To Örebro University

oru.seÖrebro University Publications
Change search
Refine search result
1234567 1 - 50 of 1175
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 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.

    Download full text (pdf)
    fulltext
  • 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.
    Ahlberg, Emelie
    et al.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Martí, Magalí
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Govindaraj, Dhanapal
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Severin, Elisabet
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Allergy Center, Linköping University Hospital, Linköping, Sweden.
    Duchén, Karel
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Allergy Center, Linköping University Hospital, Linköping, Sweden.
    Jenmalm, Maria C.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Tingö, Lina
    Örebro University, School of Medical Sciences. Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children2023In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 34, no 4, article id e13952Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The immunomodulatory capacity of breast milk may partially be mediated by microRNAs (miRNA), small RNA molecules that regulate gene expression on a post-transcriptional level and are hypothesized to be involved in modulation of immunological pathways. Here, we evaluate the expression of immune-related miRNAs in breast milk after pre- and postnatal supplementation with Limosilactobacillus reuteri and omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), and the association to infant regulatory T cell (Treg) frequencies.

    METHODS: One-hundred and twenty women included in a double-blind, randomized, placebo-controlled allergy intervention trial received L. reuteri and/or ω-3 PUFAs daily from gestational week 20. Using Taqman qPCR, 24 miRNAs were analyzed from breast milk obtained at birth (colostrum) and after 3 months (mature milk) of lactation. The proportion of activated and resting Treg cells were analyzed in infant blood using flow cytometry at 6, 12, and 24 months.

    RESULTS: Relative expression changed significantly over the lactation period for most of the miRNAs; however, the expression was not significantly influenced by any of the supplements. Colostrum miR-181a-3p correlated with resting Treg cell frequencies at 6 months. Colostrum miR-148a-3p and let-7d-3p correlated with the frequencies of activated Treg cells at 24 months, as did mature milk miR-181a-3p and miR-181c-3p.

    CONCLUSION: Maternal supplementation with L. reuteri and ω-3 PUFAs did not significantly affect the relative miRNA expression in breast milk. Interestingly, some of the miRNAs correlate with Treg subpopulations in the breastfed children, supporting the hypothesis that breast milk miRNAs could be important in infant immune regulation. TRIAL REGISTRATION: ClinicalTrials.gov-ID: NCT01542970.

  • 5.
    Ahle, Charlotte M.
    et al.
    Beiersdorf AG, Research & Development, Front End Innovation, Hamburg, Germany; Department of Microbiology and Biotechnology, University of Hamburg, Hamburg, Germany.
    Stødkilde, Kristian
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Afshar, Mastaneh
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Poehlein, Anja
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
    Ogilvie, Lesley A.
    Max Planck Institute for Molecular Genetics, Berlin, Germany.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Hüpeden, Jennifer
    Beiersdorf AG, Research & Development, Front End Innovation, Hamburg, Germany.
    Brüggemann, Holger
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Staphylococcus saccharolyticus: An Overlooked Human Skin Colonizer2020In: Microorganisms, E-ISSN 2076-2607, Vol. 8, no 8, article id E1105Article in journal (Refereed)
    Abstract [en]

    Coagulase-negative staphylococcal species constitute an important part of the human skin microbiota. In particular, facultative anaerobic species such as Staphylococcus epidermidis and Staphylococcus capitis can be found on the skin of virtually every human being. Here, we applied a culture-independent amplicon sequencing approach to identify staphylococcal species on the skin of healthy human individuals. While S. epidermidis and S. capitis were found as primary residents of back skin, surprisingly, the third most abundant member was Staphylococcus saccharolyticus, a relatively unstudied species. A search of skin metagenomic datasets detected sequences identical to the genome of S. saccharolyticus in diverse skin sites, including the back, forehead, and elbow pit. Although described as a slow-growing anaerobic species, a re-evaluation of its growth behavior showed that S. saccharolyticus can grow under oxic conditions, and, in particular, in a CO2-rich atmosphere. We argue here that S. saccharolyticus was largely overlooked in previous culture-dependent and -independent studies, due to its requirement for fastidious growth conditions and the lack of reference genome sequences, respectively. Future studies are needed to unravel the microbiology and host-interacting properties of S. saccharolyticus and its role as a prevalent skin colonizer.

