relativt många nya ST. Det höga antalet av skilda serovarer och genetiska varianter kan spegla en hög import av stammar från andra länder, suboptimal diagnostik eller inkomplett partnerspårning. Många kluster av isolat med samma serovar och ST identifierades dock vilket kan reflektera att flera smittkedjor existerar. NG-MAST kan komplettera den serologiska karaktäriseringen eller på sikt ersätta den.

  • 32.
    Hadad, Ronza
    et al.
    Örebro University, School of Science and Technology.
    Schön, Karin
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Lycke, Nils
    University of Gothenburg, Gothenburg, Sweden.
    Optimization of infection in murine model with Chlamydia trachomatis for vaccine studies2013In: Chlamydia Basic Research Society: 2013 biannual meeting, 2013Conference paper (Refereed)
    Abstract [en]

    Background and Significance: Vaccine studies for Chlamydia trachomatis (Ct) have been hampered by the lack of an ideal murine model. Ct is not ideal for infection and subsequent pathology as it is a human pathogen and C. muridarum (Cm) may not be suitable due to vaccine specificity for Ct. There is currently no standardization of chlamydial infections in murine models concerning mouse strain, infecting agent and dose.

     

    Objectives: To investigate the Ct infection in mice, using different suppliers of mice, doses and the infective agents of Ct serovars D, E and Cm.

     

    Methods: C57BL/6 mice (Taconic; Harlan; in-house breeding mice) were inoculated intravaginally with 103-105 chlamydia  elementary bodies (EB). Vaginal samples were collected at 7-8 days intervals and analyzed using MicroTrak II Chlamydia EIA kit.

     

    Results: Taconic mice inoculated with Ct D with 105 EB showed the strongest infection with 30% of mice infected at day 21 (d21) as seen in figure 1. The number of infected mice and detected antigen (not shown) decreased rapidly after the first time-point (d8). In figure 2 infective agents were analyzed. Ct E did not infect any mice despite using a tenfold increased dose. Cm infection was detectable in 80% of the mice for up to d21.

     

    Conclusions: Ct D infected the mice for a period of 2-3 weeks. There was only a small difference between the suppliers in favor for Harlan mice. Ct D 105 EB was the infectious dose with the highest number of infected mice over time, however the appropriateness of that high bacterial load must be considered. Ct E did not infect these mice and Cm, a mouse pneumonitis strain, infected all mice and had the longest duration of infection. However, for vaccine studies, Cm may not be suitable due to lack of cross reactivity and Ct may still be used however vaginal sampling must be more frequent early on to show significant differences in bacterial shedding between immunized and non-immunized mice. 

  • 33.
    Hansson, Charlotta
    et al.
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Schön, Karin
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Kalbina, Irina
    Örebro University, School of Science and Technology.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andersson, Sören
    Örebro University Hospital. Sch Sci & Technol, Orebro Life Sci Ctr, Univ Orebro, Orebro, Sweden; Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden .
    Bokarewa, Maria I.
    Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
    Lycke, Nils Y.
    Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
    Feeding transgenic plants that express a tolerogenic fusion protein effectively protects against arthritis2016In: Plant Biotechnology Journal, ISSN 1467-7644, E-ISSN 1467-7652, Vol. 14, no 4, p. 1106-1115Article in journal (Refereed)
    Abstract [en]

    Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated if the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants and in this way induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2q restricted DBA/1 mice to assess the preventive effect on collagen-induced arthritis (CIA). The treatment resulted in fewer mice exhibiting disease and arthritis scores were significantly reduced. Immune suppression was evident in treated mice and serum biomarkers for inflammation as well as anti-collagen IgG responses were reduced. In spleen draining and lymph nodes, CD4+ T cell responses were reduced. Concomitant with a reduced effector T cell activity with lower IFNg, IL-13 and IL-17A production we observed an increase in IL-10 production to recall antigen stimulation in vitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to upregulated IL-10 and regulatory T cell (Treg) functions. The present study shows that edible plants expressing a tolerogen were effective at stimulating CD4 T cell tolerance and in protecting against CIA disease. Our study conveys optimism as to the potential of using edible plants for oral treatment of rheumatoid arthritis.

