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  • 1.
    Aarseth Larsson, Kim
    Örebro University, School of Science and Technology.
    Inhibition of SIRT1 Alters Apoptotic and Sex Related Genes in Zebrafish (Danio rerio)2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide - dependent deacetylase that belongs to the sirtuin protein family. The protein has been linked to both cancer through its effect on p53 and age related illnesses through its effect on peroxisome proliferator-activated receptor gamma (PPAR-γ). Recent data have shown a correlation between SIRT1, male fertility and spermatogenesis. Because the mechanism of sex differentiation in zebrafish is still not wellunderstood the sirt1 gene is an attractive target to study in order to improve our understanding of this topic. Zebrafish of different age were exposed to various concentrations of EX-527 toinhibit the SIRT1 protein. This was followed by qRT-PCR analysis of apoptotic and sex-related genes. Both apoptotic and sex-related gene expression levels were affected by the exposure. There were differences in genes that were affected, both between the concentrations of EX-527, and between the ages of the exposed zebrafish. The male- specific gene sexdetermining region Y box 9A (sox9a) was down-regulated at both studied EX-527 concentrations in both zebrafish larvae and juveniles. The exposure of the EX-527 resulted in no significant difference in sex-ratio. Further studies are required to describe the pathway for SIRT1 gene regulation in zebrafish.

  • 2.
    Abderhim, Walid Tajeddinn
    Örebro University, School of Science and Technology.
    Morphological Analysis of β-catenin and E-cadherin in Colorectal Cancer2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 3.
    Abuabaid, Hanan
    et al.
    Örebro University, School of Science and Technology.
    Karlsson, Mattias
    Örebro University, School of Science and Technology.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Jass, Jana
    Örebro University, School of Science and Technology.
    Probiotic Lactobacillus rhamnosus alters inflammatory responses of bladder epithelial and macrophage-like cells in co-cultureManuscript (preprint) (Other academic)
  • 4.
    Ahmad, Abrar
    Örebro University, School of Science and Technology.
    Kras and Braf mutation analysis in colon cancer by pyrosequencing2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 5.
    Andersson, Josefin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Utvärdering av Malaria Antigen ELISA kit för diagnostik av malaria vid Christian Medical College and Hospital i Vellore, Indien.: en jämförande studie mellan Quantitative buffy coat och enzyme-linked immunosorbent assays (ELISA) metodik.2006Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Malaria är ett globalt hälsoproblem som orsakar många dödsfall runt om i världen varje år och nästan hälften av jordens befolkning ligger i riskzonen att drabbas av sjukdomen. I Indien drabbas mellan 2-3 miljoner människor varje år och det inträffar omkring 900 dödsfall. Malaria orsakas av Plasmodium sp. som är en protozoe, och det finns fyra olika arter som är patogena för människor, P. vivax, P. ovale, P. falciparium samt P. malariae.

    Vanliga metoder för att diagnostisera malaria är genom tunna och tjocka blodutstryk som färgas till exempel med Giemsa, Fields eller Leishmans färgningsteknik och studeras mikroskopiskt, Quantitative Buffy Coat (QBC), PCR tester, acridinorange färgning samt olika immunologiska tester för detektion av antikroppar eller antigen som till exempel enzyme-linked immunosorbent assays (ELISA) test och dipstick test.

    Syftet med denna studie är att utvärdera om en användning av SD Bio Line Malaria Antigen ELISA kit ger en mer känslig, tillförlitlig, praktisk samt mindre kostsam diagnostikmetod för malaria hos patienter med misstänkt malariainfektion än den nuvarande guldstandardmetoden, QBC tillsammans med blodutstryk, vid Christian Medical College and Hospital i Vellore.

    Patientproverna har i både ELISA testet samt QBC testet tillsammans med utstryk erhållit samma resultat vilket tyder på att SD Bio Line Malaria Antigen ELISA kitet skulle kunna vara en lika bra diagnostikmetod som QBC testet för diagnos av malaria. ELISA kitet har dock fler nackdelar, i jämförelse med QBC testet, så därför är slutsatsen att SD Bio Line Malaria Antigen ELISA kitet inte är en mer lämplig diagnostisk metod för malaria än den som används vid CMCH. Men då ELISA testet ändå ger en säker diagnos, enligt resultatet i studien, kan den vara ett lämpligt test inom något annat användningsområde.

  • 6. Andersson, P. L.
    et al.
    Berg, A. H.
    Bjerselius, R.
    Norrgren, L.
    Olsén, H.
    Olsson, Per-Erik
    Institutionen för Molekylärbiologi, Umeå Universitet.
    Örn, S.
    Tysklind, M.
    Bioaccumulation of selected PCBs in zebrafish, three-spined stickleback, and arctic char after three different routes of exposure2001In: Archives of Environmental Contamination and Toxicology, ISSN 0090-4341, E-ISSN 1432-0703, Vol. 40, no 4, 519-530 p.Article in journal (Refereed)
    Abstract [en]

    The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.

  • 7. Andorf, Sandra
    et al.
    Altmann, T
    Witucka-Wall, H
    Selbig, Joachim
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Molecular network structures in heterozygotes: A systems-biology approach to heterosis2009Conference paper (Refereed)
  • 8.
    Andorf, Sandra
    et al.
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Gärtner, Tanja
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Steinfath, Matthias
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Witucka-Wall, Hanna
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Altmann, Thomas
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Towards systems biology of heterosis: a hypothesis about molecular network structure applied for the Arabidopsis metabolome2009In: EURASIP Journal on Bioinformatics and Systems Biology, ISSN 1687-4145, E-ISSN 1687-4153, 147157Article in journal (Refereed)
    Abstract [en]

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

  • 9.
    Andorf, Sandra
    et al.
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Department of Medicine, Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.
    Meyer, Rhonda C
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Selbig, Joachim
    Bioinformatics Chair, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
    Altmann, Thomas
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Repsilber, Dirk
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Integration of a systems biological network analysis and QTL results for biomass heterosis in Arabidopsis thaliana2012In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 11, e49951Article in journal (Refereed)
    Abstract [en]

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

  • 10. Andorf, Sandra
    et al.
    Repsilber, Dirk
    Institute of Genetics and Biometry, Bioinformatics and Biomathematics Unit, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Molecular network structures in heterozygotes: A systems biological approach to heterosis2009In: Neue Methoden der Biometrie: 55. Biometrisches Kolloquium / [ed] R. Foraita, T. Gerds, L. A. Hothorn, M. Kieser, O. Kuß, U. Munzel, R. Vonk, A. Ziegler, 2009Conference paper (Refereed)
  • 11.
    Andorf, Sandra
    et al.
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Gremany.
    Selbig, Joachim
    University of Potsdam, Potsdam-Golm, Germany.
    Altmann, T
    Leibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany.
    Witucka-Wall, H
    University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Gremany.
    Heterosis in Arabidopsis thaliana: A metabolite network structure approach2010In: 11th Day of the Doktoral Student: abstract; 19 May 2010, Dummerstorf, Dummerstorf, Germany: FBN , 2010, 7-10 p.Conference paper (Refereed)
  • 12.
    Andorf, Sandra
    et al.
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Selbig, Joachim
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Altmann, Thomas
    Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Poos, Kathrin
    University of Applied Sciences Gelsenkirchen, Site Recklinghausen, Recklinghausen, Germany .
    Witucka-Wall, Hanna
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Enriched partial correlations in genome-wide gene expression profiles of hybrids (A. thaliana): a systems biological approach towards the molecular basis of heterosis2010In: Theoretical and Applied Genetics, ISSN 0040-5752, E-ISSN 1432-2242, Vol. 120, no 2, 249-59 p.Article in journal (Refereed)
    Abstract [en]

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

  • 13. Andorf, Sandra
    et al.
    Selbig, Joachim
    Meyer, Rhonda
    Altmann, Thomas
    Repsilber, Dirk
    Integrating a molecular network hypothesis and QTL results for heterosis in Arabidopsis thaliana2010In: Statistical Computings 2010: Abstracts der 42. Arbeitstagung, 2010, Vol. 5Conference paper (Refereed)
  • 14.
    Andrén, O.
    et al.
    Departments of Ecology and Environmental Research, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Barley straw decomposition with varied levels of microbial grazing by Folsomia fimetaria (L.) (Collembola, Isotomidae)1985In: Oecologia, ISSN 0029-8549, E-ISSN 1432-1939, Vol. 68, no 1, 57-62 p.Article in journal (Refereed)
    Abstract [en]

    Folsomia fimetaria (L.) were added (0, 5, 10, 20 animals) to 0.100 g barley straw which had been inoculated 10 days (244 h) earlier with a natural soil microflora. Respiration (CO2 evolution) was monitored continuously. Mass loss, fungal standing crop (total and FDA-active), bacterial and protozoan biomass were estimated 42 days (1,000 h) after microbial inoculation. The degree of surface cover by hyphae was surveyed at regular intervals. No significant differences (P>0.05) were found in respiration, mass loss or microbial biomass, but the density of surface hyphae were reduced by addition of Collembola. Fungal production was low, less than 5% of the estimated microbial production, and could not account for all collembolan growth during incubation. F. fimetaria appeared to consume mainly bacteria and protozoa, and had little impact on carbon mineralization.