  • 6.
    Ahlman, B.
    et al.
    Department of Surgery, Karolinska Hospital, Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Persson, B.
    cDepartment of Radiology, Karolinska Hospital, Stockholm, Sweden.
    Bindslev, L.
    Department of Anesthesiology and Intensive Care, Karolinska Hospital, Department of Anesthesiology and Intensive Care, St Göran's Hospital, Stockholm, Sweden.
    Wernerman, J.
    Metabolic Research Laboratory, St Göran's Hospital, Stockholm, Sweden.
    Intestinal amino acid content in critically ill patients1995In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 19, no 4, p. 272-278Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    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
  • 8.
    Ain, Noor Ul
    et al.
    School of Biological Sciences, University of the Punjab, Lahore, Pakistan; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Baroncelli, Marta
    Center for Molecular Medicine and Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Costantini, Alice
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Ishaq, Tayyaba
    School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
    Taylan, Fulya
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Ola
    Örebro University, School of Medical Sciences. Center for Molecular Medicine and Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Örebro University Hospital, Örebro, Sweden.
    Mäkitie, Outi
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Children's Hospital, University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland.
    Naz, Sadaf
    School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
    Novel form of rhizomelic skeletal dysplasia associated with a homozygous variant in GNPNAT12021In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 58, no 5, p. 351-356Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies exploring molecular mechanisms underlying congenital skeletal disorders have revealed novel regulators of skeletal homeostasis and shown protein glycosylation to play an important role.

    OBJECTIVE: To identify the genetic cause of rhizomelic skeletal dysplasia in a consanguineous Pakistani family.

    METHODS: Clinical investigations were carried out for four affected individuals in the recruited family. Whole genome sequencing (WGS) was completed using DNA from two affected and two unaffected individuals from the family. Sequencing data were processed, filtered and analysed. In silico analyses were performed to predict the effects of the candidate variant on the protein structure and function. Small interfering RNAs (siRNAs) were used to study the effect of Gnpnat1 gene knockdown in primary rat chondrocytes.

    RESULTS: The patients presented with short stature due to extreme shortening of the proximal segments of the limbs. Radiographs of one individual showed hip dysplasia and severe platyspondyly. WGS data analyses identified a homozygous missense variant c.226G>A; p.(Glu76Lys) in GNPNAT1, segregating with the disease. Glucosamine 6-phosphate N-acetyltransferase, encoded by the highly conserved gene GNPNAT1, is one of the enzymes required for synthesis of uridine diphosphate N-acetylglucosamine, which participates in protein glycosylation. Knockdown of Gnpnat1 by siRNAs decreased cellular proliferation and expression of chondrocyte differentiation markers collagen type 2 and alkaline phosphatase, indicating that Gnpnat1 is important for growth plate chondrocyte proliferation and differentiation.

    CONCLUSIONS: This study describes a novel severe skeletal dysplasia associated with a biallelic, variant in GNPNAT1. Our data suggest that GNPNAT1 is important for growth plate chondrogenesis.

  • 9.
    Albet-Torres, Nuria
    et al.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden .
    Gunnarsson, Anders
    Chalmers University of Technology, Dept. of Applied Physics, Gothenburg, Sweden .
    Persson, Malin
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden .
    Balaz, Martina
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden .
    Höök, Fredrik
    Chalmers University of Technology, Dept. of Applied Physics, Gothenburg, Sweden .
    Månsson, Alf
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden .
    Molecular motors on lipid bilayers and silicon dioxide: different driving forces for adsorption2010In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 6, no 14, p. 3211-3219Article in journal (Refereed)
    Abstract [en]

    Understanding how different types of interactions govern adsorption of the myosin motor fragment heavy meromyosin (HMM) onto different substrates is important in functional studies of actomyosin and for the development of motor powered lab-on-a-chip applications. In this study, we have combined in vitro motility assays and quartz crystal microbalance with dissipation (QCM-D) monitoring to investigate the underlying adsorption mechanisms of HMM onto supported lipid bilayers in comparison with pure and silanized SiO2. The QCM-D results, combined with data showing actin transportation by HMM adsorbed onto positively charged supported lipid bilayers, suggest reversible HMM surface adsorption via the negatively charged coiled-coil tail region. In contrast, the QCM-D data for HMM adsorption onto negatively charged lipids support a model according to which HMM adsorbs onto negatively charged surfaces largely via the positively charged actin binding regions. Adsorption studies at low (30-65 mM) and high (185-245 mM) ionic strengths onto piranha cleaned SiO2 surfaces (contact angle < 20 degrees) support this general model. However, unlike the situation for charged lipids, rinsing in high ionic strength solution caused only partial HMM desorption from SiO2, without restoration of actin propulsion by the remaining HMM molecules. This suggests that mechanisms other than electrostatic interactions are involved in the tethering of HMM heads to SiO2 surfaces. An expanded model for HMM adsorption is formulated on the basis of the data and the potential of the results for nanotechnological applications of actomyosin is discussed.