  • 34.
    Hideg, Éva
    et al.
    Pécs University, Pécs, Hungary.
    Jansen, Marcel A. K.
    University College of Cork, Cork, Ireland.
    Strid, Åke
    Örebro University, School of Science and Technology.
    UV-B exposure, ROS, and stress: inseparable companions or loosely linked associates?2013In: Trends in Plant Science, ISSN 1360-1385, E-ISSN 1878-4372, Vol. 18, no 2, p. 107-115Article in journal (Refereed)
    Abstract [en]

    Ultraviolet-B (UV-B) radiation has long been perceived as a stressor. However, a conceptual U-turn has taken place, and UV-B damage is now considered rare. We question whether UV-stress and UV-B-induced reactive oxygen species (ROS) are still relevant concepts, and if ROS-mediated signaling contributes to UV-B acclimation. Measurements of antioxidants and of antioxidant genes show that both low and high UV-B doses alter ROS metabolism. Yet, there is no evidence that ROS control gene expression under low UV-B. Instead, expression of antioxidant genes is linked to the UV RESISTANCE LOCUS 8 pathway. We hypothesize that low UVB doses cause ‘eustress’ (good stress) and that stimulispecific signaling pathways pre-dispose plants to a state of low alert that includes activation of antioxidant defenses.

  • 35.
    Hideg, Éva
    et al.
    University of Pécs, Pécs, Hungary.
    Strid, Åke
    Örebro University, School of Science and Technology.
    The effects of UV-B on the biochemistry and metabolism of plants2017In: UV-B radiation and plant life: molecular biology to ecology / [ed] Brian R. Jordan, Wallingford, UK: CABI Publishing, 2017, p. 90-110Chapter in book (Refereed)
    Abstract [en]

    This chapter focuses on the effects of UV-B radiation on the biochemistry and metabolism of plants and their underlying mechanisms. Information on the UV-inducible metabolites and protection responses of plants against UV-B radiation are also discussed.

  • 36.
    Hyötyläinen, Tuulia
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Analytical methodologies utilized in the search for chronic disease biomarkers2010In: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 2, no 5, p. 919-923Article in journal (Refereed)
  • 37.
    Hyötyläinen, Tuulia
    et al.
    Steno Diabetes Center, Gentofte, Denmark; Turku Centre for Biotechnology, University of Turku, Turku, Finland; Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.
    Oresic, Matej
    Steno Diabetes Center, Gentofte, Denmark; Turku Centre for Biotechnology, University of Turku, Turku, Finland; Turku Centre for Biotechnology, Åbo Akademi University, Turku, Finland.
    Optimizing the lipidomics workflow for clinical studies: practical considerations2015In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 407, no 17, p. 4973-4993, article id 8633Article, review/survey (Refereed)
    Abstract [en]

    Lipidomics is increasingly being used in clinical research, offering new opportunities for disease prediction and detection. One of the key challenges of clinical applications of lipidomics is the high sensitivity of measured lipid levels to many analytical, physiological, and environmental factors, which therefore must be taken into account when designing the studies. Here we critically discuss the complete clinical lipidomics workflow, including selection of the subjects, the sample type, the sample preprocessing conditions, and the analytical method and methods for data processing. We also review the lipidomics applications which investigate the confounding factors such as age, gender, fasting time, and handling procedures for measuring blood lipid metabolites.