  • 15.
    Arinell, Karin
    et al.
    Örebro University, School of Health Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Sahdo, Berolla
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Evans, Alina L.
    Faculty of Forestry and Wildlife Management, Hedmark University College, Campus Evenstad, Norway; Section of Arctic Veterinary Medicine, Norwegian School of Veterinary Science, Tromsø, Norway.
    Arnemo, Jon M.
    Faculty of Forestry and Wildlife Management, Hedmark University College, Campus Evenstad, Norway; Department of Wildlife Fish and Environmental Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Baandrup, Ulrik
    Department of Pathology, Vendsyssel Hospital, Hjørring, Denmark; Faculty of Medical Sciences, Aalborg, Denmark.
    Fröbert, Ole
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Cardiology.
    Brown Bears (Ursus arctos) Seem Resistant to Atherosclerosis -Despite Highly Elevated Plasma Lipids during Hibernation and Active State2012In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 5, no 3, 269-272 p.Article in journal (Refereed)
    Abstract [en]

    Hibernation is an extreme physiological challenge for the brown bear (Ursus arctos) in which metabolism is based mainly on lipids. The study objective was to compare plasma lipids in hibernating and active free-ranging brown bears and relate them to arterial histopathology. Blood was drawn from seven immobilized free-ranging brown bears (three females, 23 years old) during hibernation in February and from the same bears while active in June and analyzed by enzymatic and automated hematology methods within 48 hours of sampling. Left anterior descending coronary arteries and aortic arches from 12 bears (six females, 1.512 years old) killed in hunting were examined by histopathology. Total plasma cholesterol decreased from hibernation to the active period (11.08 +/- 1.04 mmol/L vs. 7.89 +/- 1.96 mmol/L, P= 0.0028) as did triglyceride (3.16 +/- 0.62 mmol/L vs. 1.44 +/- 0.27 mmol/L, P= 0.00012) and LDL cholesterol (4.30 +/- 0.71 mmol/L vs. 2.02 +/- 1.03 mmol/L, P= 0.0075), whereas HDL cholesterol was unchanged. No atherosclerosis, fatty streaks, foam cell infiltration, or inflammation were seen in any arterial samples. Brown bears tolerate elevated cholesterol levels, obesity, physical inactivity, and circulatory slow flow during hibernation without signs of -atherosclerosis. This species might serve as a reverse translational model for atherosclerosis resistance.

  • 16.
    Asghar, Naveed
    et al.
    Södertörn University, School of Natural Science, Technology & Environmental Studies, Huddinge, Sweden .
    Lee, Yi-Ping
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Nilsson, Emma
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Lindqvist, Richard
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Kröger, Andrea
    Helmholtz Centre for Infection Research, Innate Immunity and Infection, Braunschweig, Germany; University of Magdeburg, Institute for Microbiology, Magdeburg, Germany.
    Överby, Anna K.
    Umeå University, Department of Clinical Microbiology, Virology, Umeå, Sweden; Umeå University, The Laboratory for Molecular Medicine Sweden (MIMS), Umeå, Sweden.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 39265Article in journal (Refereed)
    Abstract [en]

    The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Torö-2003 with the wild-type (A)3C(A)6 sequence (Torö-6A) or with a modified (A)3C(A)38 sequence (Torö-38A). Torö-38A replicated poorly compared to Torö-6A in cell culture, but Torö-38A was more virulent than Torö-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.

  • 17.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindblom, Pontus
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Melik, Wessam
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases, Linköping University Hospital, Linköping, Sweden.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Andreassen, Åshild
    Division of Infectious Disease Control, Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
    Lindgren, Per-Eric
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Medical Services, Department of Microbiology, County Hospital Ryhov, Jönköping, Sweden.
    Johansson, Magnus
    Örebro University, School of Medicine, Örebro University, Sweden. School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden; RiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tick-Borne Encephalitis Virus Sequenced Directly from Questing and Blood-Feeding Ticks Reveals Quasispecies Variance2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, e103264Article in journal (Refereed)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 18.
    Asghar, Naveed
    et al.
    Södertörns Högskola, Huddinge, Sweden.
    Wessam, Melik
    Södertörns Högskola, Huddinge, Sweden.
    Lindblom, Pontus
    Linköpings Universitet, Linköping, Sweden.
    Lindgren, Per-Erik
    Linköpings Universitet, Linköping, Sweden.
    Andreassen, Åshild
    Norska folkhälsoinstitutet, Oslo, Norway.
    Johansson, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University, School of Medicine, Örebro University, Sweden.
    Genomic Sequencing of Tick-borne Encephalitis Virus frin Questing and Blood-Feeding Ixodes ricinus2013Conference paper (Other academic)
  • 19.
    Asherson, Philip
    et al.
    MRC SGDP Centre, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, United Kingdom.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Family, twin, and adoption studies of childhood onset psychiatric and neurodevelopmental disorders2016In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 171, no 7, 923-924 p.Article in journal (Refereed)
  • 20.
    Asnake, Solomon
    Örebro University, School of Science and Technology.
    Interaction of brominated flame retardants with the chicken and zebrafish androgen receptors2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The survival of organisms depends on their ability to use different signaling pathways to adapt to the environment. The endocrine system consists of glands that release hormones to the blood stream. Male reproductive functions are regulated by androgens through interactions with the androgen receptor (AR). AR has been characterized in chicken and zebrafish where they use testosterone and 11-ketotestosterone as their primary androgens, respectively. AR function has been disturbed by different endocrine disrupting compounds (EDCs) present in the environment causing detrimental effects on avian and fish species. Brominated flame retardants (BFRs) are a group of EDCs that are ubiquitous in the environment. Molecular modeling techniques using computer simulations such as docking and molecular dynamics are a useful tool in the identification of EDCs. The capacity to test thousands of compounds at once has helped in the early identification of EDCs that interact with AR. Two groups of BFRs, the 1,2-dibromo-4- cyclohexane diastereomers (TBECH) and the compounds synthesized from 2, 4, 6-tribromophenol, allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6- tribromophenyl ether (BATE) and 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE) interact and alter AR activity in human in vitro studies. As models for avian and fish species, chicken and zebrafish were used to test these BFRs. TBECH diastereomers were able to bind to the AR, estrogen receptors and thyroid receptors in the chicken and to the AR in zebrafish. ATE, BATE and DPTE were also able to interact with the chicken AR and zebrafish AR. Activation studies using cell lines showed that TBECH diastereomers acted as agonists to the cAR and zAR while ATE, BATE and DPTE acted as antagonists. The BFRs also altered multiple signaling pathways such as the apoptotic, antiapoptotic, immune, drug metabolizing and DNA methylation systems and in vivo studies resulted in physiological effects on zebrafish.

    List of papers
    1. 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH)-mediated steroid hormone receptor activation and gene regulation in chicken LMH cells
    Open this publication in new window or tab >>1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH)-mediated steroid hormone receptor activation and gene regulation in chicken LMH cells
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    2014 (English)In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 33, no 4, 891-899 p.Article in journal (Refereed) Published
    Abstract [en]

    The incorporation of brominated flame retardants into industrial and household appliances has increased their occurrence in the environment, resulting in deleterious effects on wildlife. With the increasing restraints on available compounds, there has been a shift to using brominated flame retardants that has seen the production of alternative brominated flame retardants such as 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH), which has been detected in the environment. In previous in silico and in vitro studies the authors have shown that TBECH can activate both the human androgen receptor (hAR) and the zebrafish AR (zAR) suggesting that it is a potential endocrine disruptor. The present study was aimed at determining the interaction of TBECH with the chicken AR (cAR). In the present study, TBECH bound to cAR, but in vitro activation assay studies using the chicken LMH cell line showed it had a potency of only 15% compared with testosterone. Sequence difference between ARs from different species may contribute to the different responses to TBECH. Further quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis showed that TBECH interacted with and altered the expression of both thyroid receptors and estrogen receptors. In addition, the qRT-PCR analysis showed that TBECH altered the transcription pattern of genes involved in inflammatory, apoptotic, proliferative, DNA methylation, and drug-metabolizing pathways. This demonstrates that TBECH, apart from activating cAR, can also influence multiple biological pathways in the chicken.