  • 10.
    Alfaro-Moreno, Ernesto
    et al.
    Örebro University, School of Science and Technology.
    Quintana-Belmares, R.
    Instituto Nacional de Cancerologia, Investigacion Basica, Mexico City, Mexico.
    Montiel-Davalos, A.
    Instituto Nacional de Cancerologia, Investigacion Basica, Mexico City, Mexico.
    Gustafsson, A.
    Örebro University, Man-Technology-Environment Research Center, Örebro, Sweden.
    Miranda, J.
    Universidad Nacional Autonoma de Mexico, Instituto de Fisica, Mexico City, Mexico.
    Lopez-Marure, R.
    Instituto Nacional de Cardiologia, Investigacion, Mexico City, Mexico.
    Rosas-Perez, I.
    Universidad Nacional Autonoma de Mexico, Centro de Ciencias de la Atmosfera, Mexico City, Mexico.
    Expression of receptors for adhesion molecules in monocytes exposed to urban particulate matter is independent of size and composition of the particles2019In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 314, no Suppl., p. S232-S233Article in journal (Other academic)
  • 11.
    Alfonso, Sébastien
    et al.
    Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France; UMR MARBEC, Ifremer, IRD, UM2, CNRS, Laboratoire Adaptation et Adaptabilités des Animaux et des Systèmes, Route de Maguelone, F-34250, Palavas-les-Flots, France.
    Blanc, Mélanie
    Örebro University, School of Science and Technology. Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France.
    Joassard, Lucette
    Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France.
    Keiter, Steffen
    Örebro University, School of Science and Technology.
    Munschy, Catherine
    Ifremer, Laboratoire Biogéochimie des Contaminants Organiques, Rue de l'Ile d'Yeu, BP 21105, F-44311, Nantes, Cedex 3, France.
    Loizeau, Véronique
    Ifremer, Laboratoire Biogéochimie des Contaminants Organiques, ZI Pointe du Diable, CS 10070, F-29280, Plouzané, France.
    Bégout, Marie-Laure
    Ifremer, Laboratoire Ressources Halieutiques, Place Gaby Coll, F-17137, L'Houmeau, France.
    Cousin, Xavier
    UMR MARBEC, Ifremer, IRD, UM2, CNRS, Laboratoire Adaptation et Adaptabilités des Animaux et des Systèmes, Route de Maguelone, F-34250, Palavas-les-Flots, France; Inra, UMR GABI, Inra, AgroParisTech, Domaine de Vilvert, Batiment 231, F-78350 Jouy-en-Josas, France.
    Examining multi- and transgenerational behavioral and molecular alterations resulting from parental exposure to an environmental PCB and PBDE mixture2019In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 208, p. 29-38Article in journal (Refereed)
    Abstract [en]

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants extensively used during the 20th century and still present in aquatic environments despite their ban. Effects of exposure to these compounds over generations are poorly documented. Therefore, our aims were to characterize behavioral responses and underlying molecular mechanisms in zebrafish exposed to an environmentally relevant mixture of PCBs and PBDEs as well as in four unexposed offspring generations. Zebrafish (F0) were chronically exposed from the first meal onward to a diet spiked with a mixture containing 22 PCB and 7 PBDE congeners in proportions and concentrations reflecting environmental situations (ΣPCBs = 1991 and ΣPBDEs = 411 ng/g). Four offspring generations (F1 to F4) were obtained from this F0 and were not further exposed. Behavior was assessed at both larval and adult stages. Mechanisms related to behavioral defects (habenula maturation and c-fos transcription) and methylation (dnmts transcription) were monitored in larvae. Exposed adult F0 as well as F1 and F3 adults displayed no behavioral change while F2 expressed anxiety-like behavior. Larval behavior was also disrupted, i.e. hyperactive after light to dark transition in F1 or hypoactive in F2, F3 and F4. Behavioral disruptions may be related to defect in habenula maturation (observed in F1) and change in c-fos transcription (observed in F1 and F2). Transcription of the gene encoding DNA methyltransferase (dnmt3ba) was also modified in all generations. Our results lead us to hypothesize that chronic dietary exposure to an environmentally relevant mixture of PCB and PBDE triggers multigenerational and transgenerational molecular and behavioral disruptions in a vertebrate model.