  • 38.
    Hyötyläinen, Tuulia
    et al.
    Steno Diabetes Center, Gentofte, Denmark.
    Oresic, Matej
    Steno Diabetes Center, Gentofte, Denmark; Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Systems biology strategies to study lipidomes in health and disease2014In: Progress in lipid research, ISSN 0163-7827, E-ISSN 1873-2194, Vol. 55, no 1, p. 43-60Article, review/survey (Refereed)
    Abstract [en]

    Lipids are a diverse group of metabolites that have many key biological functions, acting as structural components of cell membranes, energy storage sources and intermediates in signaling pathways. Due to their importance lipids are under tight homeostatic control and exhibit spatial and dynamic complexity at multiple levels. It is thus not surprising that altered lipid metabolism plays important roles in the pathogenesis of most of the common diseases. Lipidomics emerged as a discipline which is dedicated to global study of lipidomes, including pathways and networks of lipids in biological systems. When studying the lipidomes at a systems level, one of the key challenges is how to address the lipid functionality at many physiological levels, from metabolic and signaling pathways to spatial systems such as cellular membranes and lipoprotein particles. Besides the better analytical techniques to study lipids, computational techniques have started to emerge which enable modeling of lipidomes in their spatial and dynamic context. Together, the recent methodological advances in lipidomics have a potential to open novel avenues for predictive and preventive medicine. This review focuses on progress in systems approaches to study lipids in health and disease, with specific emphasis on clinical applications.

  • 39.
    Höfig, Kai Peter
    et al.
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Repsilber, Dirk
    Biomathematics/Bioinformatics group, Gentics and Biometry, Research Institute for the Biology of Farm Animals FBN, Dummerstorf, Germany .
    Branke, Biggi
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Roehle, Anja
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Thorns, Christoph
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Jarutat, Tiantom
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Lenfert, Eva
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Kaehler, Christian
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Feller, Alfred
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    Merz, Hartmut
    Institute for Pathology, UKSH Campus Lübeck, Lübeck, Germany.
    New Application for the LightCycler® 480 System: qPCR-based microRNA-Profiling2007In: Biochemica, ISSN 0946-1310, Vol. 4, p. 7-9Article in journal (Refereed)
  • 40.
    Jacobsen, Marc
    et al.
    Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany; Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals, Genetics and Biometry, Dummerstorf, Germany.
    Kleinsteuber, K
    Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
    Gutschmidt, Andrea
    Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
    Schommer-Leitner, S
    Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
    Black, G
    Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
    Walzl, G
    Division of Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST and NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
    Kaufmann, S H E
    Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
    Suppressor of cytokine signaling-3 is affected in T-cells from tuberculosis TB patients2011In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 17, no 9, p. 1323-31Article in journal (Refereed)
    Abstract [en]

    T-cells and T-cell-derived cytokines are crucial mediators of protection against Mycobacterium tuberculosis infection, but these factors are insufficient as biomarkers for disease susceptibility. In order to define T-cell molecules involved in tuberculosis (TB), we compared gene expression profiles of T-cells from patients with active TB, healthy donors with latent M. tuberculosis infection (LTBIs) and non-infected healthy donors (NIDs) by microarray analysis. Pathway-focused analyses identified a prevalent subset of candidate genes involved in the Janus kinase (JAK)-signal transducer and activator of transcription signalling pathway, including those encoding suppressor of cytokine signalling (SOCS) molecules, in the subset of protection-associated genes. Differential expression was verified by quantitative PCR analysis for the cytokine-inducible SH2-containing protein (CISH), SOCS3, JAK3, interleukin-2 receptor α-chain (IL2RA), and the proto-oncogene serine/threonine protein kinase (PIM1). Classification analyses revealed that this set of molecules was able to discriminate efficiently between T-cells from TB patients and those from LTBIs, and, notably, to achieve optimal discrimination between LTBIs and NIDs. Further characterization by quantitative PCR revealed highly variable candidate gene expression in CD4(+) and CD8(+) T-cells from TB patients and only minor differences between CD4(+) and CD8(+) T-cell subpopulations. These results point to a role of cytokine receptor signalling regulation in T-cells in susceptibility to TB.