    Place, publisher, year, edition, pages
    Hoboken: Wiley-Blackwell, 2014
    Keyword
    Endocrine disruptor, Diastereomer, Enantiomer, Quantitative polymerase chain reaction (qPCR), Gene regulation
    National Category
    Environmental Sciences
    Research subject
    Enviromental Science; Biology
    Identifiers
    urn:nbn:se:oru:diva-34941 (URN)10.1002/etc.2509 (DOI)000333538700020 ()2-s2.0-84897431931 (Scopus ID)
    Funder
    Swedish Research Council
    Note

    Funding Agency:

    Örebro University

    Available from: 2014-05-05 Created: 2014-05-05 Last updated: 2017-10-17Bibliographically approved
    2. The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    Open this publication in new window or tab >>The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    2013 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 142, 63-72 p.Article in journal (Refereed) Published
    Abstract [en]

    Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been shown to be a potent agonist to the human androgen receptor (AR). However, while it is present in the environment, it is not known if it interacts with AR from aquatic species. The present study was therefore aimed at improving our understanding of how TBECH affects aquatic animals using zebrafish as a model organism. In silica modeling demonstrated that TBECH diastereomers bind to the zebrafish androgen receptor (zAR) and in vitro and in vivo data showed that TBECH has androgenic properties. Deleterious effects of TBECH were studied on embryonic and juvenile zebrafish and qRT-PCR analysis in vitro and in vivo was performed to determine TBECH effects on gene regulation. TBECH was found to delay hatching at 1 mu M and 10 mu M doses while morphological abnormalities and juvenile mortality was observed at 10 mu M. The qRT-PCR analysis showed alterations of multiple genes involved in chondrogenesis (cartilage development), metabolism and stress response. Thus, TBECH induces androgenic activity and has negative effects on zebrafish physiology and therefore its impact on the environment should be carefully monitored. (C) 2013 Elsevier B.V. All rights reserved.

    Keyword
    Androgens, Endocrine, Endocrine disruptor, Gene regulation
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:oru:diva-32902 (URN)10.1016/j.aquatox.2013.07.018 (DOI)000328093900007 ()23958786 (PubMedID)
    Funder
    Knowledge Foundation
    Available from: 2014-01-02 Created: 2014-01-02 Last updated: 2017-10-17Bibliographically approved
    3. The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and alter gene expression in chicken LMH cells
    Open this publication in new window or tab >>The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and alter gene expression in chicken LMH cells
    (English)Manuscript (preprint) (Other academic)
    Keyword
    EDC, Avian, signaling pathways, ATE, BATE, DPTE, TBECH
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:oru:diva-43909 (URN)
    Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-10-17Bibliographically approved
    4. In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish
    Open this publication in new window or tab >>In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Brominated flame retardants, stereoidgenesis, gene regulation, hatch, teratogenesis
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:oru:diva-43911 (URN)
    Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-10-17Bibliographically approved
  • 21.
    Asnake, Solomon
    et al.
    Örebro University, School of Science and Technology.
    Pradhan, Ajay
    Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden.
    Kharlyngdoh, Joubert Banjop
    Örebro University, School of Science and Technology.
    Modig, Carina
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and act as potential endocrine disrupters in chicken LMH cells2015In: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 29, no 8, 1993-2000 p.Article in journal (Refereed)
    Abstract [en]

    Increased exposure of birds to endocrine disrupting compounds has resulted in developmental and reproductive dysfunctions. We have recently identified the flame retardants, ally1-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropy1-2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyI-2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen receptor (AR) and the zebrafish AR. In the present study, we aimed at determining whether these compounds also interact with the chicken AR. In silico modeling studies showed that TBP-AE, TBP-BAE and TBP-DBPE were able to dock into to the chicken AR ligand-binding pocket. In vitro transfection assays revealed that all three brominated compounds acted as chicken AR antagonists, inhibiting testosterone induced AR activation. In addition, qRT-PCR studies confirmed that they act as AR antagonists and demonstrated that they also alter gene expression patterns of apoptotic, anti-apoptotic, drug metabolizing and amino acid transporter genes. These studies, using chicken LMH cells, suggest that TBP-AE, TBP-BAE and TBP-DBPE are potential endocrine disrupters in chicken.

  • 22.
    Asnake, Solomon
    et al.
    Örebro University, School of Science and Technology.
    Pradhan, Ajay
    Örebro University, School of Science and Technology.
    Kharlyngdoh, Joubert Banjop
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and alter gene expression in chicken LMH cellsManuscript (preprint) (Other academic)
  • 23.
    Aydin, Ayhan
    Örebro University, School of Science and Technology.
    Påverkas smaken på höns av foder, genmaterial och tillagningsmetoder?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Få produkter i Sverige innehåller idag höns däremot ökar konsumtionen av ägg. Den ojämna balansen mellan ökad äggproduktion och minskad konsumtion av höna tycks vara en uppåtgående trend. Höns som livsmedel har utgått i det ordinarie sortimentet hos de stora livsmedelskedjorna. Livsmedelsproducenter har slutat använda höns på grund av ”kvalitetsbrister” som att de har fått skört skelett. I och med det kan benflisor komma med i köttet. Huvudsakligen är hönsen avlade för att producera mycket ägg - ett om dagen, i stora grupper. Dessa djur är anpassade för storskalig produktion med många djur på en liten yta. Den separering som skett mellan slaktkycklingar och värphöns med början på 1920-talet kan varit en del av förklaringen med minskad hönskötts konsumtion. Hos äldre djur finns det mer bindväv och fettansamling. Den ökade mängden bindväv gör att konsistensen på köttet uppfattas segare men också saftigare, då fett ansamlas där. Substanserna som finns i fettvävnaden, ger upphov till den karaktäristiska smaken och aromen som finns i köttet. Det blir tydligare vid upphettning. När ett djur blir äldre ökar mängden bindväv och dess tvärbindningar, som både stabiliserar men även blir mer värmetåliga. Desto mer ett djuret rör på sig, blir de röda muskelfibrerna aktiva och bildar en grövre struktur. Åldern tillsammans med rörelse kan också skapa ett mer smakrikt kött men även ett segare kött av större fibrer i bindväven som behöver längre tillagningstid.

    I denna studie undersöktes smak samt textur av foder och genmaterial med två olika tillagningsmetoder, kokning samt sous-vide. En panel utvärderade det utifrån 13 variabler. Där det fanns en tydligast signifikans var skillnaden mellan lår och bröst. Att dela upp höns i bröst och lår/vingar gör att förutsättningarna för en mer exakt tillagning ökar. De variabler som hade en signifikans när en PCA-analys gjordes var: textur: saftighet, fethet; smak: härsken; doft: umami, härsket. När t-test utfördes blev det signifikans på saftighet, fethet, smak av härsket och doften av umami. Variablerna som tydligast skilde sig åt mellan bröst och lår var texturerna, saftighet och fethet. Det var ingen signifikant skillnad mellan genotyperna, tillagning eller foder.

  • 24. Bahr, Adam
    et al.
    Ellström, Magnus
    Akselsson, Cecilia
    Ekblad, Alf
    Örebro University, School of Science and Technology.
    Mikusinska, Anna
    Örebro University, School of Science and Technology.
    Wallander, Håkan
    Growth of ectomycorrhizal fungal mycelium along a Norway spruce forest nitrogen deposition gradient and its effect on nitrogen leakage2013In: Soil Biology and Biochemistry, ISSN 0038-0717, E-ISSN 1879-3428, Vol. 59, 38-48 p.Article in journal (Refereed)
    Abstract [en]

    Almost all boreal and temperate forest tree species live in symbiosis with ectomycorrhizal fungi (EMF); the trees transfer carbon (C) to the fungi in exchange for nutrients and water. Several studies have shown that experimental application of inorganic nitrogen (N) represses production of EMF extramatrical mycelia (EMM), but studies along N deposition gradients are underrepresented. Other environmental variables than N may influence EMM production and in this study we included 29 thoroughly monitored Norway spruce stands from a large geographical region in Sweden in order to evaluate the importance of N deposition on EMM growth and N leaching in a broader context. It was concluded that N deposition was the most important factor controlling EMM production and that the amounts typically deposited in boreal and boreo-nemoral regions can be sufficient to reduce EMM growth. Other factors, such as phosphorus status and pH, were also correlated with EMM production and should be considered when predicting EMM growth and N leaching. We also showed that EMM production substantially contributed to the C sequestration (320 kg ha(-1) yr(-1)), suggesting that it should be included in C cycle modelling. Furthermore, EMF are probably important for the N retention capacity since high N leaching coincided with low EMM growth. However, it was not possible to differentiate between the effects of EMF and the direct effect of N deposition on N leaching in the present study.