  • 12.
    Alijagic, Andi
    et al.
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Gaglio, Daniela
    SYSBIO.IT, Centre of Systems Biology, University of Milano-Bicocca, Milano, Italy; Istituto di Bioimmagini e Fisiologia Molecolare (IBFM), Consiglio Nazionale delle Ricerche, Segrate, Milano, Italy.
    Napodano, Elisabetta
    SYSBIO.IT, Centre of Systems Biology, University of Milano-Bicocca, Milano, Italy.
    Russo, Roberta
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Costa, Caterina
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Benada, Oldřich
    Institute of Microbiology of The Czech Academy of Sciences, Prague, Czechia.
    Kofroňová, Olga
    Institute of Microbiology of The Czech Academy of Sciences, Prague, Czechia.
    Pinsino, Annalisa
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Titanium dioxide nanoparticles temporarily influence the sea urchin immunological state suppressing inflammatory-relate gene transcription and boosting antioxidant metabolic activity2020In: Journal of Hazardous Materials, ISSN 0304-3894, E-ISSN 1873-3336, Vol. 384, article id 121389Article in journal (Refereed)
    Abstract [en]

    Titanium dioxide nanoparticles (TiO2NPs) are revolutionizing biomedicine due to their potential application as diagnostic and therapeutic agents. However, the TiO2NP immune-compatibility remains an open issue, even for ethical reasons. In this work, we investigated the immunomodulatory effects of TiO2NPs in an emergent proxy to human non-mammalian model for in vitro basic and translational immunology: the sea urchin Paracentrotus lividus. To highlight on the new insights into the evolutionarily conserved intracellular signaling and metabolism pathways involved in immune-TiO2NP recognition/interaction we applied a wide-ranging approach, including electron microscopy, biochemistry, transcriptomics and metabolomics. Findings highlight that TiO2NPs interact with immune cells suppressing the expression of genes encoding for proteins involved in immune response and apoptosis (e.g. NF-κB, FGFR2, JUN, MAPK14, FAS, VEGFR, Casp8), and boosting the immune cell antioxidant metabolic activity (e.g. pentose phosphate, cysteine-methionine, glycine-serine metabolism pathways). TiO2NP uptake was circumscribed to phagosomes/phagolysosomes, depicting harmless vesicular internalization. Our findings underlined that under TiO2NP-exposure sea urchin innate immune system is able to control inflammatory signaling, excite antioxidant metabolic activity and acquire immunological tolerance, providing a new level of understanding of the TiO2NP immune-compatibility that could be useful for the development in Nano medicines. 

  • 13.
    Alves, Marina Amaral
    et al.
    Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Lamichhane, Santosh
    Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Dickens, Alex
    Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    McGlinchey, Aidan J
    Örebro University, School of Medical Sciences.
    Ribeiro, Henrique C.
    Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Sen, Partho
    Örebro University, School of Medical Sciences. Örebro University Hospital. Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Wei, Fang
    Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan, P. R. China.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
    Systems biology approaches to study lipidomes in health and disease2021In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1866, no 2, article id 158857Article, review/survey (Refereed)
    Abstract [en]

    Lipids have many important biological roles, such as energy storage sources, structural components of plasma membranes and as intermediates in metabolic and signaling pathways. Lipid metabolism is under tight homeostatic control, exhibiting spatial and dynamic complexity at multiple levels. Consequently, lipid-related disturbances play important roles in the pathogenesis of most of the common diseases. Lipidomics, defined as the study of lipidomes in biological systems, has emerged as a rapidly-growing field. Due to the chemical and functional diversity of lipids, the application of a systems biology approach is essential if one is to address lipid functionality at different physiological levels. In parallel with analytical advances to measure lipids in biological matrices, the field of computational lipidomics has been rapidly advancing, enabling modeling of lipidomes in their pathway, spatial and dynamic contexts. This review focuses on recent progress in systems biology approaches to study lipids in health and disease, with specific emphasis on methodological advances and biomedical applications.

  • 14.
    Andersson, Anneli
    et al.
    Örebro University, School of Medical Sciences.
    Tuvblad, Catherine
    Örebro University, School of Law, Psychology and Social Work. University of Southern California, Department of Psychology, Los Angeles CA, USA.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Chen, Qi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Genetic overlap between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms: a systematic review and meta-analysis2018In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 48, no 6, p. 455-456Article in journal (Other academic)
    Abstract [en]