  • 41. Johansson, Magnus
    et al.
    Nordlund, S
    Transcription of the glnB and glnA genes in the photosynthetic bacterium Rhodospirillum rubrum1996In: Microbiology, ISSN 1350-0872, E-ISSN 1465-2080, Vol. 142 ( Pt 5), p. 1265-1272Article in journal (Refereed)
    Abstract [en]

    The PII protein, encoded by glnB, has a central role in the control of nitrogen metabolism in nitrogen-fixing prokaryotes. The glnB gene of Rhodospirillum rubrum was isolated and sequenced. The deduced amino acid sequence had very high sequence identity to other PII proteins. The glnA gene, encoding glutamine synthetase, was located 135 bp downstream of glnB and was partially sequenced. glnB is cotranscribed with glnA from a promoter with high similarity to the sigma 54-dependent promoter consensus sequence. A putative sigma 70 promoter was also identified further upstream of glnB. Northern blotting analyses showed that in addition glnA is either transcribed from an unidentified promoter or, more likely, that the glnBA transcript is processed to give the glnA mRNA. The total level of the two transcripts was much higher in nitrogen-fixing cells than in ammonia-grown cells.

  • 42. Johansson, Magnus
    et al.
    Nordlund, S
    Uridylylation of the P(II) protein in the photosynthetic bacterium Rhodospirillum rubrum1997In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 179, no 13, p. 4190-4194Article in journal (Refereed)
    Abstract [en]

    The regulatory protein P(II) has been studied in great detail in enteric bacteria; however, its function in photosynthetic bacteria has not been clearly established. As a number of these bacteria have been shown to regulate nitrogenase activity by a metabolic control system, it is of special interest to establish the role of P(II) in these diazotrophs. In this study, we show that P(II) in Rhodospirillum rubrum is modified in response to the N status in the cell and that addition of ammonium or glutamine leads to demodification. We also provide evidence that P(II) is uridylylated. In addition, we show that not only these compounds but also NAD+ promotes demodification of P(II), which is of particular interest as this pyridine nucleotide has been shown to act as a switch-off effector of nitrogenase. Demodification of P(II) by ammonium or NAD+ did not occur in cultures treated with an inhibitor of glutamine synthetase (methionine sulfoximine), whereas treatment with the glutamate synthase inhibitor 6-diazo-5-oxo-norleucine led to total demodification of P(II) without any other addition. The results indicate that P(II) probably is not directly involved in darkness switch-off of nitrogenase but that a role in ammonium switch-off cannot be excluded.

  • 43.
    Johansson, Reine
    et al.
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Gunnarsson, Lavinia Cicortas
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Ohlin, Mats
    Department of Immunotechnology, Lund University, Lund, Sweden.
    Ohlson, Sten
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar, Sweden.
    Thermostable carbohydrate-binding modules in affinity chromatography2006In: Journal of Molecular Recognition, ISSN 0952-3499, E-ISSN 1099-1352, Vol. 19, no 4, p. 275-281Article in journal (Refereed)
    Abstract [en]

    Affinity chromatography is routinely used mostly on a preparative scale to isolate different biomolecules such as proteins and carbohydrates. To this end a variety of proteins is in common use as ligands. To extend the arsenal of binders intended for separation of carbohydrates, we have explored the use of carbohydrate-binding modules (CBM) in affinity chromatography. The thermostable protein CBM4-2 and two variants (X-6 and A-6) thereof, selected from a newly constructed combinatorial library, were chosen for this study. The CBM4-2 predominantly binds to xylans but also crossreacts with glucose-based oligomers. The two CBM-variants X-6 and A-6 had been selected for binding to xylan and Avicel (a mixture of amorphous and microcrystalline cellulose), respectively. To assess the ability of these proteins to separate carbohydrates, they were immobilized to macroporous microparticulate silica and analyses were conducted at temperatures ranging from 25 to 65 degrees C.