  • 25.
    Baker, Laura
    et al.
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Tuvblad, Catherine
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Wang, Pan
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Gomez, Karina
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Bezdjian, Serena
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Niv, Sharon
    Department of Psychology (SGM 501), University of Southern California, Los Angeles, United States.
    Raine, Adrian
    Departments of Criminology and Psychiatry, University of Pennsylvania, Philadelphia, PA, United States .
    The southern california twin register at the University of Southern California: III2013In: Twin Research and Human Genetics, ISSN 1832-4274, Vol. 16, no 1, 336-343 p.Article in journal (Refereed)
  • 26.
    Baker, Laura
    et al.
    University of Southern California, USA.
    Tuvblad, Catherine
    University of Southern California, USA.
    Wang, Pan
    University of Southern California, USA.
    Younan, Diana
    University of Southern California, USA.
    Franklin, Meredith
    University of Southern California, USA.
    Lurman, Fred
    Sonoma Technology, Inc, USA.
    Wu, Jun
    University of California, Irvine College of Health Sciences, USA.
    Chen, Jiu-Chiuan
    University of Southern California, USA.
    The Relationship between IQ and PM2.5: Findings from the University of Southern California Twin Study2016In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 46, no 6, 772-773 p.Article in journal (Refereed)
    Abstract [en]

    We examined the longitudinal relationship between IQ and fine particulate matter (\2.5lm aerodynamic diameters; PM2.5) exposure in urban-dwelling children, using prospective longitudinal data from the USC Twin Study of Risk Factors for Antisocial Behavior (RFAB; Baker et al. 2013). Residential addresses were collected via selfreports. Verbal and Performance IQ during childhood (age 9–10) and young adulthood (age 19–20) were evaluated by the Wechsler Abbreviated Intelligence Scale (Wechsler, 1999) using four subtests: VIQ=Vocabulary Similarities; PIQ=Block Design Matrices. Based on residential addresses and spatiotemporal generalized additive model of local monitoring data for PM2.5, we estimated 1-year average exposure before each assessment. A three-level mixed effects model regressing IQ scores at each assessment on time-varying air pollution exposures, accounting for both within-family (random intercepts) and within-individual (random slopes) was used. PM2.5 exposure had significant adverse effects on PIQ (95 % CI of b:-7.29 to-1.01, p\.05) but not VIQ (95 % CI of b:-4.50 to-1.96). Adverse effects of PM2.5 exposure remained significant after adjusting for age, family SES, sex, race/ethnicity, parental cognitive abilities, neighborhood SES, neighborhood quality and neighborhood greenness; the association was still significant after further adjusting for traffic distance (300 m), temperature, humidity and annual NOx. PM2.5 exposure confers stronger adverse effects on PIQ in low SES families, males, and during pre-adolescence. Our findings reveal social disparities and sexual dimorphism in the adverse PM2.5 exposure effects on PIQ. Baker, L., Tuvblad, C., Wang, P., Gomez, K., Bezdjian, S., Niv, S., & Raine, A. (2013). The Southern California Twin Register at the University of Southern California: III. Twin Research and Human Genetics, 16(1), 336–343; Wechsler, D. (1999). Wechsler Abbreviated Scale of Intelligence (WASI). San Antonio, Texas: Harcourt Assessment.

  • 27.
    Balcha, Ermias Sissay
    Örebro University, School of Science and Technology.
    C10X Polymorphism in the CARD8 gene is Associated with Bacteremia2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 28.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Persson, Katarina
    Örebro University, School of Medical Sciences.
    Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, e0178541Article in journal (Refereed)
    Abstract [en]

    Treatment of urinary tract infections is today a challenge due to the increasing prevalence of multidrug-resistant ESBL-producing uropathogenic Escherichia coli (UPEC). There is an urgent need for new treatment strategies for multidrug-resistant UPEC and preferably with targets that have low potential for development of resistance. Carbon monoxide-releasing molecules (CORMs) are novel and potent antibacterial agents. The present study examines the transcriptomic targets of CORM-2 in a multidrug-resistant ESBL-producing UPEC isolate in response to a single exposure to CORM-2 and after repeated exposure to CORM-2. The bacterial viability and minimal inhibitory concentration (MIC) were also examined after repeated exposure to CORM-2. Microarray analysis revealed that a wide range of processes were affected by CORM-2, including a general trend of down-regulation in energy metabolism and biosynthesis pathways and up-regulation of the SOS response and DNA repair. Several genes involved in virulence (ibpB), antibiotic resistance (marAB, mdtABC) and biofilm formation (bhsA, yfgF) were up-regulated, while some genes involved in virulence (kpsC, fepCEG, entABE), antibiotic resistance (evgA) and biofilm formation (artIP) were down-regulated. Repeated exposure to CORM-2 did not alter the gene expression patterns, the growth inhibitory response to CORM-2 or the MIC values for CORM-2, cefotaxime, ciprofloxacin and trimethoprim. This study identifies several enriched gene ontologies, modified pathways and single genes that are targeted by CORM-2 in a multidrug-resistant UPEC isolate. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the susceptibility to CORM-2 remained after repeated exposure.

  • 29.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kinnunen, Annica
    Univ Örebro, IRiSC, Fac Med & Hlth, Örebro, Sweden.
    Karlsson, Marie
    Univ Örebro, IRiSC, Fac Med & Hlth, Örebro, Sweden.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Lab Med.
    Persson, Katarina
    Örebro University, School of Medicine, Örebro University, Sweden.
    The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide2014In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 14, 65Article in journal (Refereed)
    Abstract [en]

    Background: Nitric oxide (NO) is produced as part of the host immune response to bacterial infections, including urinary tract infections. The enzyme flavohemoglobin, coded by the hmp gene, is involved in protecting bacterial cells from the toxic effects of NO and represents a potentially interesting target for development of novel treatment concepts against resistant uropathogenic bacteria. The aim of the present study was to investigate if the in vitro antibacterial effects of NO can be enhanced by pharmacological modulation of the enzyme flavohemoglobin.

    Results: Four clinical isolates of multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing uropathogenic E. coli were included in the study. It was shown that the NO-donor substance DETA/NO, but not inactivated DETA/NO, caused an initial growth inhibition with regrowth noted after 8 h of exposure. An hmp-deficient strain showed a prolonged growth inhibition in response to DETA/NO compared to the wild type. The imidazole antibiotic miconazole, that has been shown to inhibit bacterial flavohemoglobin activity, prolonged the DETA/NO-evoked growth inhibition. When miconazole was combined with polymyxin B nonapeptide (PMBN), in order to increase the bacterial wall permeability, DETA/NO caused a prolonged bacteriostatic response that lasted for up to 24 h.

    Conclusion: An NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.

  • 30.
    Banjop Kharlyngdoh, Joubert
    Örebro University, School of Science and Technology.
    Modulation of androgen receptor function by brominated flame retardants2015Doctoral thesis, comprehensive summary (Other academic)
    List of papers
    1. Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters
    Open this publication in new window or tab >>Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters
    Show others...
    2015 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 74, 60-70 p.Article in journal (Refereed) Published
    Abstract [en]

    Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions. In the present study we used in silico modeling to determine the interactions of selected BFRs with the human androgen receptor (AR). Three compounds were found to dock into the ligand-binding domain of the human AR and these were further tested using in vitro analysis. Allyl 2,4,6-tribromophenyl ether (ATE), 2-bromoallyl 2,4,6-tribromophenyl ether (BATE) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) were observed to act as AR antagonists. These BFRs have recently been detected in the environment, in house dust and in aquatic animals. The compounds have been detected at high concentrations in both blubber and brain of seals and we therefore also assessed their impact on the expression of L-type amino acid transporter system (LAT) genes, that are needed for amino acid uptake across the blood-brain barrier, as disruption of LAT gene function has been implicated in several brain disorders. The three BFRs down-regulated the expression of AR target genes that encode for prostate specific antigen (PSA), 5. α-reductases and β-microseminoprotein. The potency of PSA inhibition was of the same magnitude as the common prostate cancer drugs, demonstrating that these compounds are strong AR antagonists. Western blot analysis of AR protein showed that ATE, BATE and DPTE decreased the 5. α-dihydrotestosterone-induced AR protein levels, further confirming that these BFRs act as AR antagonists. The transcription of the LAT genes was altered by the three BFRs, indicating an effect on amino-acid uptake across cellular membranes and blood-brain barrier. This study demonstrated that ATE, BATE and DPTE are potent AR antagonists and the alterations in LAT gene transcription suggest that these compounds can affect neuronal functions and should be considered as potential neurotoxic and endocrine disrupting compounds.

    Keyword
    Gene regulation; Human; PSA; LAT
    National Category
    Environmental Sciences
    Research subject
    Biology
    Identifiers
    urn:nbn:se:oru:diva-41508 (URN)10.1016/j.envint.2014.09.002 (DOI)000346681700008 ()25454221 (PubMedID)2-s2.0-84908626070 (Scopus ID)
    Funder
    Knowledge Foundation, 20110183
    Note

    Funding Agency:

    Örebro University J61900

    Available from: 2015-01-14 Created: 2015-01-14 Last updated: 2017-10-17Bibliographically approved
    2. The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    Open this publication in new window or tab >>The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances
    2013 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 142, 63-72 p.Article in journal (Refereed) Published
    Abstract [en]

    Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been shown to be a potent agonist to the human androgen receptor (AR). However, while it is present in the environment, it is not known if it interacts with AR from aquatic species. The present study was therefore aimed at improving our understanding of how TBECH affects aquatic animals using zebrafish as a model organism. In silica modeling demonstrated that TBECH diastereomers bind to the zebrafish androgen receptor (zAR) and in vitro and in vivo data showed that TBECH has androgenic properties. Deleterious effects of TBECH were studied on embryonic and juvenile zebrafish and qRT-PCR analysis in vitro and in vivo was performed to determine TBECH effects on gene regulation. TBECH was found to delay hatching at 1 mu M and 10 mu M doses while morphological abnormalities and juvenile mortality was observed at 10 mu M. The qRT-PCR analysis showed alterations of multiple genes involved in chondrogenesis (cartilage development), metabolism and stress response. Thus, TBECH induces androgenic activity and has negative effects on zebrafish physiology and therefore its impact on the environment should be carefully monitored. (C) 2013 Elsevier B.V. All rights reserved.

    Keyword
    Androgens, Endocrine, Endocrine disruptor, Gene regulation
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:oru:diva-32902 (URN)10.1016/j.aquatox.2013.07.018 (DOI)000328093900007 ()23958786 (PubMedID)
    Funder
    Knowledge Foundation
    Available from: 2014-01-02 Created: 2014-01-02 Last updated: 2017-10-17Bibliographically approved
    3. Androgen receptor mutations associated with prostate cancer lead to differential activation by DBE-DBCH diastereomers
    Open this publication in new window or tab >>Androgen receptor mutations associated with prostate cancer lead to differential activation by DBE-DBCH diastereomers
    (English)Manuscript (preprint) (Other academic)
    Keyword
    steroid hormone receptor, endocrine disruptor, human carcinoma, androgen agonists
    National Category
    Biological Sciences
    Research subject
    Biology
    Identifiers
    urn:nbn:se:oru:diva-44665 (URN)
    Available from: 2015-05-20 Created: 2015-05-20 Last updated: 2017-10-17Bibliographically approved
    4. Combination effects on human cell lines following exposure to brominated flame-retardants that interact with the androgen receptor
    Open this publication in new window or tab >>Combination effects on human cell lines following exposure to brominated flame-retardants that interact with the androgen receptor
    (English)Manuscript (preprint) (Other academic)
    Keyword
    DBE-DBCH/TBECH, TBP-AE/ATE, TBP-BAE/BATE, TBP-DBPE/DPTE, endocrine disruptors, PSA, steroidogenesis
    National Category
    Biological Sciences
    Research subject
    Biology
    Identifiers
    urn:nbn:se:oru:diva-44666 (URN)
    Available from: 2015-05-20 Created: 2015-05-20 Last updated: 2017-10-17Bibliographically approved
  • 31.
    Banjop Kharlyngdoh, Joubert
    et al.
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Combination effects on human cell lines following exposure to brominated flame-retardants that interact with the androgen receptorManuscript (preprint) (Other academic)
  • 32.
    Banjop Kharlyngdoh, Joubert
    et al.
    Örebro University, School of Science and Technology.
    Pradhan, Ajay
    Örebro University, School of Science and Technology.
    Asnake, Solomon
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Androgen receptor mutations associated with prostate cancer lead to differential activation by DBE-DBCH diastereomersManuscript (preprint) (Other academic)
  • 33. Baskar, Sushmitha
    et al.
    Baskar, Ramanathan
    Routh, Joyanto
    Örebro University, School of Science and Technology.
    Biogenic evidences of moonmilk deposition in the Mawmluh cave, Meghalaya, India2011In: Geomicrobiology Journal, ISSN 0149-0451, E-ISSN 1521-0529, Vol. 28, no 3, 252-265 p.Article in journal (Refereed)
    Abstract [en]

    Moonmilk, a microcrystalline secondary cave deposit, actively forms on the floor of Krem Mawmluh - a limestone cave in Meghalaya, Northeastern India. Due to the abundance of micrite and calcified microbial filaments, we hypothesize that these deposits form as a result of ongoing microbial interactions. Consistent with this idea, we report electron microscopic and microbiological evidences for the biological origin of moonmilk in Krem Mawmluh. Scanning electron microscopy indicated abundant calcified microbial filaments, needle calcite, fibre calcites (micro-fibre and nano-fibre calcite crystals), biofilm and microbial filaments in the moonmilk. The total viable culturable microbes showed high population densities for microbes in the moonmilk and moonmilk pool waters. In vitro culture experiments, confirmed the capability of many of the isolated strains to precipitate calcite and some of the identified isolates belonged to the Bacillus sp. and Actinomycetes. These results clearly support the biogenic nature of the deposits.

  • 34.
    Baxter, Charles J
    et al.
    Department of Plant Sciences, University of Oxford, Oxford, United Kingdom.
    Redestig, Henning
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Schauer, Nicolas
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Repsilber, Dirk
    ax-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Patil, Kiran R
    Center for Microbial Biotechnology, BioCentrum Technical University of Denmark, Kongens Lyngby, Denmark.
    Nielsen, Jens
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Selbig, Joachim
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Liu, Junli
    Genetics Programme, Scottish Crop Research Institute, Dundee, United Kingdom .
    Fernie, Alisdair R
    Max-Planck Institute for Molecular Plant Physiology, Potsdam-Golm, Germany.
    Sweetlove, Lee J
    Department of Plant Sciences, University of Oxford, Oxford, United Kingdom.
    The metabolic response of heterotrophic Arabidopsis cells to oxidative stress2007In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 143, no 1, 312-25 p.Article in journal (Refereed)
    Abstract [en]

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

  • 35.
    Bayayibign, Biruhalem Assefa
    Örebro University, School of Science and Technology.
    Effect of oxidative stress on tryptophan and tyrosine uptake in cultured human fibroblasts: the  role of α tocotreinol: Oxidative stress and amino acid uptake2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Aberrant transport of tryptophan and tyrosine is implicated in abnormal dopaminergic and serotoninergic transmissions in psychiatric disorders. Disturbed transport of tyrosine is a repeated finding in cultured fibroblasts from psychiatric patients. The causes for the aberrant transport are not clearly defined yet, but a general membrane dysfunction and altered amino acid transport in psychiatric patients are suggested as major factors. Cellular macromolecules (for example, membrane proteins and lipids) damage associated with oxidative stress are common phenomena in psychiatric patients and antioxidants are proven to be effective in the management of certain psychiatric disorders as therapeutic adjutants. Moreover, oxidative stress has been reported to inhibit the uptake of amino acids in vitro that can be reversed by the application of antioxidants. The aims of the present study were to assess the effect of hydrogen peroxide (H2O2) on tryptophan and tyrosine uptake, and to further investigate the role of α-tocotrienol in counteracting the effect of H2O2 on tryptophan and tyrosine uptake in cultured fibroblasts. Fibroblasts from a healthy control were treated with H2O2, α-tocotrienol and H2O2 and α-tocotrienol together, and the uptake of L-[14C] tyrosine and L-[3H] tryptophan was determined by using the cluster tray technique. Treatment of fibroblasts with H2O2 significantly (P<0.05) inhibited tyrosine uptake (15.4% inhibition), and the inhibition was prevented by the application of α-tocotrienol. The same treatment conditions did not affect the uptake of tryptophan at the specific tryptophan concentration used for the uptake assay in this study. The results of this study suggest that oxidative stress could be a cause for the aberrant tyrosine transport in fibroblasts from different psychiatric patients and provide a potential mechanism of action for antioxidants used in the treatment of psychiatric disorders; further studies are required to understand the role of oxidative stress on amino acid transporters.