    With the given set of CBM-variants, we were able to separate cello- and xylo-oligomers under isocratic conditions. The affinities of the CBMs for their targets were weak (in the mM-microM range) and by adjusting the column temperature we could optimize peak resolution and chromatographic retention times. The access to thermostable CBM-variants with diverse affinities and selectivities holds promise to be an efficient tool in the field of affinity chromatography for the separation of carbohydrates.

  • 44.
    Kalbin, Georgi
    et al.
    Örebro University, Department of Natural Sciences.
    Hidema, Jun
    Brosché, Mikael
    Kumagai, Tadashi
    Bornman, Janet F.
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    UV-B-induced DNA damage and expression of defence genes under UV-B stress: tissue-specific molecular marker analysis in leaves2001In: Plant, Cell and Environment, ISSN 0140-7791, E-ISSN 1365-3040, Vol. 24, no 9, p. 983-990Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the regulatory effect of ultraviolet-B (UV-B) radiation on a number of key stress response genes found in the epidermis and mesophyll of Pisum sativum L., Argenteum mutant. This mutant was chosen for the ease with which the entire epidermis can be removed from the mesophyll tissue. An additional goal was to explore the potential modifying effect of pre-acclimation of plants to UV-B radiation prior to exposure by UV-B during treatment. Results showed that mRNA accumulation was similar during acute short-term UV-B exposure for chalcone synthase (Chs) and short-chain alcohol dehydrogenase (SadA) in both epidermis and mesophyll. In contrast, the mRNA levels differed considerably between tissues for phenylalanine ammonia lyase, chalcone isomerase and lipid transfer protein. After 24 h incubation in visible light after cessation of UV-B exposure, the regulation of mRNA levels also differed between Chs and SadA, the former showing no expression in the epidermis and the latter none in the mesophyll. Acclimation to low UV-B levels before acute exposures resulted in delayed induction of Chs and SadA. Measurements of UV-B-induced cyclobutane pyrimidine dimers (CPDs) showed a greater formation in epidermis than in mesophyll. In addition, acclimation at low UV-B levels resulted in significantly higher basal levels of CPDs than in non-acclimated plants in both mesophyll and epidermis and also in increased damage in concomitant acute exposures. The lack of correlation between the number of CPDs and levels of transcripts for defence genes, indicates that DNA damage does not control transcription of these genes.

  • 45.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology.
    Engstrand, Lars
    Dept Bacteriol, Swedish Inst Infect Dis Control SMI, Solna, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden; Dept Bacteriol, Swedish Inst Infect Dis Control SMI, Solna, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Expression of Helicobacter pylori TonB Protein in Transgenic Arabidopsis thaliana: toward production of vaccine antigens in plants2010In: Helicobacter, ISSN 1083-4389, E-ISSN 1523-5378, Vol. 15, no 5, p. 430-437Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to produce a recombinant version of the highly antigenic Helicobacter pylori TonB (iron-dependent siderophore transporter protein HP1341) in transgenic plants as a candidate oral vaccine antigen. Materials and Methods: Using Agrobacterium-mediated gene transfer, we introduced three different constructs of the tonB gene into the genome of the model plant Arabidopsis thaliana. We investigated transgene insertion by PCR, produced TonB antibodies for analysis of the production of the recombinant protein in plants, verified the identity of the protein produced by mass spectrometry analysis, and analyzed the number of genetic inserts in the plants by Southern blotting. Results: Three different constructs of the expression cassette (full-length tonB, tonB truncated in the 5' end removing the codons for a transmembrane helix, and the latter construct with codons for the endoplasmic reticulum SEKDEL retention signal added to the 3' end) were used to find the most effective way to express the TonB antigen. Production of TonB protein was detected in plants transformed with each of the constructs, confirmed by both Western blotting and mass spectrometry analysis. No considerable differences in protein expression from the three different constructs were observed. The protein concentration in the plants was at least 0.05% of the total soluble proteins. Conclusions: The Helicobacter pylori TonB protein can be produced in Arabidopsis thaliana plants in a form that is recognizable by rabbit anti-TonB antiserum. These TonB-expressing plants are highly suitable for animal studies of oral adminstration as a route for immunization against Helicobacter infections.