  • 36.
    Belew, Yeshiwas Ayalneh
    Örebro University, School of Science and Technology.
    Consequence of Sun Exposure on the Level of Urinary Thymine Dimer and the Modulating Effect of Sunscreen2013Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Solar ultraviolet radiation (UVR) absorbed by the human skin cells can cause DNA lesions and formation of those is linked to development of skin cancer. Cylobutane thymine dimer (T=T) is one of the predominant lesions which is excreted in the urine after repair in skin cells. Urinary T=T can be used as a biomarker of exposure to UVR. The aim of this study was to determine the impact of UVR on urinary T=T levels in individuals before and after one week at the island Tenerife and to compare the protective effect of sunscreen in two groups, i.e. group (A) of 12 persons who had to use sunscreen as instructed and group (B) of 11 persons who were not instructed to use sunscreen. Furthermore, the association between T=T levels and other parameters such as standard erythemal dose, pigment protection factor, time spent outdoors and serum vitamin D level was investigated. Urinary T=T was analysed with the 32P-postlabelling assay. T=T could not be detected in samples collected before going to Tenerife, but after returning from the island the levels were increased in a rage of 27 to 804 fmol/μmol creatinine (mean 140 and 180 fmol/μmol creatinine for group A and B, respectively). There was no significant difference in T=T levels between the two study groups (p = 0.82). The hypothesis was that T=T levels for group B would be higher than for group A and the reason for not finding that is unknown but could simply be due to the low number of participants. No significant correlations were observed between T=T level and other  parameters, except for T=T with time spent outdoors, with a negative correlation which can not be explained. In conclusion, UVR exposure induces DNA damage in exposed humans that is measurable as increased T=T levels in urine.

  • 37.
    Berg, A. H.
    et al.
    Örebro University, School of Science and Technology.
    Westerlund, L.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Regulation of Arctic char (Salvelinus alpinus) egg shell proteins and vitellogenin during reproduction and in response to 17beta-estradiol and cortisol2004In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 135, no 3, 276-285 p.Article in journal (Refereed)
    Abstract [en]

    Estrogens induce both vitellogenin (Vtg) and egg shell (zona pellucida; ZP) protein synthesis in salmonids. However, while Vtg is strictly under estrogenic control, recent reports suggest that additional mechanisms are involved in ZP protein synthesis. During sexual maturation both estrogen and glucocorticoid levels increase in the circulation of female fish. As glucocorticoids have been shown to interfere with Vtg induction in fish we investigated whether cortisol (F) had similar effects on ZP regulation. In the present study we determined both the natural variation in Vtg and ZP during an annual reproductive cycle in female Arctic char (Salvelinus alpinus), and the effect of co-treatment of juvenile Arctic char with 17beta-estradiol (E2) and F. During sexual maturation the expression of Vtg and ZP correlated to plasma levels of E2 and F. Determination of Vtg and ZP protein levels following co-treatment with E2 and F showed that F antagonized E2 induction of Vtg. However, F was observed to potentiate the expression of ZP protein in the same fish. These results indicate that in Arctic char Vtg and ZP proteins are not regulated by the same mechanisms and suggest that ZP protein expression does not necessarily imply exposure to estrogenic compounds alone, and may thus not be ideally suited as a biomarker of exposure to estrogenic compounds.

  • 38.
    Berg, A. Håkan
    et al.
    Örebro University, Department of Natural Sciences.
    Thomas, Peter
    Olsson, Per-Erik
    Örebro University, Department of Natural Sciences.
    Biochemical characterization of the Arctic char (Salvelinus alpinus) ovarian progestin membrane receptor2005In: Reproductive Biology and Endocrinology, ISSN 1477-7827, Vol. 3, 64- p.Article in journal (Refereed)
    Abstract [en]

    Membrane progestin receptors are involved in oocyte maturation in teleosts. However, the maturation-inducing steroid (MIS) does not appear to be conserved among species and several progestins may fulfill this function. So far, complete biochemical characterization has only been performed on a few species. In the present study we have characterized the membrane progestin receptor in Arctic char (Salvelinus alpinus) and show that the 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) receptor also binds several xenobiotics, thus rendering oocyte maturation sensitive to environmental pollutants. We identified a single class of high affinity (Kd, 13.8 +/- 1.1 nM), low capacity (Bmax, 1.6 +/- 0.6 pmol/g ovary) binding sites by saturation and Scatchard analyses. Receptor binding displayed rapid association and dissociation kinetics typical of steroid membrane receptors, with t1/2 s of less than 1 minute. The 17,20beta-P binding also displayed tissue specificity with high, saturable, and specific 17,20beta-P binding detected in ovaries, heart and gills while no specific binding was observed in muscle, brain or liver. Changes in 17,20beta-P binding during oocyte maturation were consistent with its identity as the oocyte MIS membrane receptor. Incubation of fully-grown ovarian follicles with gonadotropin induced oocyte maturation, which was accompanied by a five-fold increase in 17,20beta-P receptor binding. In addition, competition studies with a variety of steroids revealed that receptor binding is highly specific for 17,20beta-P, the likely maturation-inducing steroid (MIS) in Arctic char. The relative-binding affinities of all the other progestogens and steroids tested were less than 5% of that of 17,20beta-P for the receptor. Several ortho, para derivatives of DDT also showed weak binding affinity for the 17,20beta-P receptor supporting the hypothesis that xenobiotics may bind steroid receptors on the oocyte's surface and might thereby interfere with oocyte growth and maturation.

  • 39.
    Berg, Håkan
    et al.
    Örebro University, School of Science and Technology.
    Modig, Carina
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    17beta-estradiol induced vitellogenesis is inhibited by cortisol at the post-transcriptional level in Arctic char (Salvelinus alpinus)2004In: Reproductive biology and endocrinology, ISSN 1477-7827, Vol. 2, 62- p.Article in journal (Refereed)
    Abstract [en]

    This study was performed to investigate stress effects on the synthesis of egg yolk precursor, vitellogenin (Vtg) in Arctic char (Salvelinus alpinus). In particular the effect of cortisol (F) was determined since this stress hormone has been suggested to interfere with vitellogenesis and is upregulated during sexual maturation in teleosts. Arctic char Vtg was purified and polyclonal antibodies were produced in order to develop tools to study regulation of vitellogenesis. The Vtg antibodies were used to develop an enzyme-linked immunosorbent assay. The corresponding Vtg cDNA was cloned from a hepatic cDNA library in order to obtain DNA probes to measure Vtg mRNA expression. Analysis of plasma from juvenile Arctic char, of both sexes, exposed to different steroids showed that production of Vtg was induced in a dose dependent fashion by 17beta-estradiol (E2), estrone and estriol. Apart from estrogens a high dose of F also upregulated Vtg. In addition, F, progesterone (P) and tamoxifen were tested to determine these compounds ability to modulate E2 induced Vtg synthesis at both the mRNA and protein level. Tamoxifen was found to inhibit E2 induced Vtg mRNA and protein upregulation. P did not alter the Vtg induction while F reduced the Vtg protein levels without affecting the Vtg mRNA levels. Furthermore the inhibition of Vtg protein was found to be dose dependent. Thus, the inhibitory effect of F on Vtg appears to be mediated at the post-transcriptional level.

  • 40.
    Berg, Håkan
    et al.
    Örebro University, School of Science and Technology. Marine Science Institute, University of Texas at Austin, United States .
    Rice, Charles
    Department of Biology, Clemson University, United States .
    Rahman, Saydur
    Marine Science Institute, University of Texas at Austin, United States .
    Dong, Jing
    Marine Science Institute, University of Texas at Austin, United States .
    Thomas, Peter
    Marine Science Institute, University of Texas at Austin, United States .
    Identification and characterization of membrane androgen receptors in the ZIP9 zinc transporter subfamily: I. Discovery in female Atlantic croaker and evidence ZIP9 mediates testosterone-induced apoptosis of ovarian follicle cells2014In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 155, no 11, 4237-4249 p.Article in journal (Refereed)
    Abstract [en]

    Rapid, cell surface-initiated, pregenomic androgen actions have been described in various vertebrate cells, but the receptors mediating these actions remain unidentified.We report here cloning and expression of a cDNA from Atlantic croaker (Micropogonias undulatus) ovaries encoding a 33kDa, 7-transmembrane protein with binding and signaling characteristics of a membrane androgen receptor (mAR) that is unrelated to any previously described steroid receptor. Instead croaker mAR has 81–93 % amino acid sequence identity with zinc transporter ZIP9 (SLC39A9) subfamily members, indicating it is a ZIP9 protein. Croaker ZIP9 is expressed in gonadal tissues and in brain, and is upregulated in the ovary by reproductive hormones. ZIP9 protein is localized to plasma membranes of croaker granulosa cells and human breast cancer (SKBR-3) cells stably transfected with ZIP9. Recombinant croaker ZIP9 has a high affinity (Kd 12.7 nM), limited capacity (Bmax 2.8nM/mgprotein), displaceable, single binding site specific for androgens, characteristic of steroid receptors. Testosterone activates a stimulatory G protein coupled to ZIP9, resulting in increased cAMP production. Testosterone promotes serum starvation-induced cell death and apoptosis in transfected cells and in croaker ovarian follicle cells that is associated with rapid increases in intracellular free zinc concentrations, suggesting an involvement of zinc in this nonclassical androgen action to promote apoptosis. These responses to testosterone are abrogated by treatment with ZIP9 siRNA. The results provide the first evidence that zinc transporter proteins can function as specific steroid membrane receptors and indicate a previously unrecognized signaling pathway mediated by steroid receptors involving alterations in intracellular zinc.

  • 41.
    Berg, Håkan
    et al.
    Örebro University, School of Science and Technology.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Liimatta, Harri
    Örebro University, School of Science and Technology.
    Hoffmann, Erik
    Karlsson, Johnny
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Characterization of antibodies for quantitative determination of spiggin protein levels in male and female three-spined stickleback (Gasterosteus aculeatus)2009In: Reproductive Biology and Endocrinology, ISSN 1477-7827, E-ISSN 1477-7827, Vol. 7, no 1, 46Article in journal (Refereed)
    Abstract [en]

    Spiggin is an adhesive glycoprotein produced in the kidney of sticklebacks during the breeding season and is subsequently secreted into the urinary bladder from where it is employed for nest building. Since the production of the protein has been shown to be under androgenic control, spiggin has been suggested to be a useful biomarker for androgenic substances in the environment. In this study, two polyclonal spiggin antibodies based on synthetic peptides and one polyclonal antibody directed against native spiggin have been characterized. The antibodies ability to identify spiggin was investigated by quantitative immunoassay. For both peptide antibodies the quantification range was determined to be between 1 and 80 ng spiggin and determination of renal spiggin levels from immature and mature males displayed a 15-fold increase in total spiggin content of the kidney resulting in a 6-fold increase in male kidney weight due to hypertrophy. The kidney somatic index (KSI) was found to correlate well with the total renal spiggin content and therefore it appears that KSI in sticklebacks could be used as an initial method to identify substances displaying androgenic effects. Furthermore, western blot analysis revealed that the polyclonal antibodies recognize different spiggin isoforms and that spiggin can be detected in the urinary bladder and kidney of both males and female sticklebacks. In order to develop a quantitative detection method for native spiggin it is necessary to produce a standard that can be used in a bioassay. Due to the adhesive and polymerization characteristics of spiggin the protein is difficult to use as a standard in bioassays. So far spiggin has been shown to exist in at least 14 isoforms, all of which contain polymerization domains. To overcome the solubility problem we have produced recombinant spiggin gamma, with only one polymerization domain, that can be expressed in E. coli. Western blot analysis demonstrated that the polyclonal antibodies were able to detect recombinant spiggin gamma protein in bacterial cell lysate, suggesting that it may be developed into a useful source of standard spiggin to be used for quantitative determination of androgen induced spiggin production in sticklebacks.

  • 42. Berglund, S. Linnea
    et al.
    Agren, Goran I.
    Ekblad, Alf
    Örebro University, School of Science and Technology.
    Carbon and nitrogen transfer in leaf litter mixtures2013In: Soil Biology and Biochemistry, ISSN 0038-0717, E-ISSN 1879-3428, Vol. 57, 341-348 p.Article in journal (Refereed)
    Abstract [en]

    The decomposition rate of litter mixtures can differ from that expected on the basis of the decomposition rate of the individual components. This difference may be linked to nitrogen (N) transfer from high-N to low-N components. Transfer of N is probably also associated with transfer of C, but the extent and direction of this C transfer are unknown. This study examined transfer and loss in laboratory microcosms of C and N from two mixed litter species (Scots pine, Pinus sylvestris L and maize, Zea mays L), which have natural isotopic differences in C-13. Half the material was N-15-labelled and the plants were fertilised or unfertilised. Substantial bidirectional transfer of C and N occurred between the litters, with net transfer of C from pine to maize litter and net transfer of N from high-N to low-N litter. Mixtures of fertilised and unfertilised plant litter showed higher than expected C losses and net transfer of N. Mixtures with litters from the same fertilisation treatment had small or insignificant net transfer of N and their C losses did not differ from values estimated using the decomposition rates of the pure litters.

  • 43.
    Berndtson, Eva
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Engvall, Anders
    Department of Epizootiology, National Veterinary Institute, Uppsala, Sweden.
    Experimental colonization of mice with Campylobacter jejuni1994In: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 41, no 1-2, 183-188 p.Article in journal (Refereed)
    Abstract [en]

    The ability of one human and two chicken strains of Campylobacter jejuni to colonise and survive in three different strains of laboratory mice (NMRI, CBA and C57-Black) was studied. Mice were inoculated orally with Campylobacter jejuni and faeces samples were cultured at regular intervals during the following months. The length of colonisation of mice differed between mouse strains but also between Campylobacter strains. The mouse strain C57-Black was not colonised with C. jejuni to the same degree as the other mouse strains. It is concluded that mice can become colonised for prolonged periods and that they may act as reservoirs of Campylobacter for other species.

  • 44.
    Beuchat, L. R.
    et al.
    Center for Food Safety and Department of Food Science and Technology, University of Georgia, Griffin, GA, USA.
    Frändberg, E.
    Biology Division, National Food Administration, Uppsala, Sweden.
    Deak, T.
    Center for Food Safety and Department of Food Science and Technology, University of Georgia, Griffin, GA, USA; Department of Microbiology and Biotechnology, Szent Istvan University, Budapest, Hungary.
    Alzamora, S. M.
    Pabellon de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
    Chen, J.
    Center for Food Safety and Department of Food Science and Technology, University of Georgia, Griffin, GA, USA.
    Guerrero, S.
    Pabellon de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, Argentina.
    López-Malo, A.
    Departmento de Ingenieria Quimica y Alimentos, Universidad de la Americas-Puebla, Sta. Catarina Martir, Puebla, Mexico.
    Ohlsson, I.
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Olsen, M.
    Biology Division, National Food Administration, Uppsala, Sweden.
    Peinado, J. M.
    Departmento de Microbiologia, Facultad de Biologia, Universidad Completense de Madrid, Madrid, Spain.
    Schnürer, Johan
    Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    de Siloniz, M. I.
    Departmento de Microbiologia, Facultad de Biologia, Universidad Completense de Madrid, Madrid, Spain.
    Tornai-Lehoczki, J.
    National Collection of Agricultural and Industrial Microorganisms, Szent Istvan University, Budapest, Hungary.
    Performance of mycological media in enumerating desiccated food spoilage yeasts: an interlaboratory study2001In: International Journal of Food Microbiology, ISSN 0168-1605, E-ISSN 1879-3460, Vol. 70, no 1-2, 89-96 p.Article in journal (Refereed)
    Abstract [en]