  • 46.
    Kalbina, Irina
    et al.
    Örebro University, School of Science and Technology. Orebro Life Science Center.
    Lagerqvist, Nina
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Moiane, Bélisario
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Eduardo Mondlane University, Maputo, Mozambique.
    Ahlm, Clas
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Örebro Life Science Center, Department of Science and Technology, Örebro University, Örebro, Sweden; Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Falk, Kerstin I.
    Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oraladministration of the transgenic plants2016In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 127, p. 61-67Article in journal (Refereed)
    Abstract [en]

    The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula.The economic impact of this pathogen due to livestock losses, as well as its relevance to public health,underscores the importance of developing effective and easily distributed vaccines. Vaccines that can bedelivered orally are of particular interest.

    Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virusantigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein.Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Westernblotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicityin mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportionof the mice elicited specific IgG antibody responses, as compared to the control animals that were fedwild-type plants and of which none sero-converted.

    Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virusproteins, and that the plants are immunogenic when given orally to mice. These are promising findingsand provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus.

  • 47.
    Kalbina, Irina
    et al.
    Örebro University, Department of Natural Sciences.
    Li, Shaoshan
    Björn, Lars Olof
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Wavelength dependence of expression of UV-B-induced molecular markers in Arabidopsis thalianaManuscript (Other academic)
  • 48.
    Kalbina, Irina
    et al.
    Örebro University, Department of Natural Sciences.
    Li, Shaoshan
    Örebro University, Department of Natural Sciences.
    Kalbin, Georgi
    Örebro University, Department of Natural Sciences.
    Björn, Lars Olof
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Two separate UV-B radiation wavelength regions control expression of different molecular markers in Arabidopsis thaliana2008In: Functional Plant Biology, ISSN 1445-4408, E-ISSN 1445-4416, Vol. 35, no 3, p. 222-227Article in journal (Refereed)
    Abstract [en]

    Fluence-response curves were obtained at nine wavelengths in the interval 280-360 nm for mRNA transcripts of four molecular markers induced by ultraviolet-B (UV-B) radiation in Arabidopsis thaliana: CHS (encoding chalcone synthase), PDX1.3 (encoding an enzyme involved in formation of pyridoxine), MEB5.2 (encoding a protein with unknown function but which is strongly up-regulated by UV-B), and LHCB1*3 (encoding a chlorophyll a/b binding protein). Intact Arabidopsis plants were irradiated for 3h using a high intensity deuterium radiation source and narrow bandwith filters (Kalbin et al. 2005, J. Biochem. Biophys. Meth. 65, 1-12) without supplementary PAR. The results obtained suggest the existence of two distinct UV-B signal responses: one sensitive between 300 and 310 nm and the other sensitive around 280-290 nm. Among the investigated molecular markers, CHS and PDX1.3 were regulated through the chromophore absorbing around 300 nm, whereas MEB5.2 and LHCB1*3 were regulated through the chromophore absorbing at 280-290 nm. The results obtained show that at least two signal transduction pathways exist that regulate gene expression as a result of absorption of UV-B radiation in plants.

  • 49.
    Kalbina, Irina
    et al.
    Örebro University, Department of Natural Sciences.
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    An Arabidopsis mutant responsive to UV-B irradiationManuscript (Other academic)
  • 50.
    Kalbina, Irina
    et al.
    Örebro University, Department of Natural Sciences.
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Supplementary ultraviolet-B irradiation reveals differences in stress responses between Arabidopsis thaliana ecotypes2005Manuscript (preprint) (Other academic)
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