    Dichloran 18% glycerol agar (DG18) was originally formulated to enumerate nonfastidious xerophilic moulds in foods containing rapidly growing Eurotium species. Some laboratories are now using DG18 as a general purpose medium for enumerating yeasts and moulds, although its performance in recovering yeasts from dry foods has not been evaluated. An interlaboratory study compared DG18 with dichloran rose bengal chloramphenicol agar (DRBC), plate count agar supplemented with chloramphenicol (PCAC), tryptone glucose yeast extract chloramphenicol agar (TGYC), acidified potato dextrose agar (APDA), and orange serum agar (OSA) for their suitability to enumerate 14 species of lyophilized yeasts. The coefficient of variation for among-laboratories repeatability within yeast was 1.39% and reproducibility of counts among laboratories was 7.1%. The order of performance of media for recovering yeasts was TGYC > PCAC = OSA > APDA > DRBC > DG18. A second study was done to determine the combined effects of storage time and temperature on viability of yeasts and suitability of media for recovery. Higher viability was retained at - 18 degreesC than at 5 degreesC or 25 degreesC for up to 42 weeks, although the difference in mean counts of yeasts stored at - 18 degreesC and 25 degreesC was only 0.78 log(10) cfu/ml of rehydrated suspension. TGYC was equal to PCAC and superior to the other four media in recovering yeasts stored at - 18 degreesC, 5 degreesC, or 25 degreesC for up to 42 weeks. Results from both the interlaboratory study and the storage study support the use of TGYC for enumerating desiccated yeasts. DG18 is not recommended as a general purpose medium for recovering yeasts from a desiccated condition.

  • 45.
    Björk, Emelie
    Örebro University, School of Science and Technology.
    Isolation and Identification of Lactic Acid Bacteria in Certain Traditional Fermented Swedish Food2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 46.
    Björk, Robert G.
    et al.
    Örebro University, School of Science and Technology. Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Ernfors, Maria
    Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Sikström, Ulf
    Forestry Res Inst Sweden Skogforsk, Uppsala, Sweden.
    Nilsson, Mats B.
    Swedish Univ Agr Sci SLU, Dept Forest Ecol & Management, Umea, Sweden.
    Andersson, Mats X.
    Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Rutting, Tobias
    Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Klemedtsson, Leif
    Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Contrasting effects of wood ash application on microbial community structure, biomass and processes in drained forested peatlands2010In: FEMS Microbiology Ecology, ISSN 0168-6496, E-ISSN 1574-6941, Vol. 73, no 3, 550-562 p.Article in journal (Refereed)
    Abstract [en]

    The effects of wood ash application on soil microbial processes were investigated in three drained forested peatlands, which differed in nutrient status and time since application. Measured variables included the concentrations of soil elements and phospholipid fatty acids (PLFAs), net nitrogen (N) mineralization, nitrification and denitrification enzyme activity, potential methane (CH(4)) oxidation, CH(4) production and microbial respiration kinetics. Wood ash application had a considerable influence on soil element concentrations. This mirrored a decrease in the majority of the microbial biomarkers by more than one-third in the two oligotrophic peatlands, although the microbial community composition was not altered. The decreases in PLFAs coincided with reduced net ammonification and net N mineralization. Other measured variables did not change systematically as a result of wood ash application. No significant changes in microbial biomass or processes were found in the mesotrophic peatland, possibly because too little time (1 year) had elapsed since the wood ash application. This study suggests that oligotrophic peatlands can be substantially affected by wood ash for a period of at least 4 years after application. However, within 25 years of the wood ash application, the microbial biomass seemed to have recovered or adapted to enhanced element concentrations in the soil.

  • 47. 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, 431-442 p.Article 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.

  • 48.
    Björkbom, Carina
    et al.
    Laboratory of Aquatic Pathobiology, Environmental and Marine Biology, Department of Biosciences, Åbo Akademi University, Turku, Finland.
    Mustamäki, Noora
    Laboratory of Aquatic Pathobiology, Environmental and Marine Biology, Department of Biosciences, Åbo Akademi University, Turku, Finland.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Katsiadaki, Ioanna
    Cefas Weymouth Laboratory, Weymouth, United Kingdom .
    Wiklund, Tom
    Laboratory of Aquatic Pathobiology, Environmental and Marine Biology, Department of Biosciences, Åbo Akademi University, Turku, Finland.
    Assessment of reproductive biomarkers in three-spined stickleback (Gasterosteus aculeatus) from sewage effluent recipients2013In: Environmental Toxicology, ISSN 1520-4081, E-ISSN 1522-7278, Vol. 28, no 4, 229-237 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine the occurrence of endocrine disruption close to sewage treatment plant effluent discharges along the Finnish Baltic Sea coast using a set of reproductive biomarkers present in adult three-spined stickleback (Gasterosteus aculeatus). Possible variation and sensitivity of the biomarkers during an entire reproductive period were also examined. The analysis of vitellogenin (VTG) for estrogenic activity and spiggin for androgenic activity, together with histopathological analysis indicated that sticklebacks were exposed to estrogenic loads sufficient to cause inappropriate production of VTG and to disrupt normal testicular structure in adult male sticklebacks. No androgenic disruption was observed. The results emphasize the need of a combination of several reproductive biomarkers in fish and repeated sampling for the detection of potential endocrine modulating substances under field condition

  • 49.
    Björkman, Mats P.
    et al.
    Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Morgner, Elke
    Univ Tromso, Fac Biosci Fisheries & Econ, Dept Arctic & Marine Biol, N-9037 Tromso, Norway; Univ Ctr Svalbard, Dept Arctic Biol, Longyearbyen, Norway.
    Cooper, Elisabeth J.
    Univ Tromso, Fac Biosci Fisheries & Econ, Dept Arctic & Marine Biol, N-9037 Tromso, Norway.
    Elberling, Bo
    Univ Ctr Svalbard, Longyearbyen, Norway; Univ Copenhagen, Dept Geog & Geol, DK-1350 Copenhagen, Denmark.
    Klemedtsson, Leif
    Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Björk, Robert G.
    Örebro University, School of Science and Technology. Univ Gothenburg, Dept Plant & Environm Sci, SE-40530 Gothenburg, Sweden.
    Winter carbon dioxide effluxes from Arctic ecosystems: an overview and comparison of methodologies2010In: Global Biogeochemical Cycles, ISSN 0886-6236, E-ISSN 1944-9224, Vol. 24, GB3010- p.Article in journal (Refereed)
    Abstract [en]

    The winter CO(2) efflux from subnivean environments is an important component of annual C budgets in Arctic ecosystems and consequently makes prediction and estimations of winter processes as well as incorporations of these processes into existing models important. Several methods have been used for estimating winter CO(2) effluxes involving different assumptions about the snowpack, all aiming to quantify CO(2) production. Here, four different methods are compared and discussed: (1) measurements with a chamber on the snow surface, F(snow), (2) chamber measurements directly on the soil, F(soil), after snow removal, (3) diffusion measurements, F(2-point), within the snowpack, and (4) a trace gas technique, F(SF6), with multiple gas sampling within the snowpack. According to measurements collected from shallow and deep snow cover in High Arctic Svalbard and subarctic Sweden during the winter of 2007-2008, the four methods differ by up to two orders of magnitude in their estimates of total winter emissions. The highest mean winter CO(2) effluxes, 7.7-216.8 mg CO(2) m(-2) h(-1), were observed using F(soil) and the lowest values, 0.8-12.6 mg CO(2) m(-2) h(-1), using F(SF6). The F(snow) and F(2-point) methods were both within the lower range, 2.1-15.1 and 6.8-11.2 mg CO(2) m(-2) h(-1), respectively. These differences result not only from using contrasting methods but also from the differences in the assumptions within the methods when quantifying CO(2) production and effluxes to the atmosphere. Because snow can act as a barrier to CO(2), F(soil) is assumed to measure soil production, whereas F(SF6), F(snow), and F(2-point) are considered better approaches for quantifying exchange processes between the soil, snow, and the atmosphere. This study indicates that estimates of winter CO(2) emissions may vary more as a result of the method used than as a result of the actual variation in soil CO(2) production or release. This is a major concern, especially when CO(2) efflux data are used in climate models or in carbon budget calculations, thus highlighting the need for further development and validation of accurate and appropriate techniques.

  • 50.
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Environmental Medicine, Karolinska Institutet Stockholm, Stockholm.
    Diverse microbial exposure: Consequences for vaccine development2012In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 30, no 29, 4336-4340 p.Article, review/survey (Refereed)
    Abstract [en]

    Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.

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