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder (Wilens, Biederman & Spencer 2002) and affects approximately 5% of children (Polanczyk, de Lima, Horta, Biederman & Rohde 2007). About half of those diagnosed in childhood continue to have the diagnosis and symptoms in adulthood (Kessler et al. 2006). The co-occurrence of ADHD with other psychiatric disorder symptoms (Burt et al. 2001; Cole et al. 2009; Polderman et al. 2014) has been suggested to be partly explained by a shared genetic vulnerability (Polderman et al. 2014). However, the strength of the genetic overlap is currently unclear. Also, no study has examined whether the genetic correlations differs between age groups (childhood versus adulthood), by rater (self-report, other informant, combined (parent-teacher, parent-twin, teacher-twin)), or by type of psychiatric disorder symptoms (externalizing, internalizing, neu-rodevelopmental). To address this gap, we conducted a systematic literature search to identify relevant twin studies, in PubMed, PsycINFO, and EMBASE. A total of 31 articles were identified and included in the present study. The pooled estimates showed that the comorbidity between ADHD and diverse psychiatric disorder symptoms were explained by shared genetic effectsrg= 0.50 (0.43–0.56). A similar shared genetic overlap between ADHD and psychiatric disorder symptoms was observed in both childhood rg= 0.51(0.42–0.61) and adulthood rg= 0.47 (0.40–0.53). Similar results werealso found for self-reports rg= 0.49 (0.42–0.55), other informants rg= 0.50 (0.40–0.60), and combined raters rg= 0.51 (0.30–0.69). Further, the strength of the genetic correlations of ADHD with the externalizing rg= 0.49 (0.39–0.59), internalizing rg= 0.55 (0.40–0.68) and neurodevelopmental rg= 0.47 (0.40–0.53) spectrums were similar in magnitude. These findings emphasize the presence of a shared genetic liability between ADHD and externalizing, internalizing and neurodevelopmental disorder symptoms, independent of age and rater.

    References

    Burt, S. A., Krueger, R. F., McGue, M., Iacono, W. G. (2001).Sources of covariation among attention-deficit/hyperactivity disorder,oppositional defiant disorder, and conduct disorder: the importance ofshared environment.Journal of Abnormal Psychology, 4, 516–525.

    Cole, J., Ball, H. A., Martin, N. C., Scourfield, J., McGuffin, P.(2009). Genetic overlap between measures of hyperactivity/inatten-tion and mood in children and adolescents.J Am Acad Child AdolescPsychiatry48, 1094–1101.

    Kessler, R. C., Adler, L., Barkley, R., Biederman, J., Conners, C.K., Demler, O., Faraone, S. V., Greenhill, L. L., Howes, M. J., Secnik,K., Spencer, T., Ustun, T. B., Walters, E. E., Zaslavsky, A. M. (2006).The prevalence and correlates of adult ADHD in the United States:results from the National Comorbidity Survey Replication.Am JPsychiatry, 163, 716–723.

    Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., Rohde,L. A. (2007). The worldwide prevalence of ADHD: a systematicreview and metaregression analysis.Am J Psychiatry, 164, 942-8.

    Polderman, T. J., Hoekstra, R. A., Posthuma, D., Larsson, H.(2014). The co-occurrence of autistic and ADHD dimensions inadults: an etiological study in 17,770 twins.Transl Psychiatry2014;4: e435.

    Wilens, T. E., Biederman, J., Spencer, T. J. (2002). Attentiondeficit/hyperactivity disorder across the lifespan.Annual Review Med53:113–131.

  • 15.
    Andersson, Anton
    Örebro University, School of Science and Technology.
    Identification of DDX3 inhibitors: selection and validation of 17 compounds2020Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Dead box helicase 3, DDX3, is a potential drug target for treatment of many forms of cancer. DDX3 is involved in the B-catenin/wnt pathway by inactivating the destruction complex. Overexpression of DDX3 inactivates the destruction complex leading to unregulated cytosolic B-catenin levels. Elevated cytosolic B-catenin levels leads to over activation of the wnt target genes, which is associated with cell growth and proliferation. DDX3Y has also been identified as a possible inducer of male brain sex differentiation. A microarray of the brain of rat embryo before any effect of gonadal or adrenal hormones (E12) showed increased concentration DDX3Y in males, a fold change of 1552,15. This raises the hypothesis that DDX3Y affects brain sex masculinization. The purpose of this study is to generate inhibitors for DDX3 so further analysis can be done. 18 candidates were selected from a hit list generated from a virtual screening of the DDX3Y protein. Reduction of cell amount was used as an indicator of DDX3 inhibition. HepG2 cells were manually counted after being exposed to concentrations between 0,1µM and 10µM for 120-hours. 7 compounds had significantly reduced the cell amount when exposed to 10µM compared to their control. Compound 5, 14, 15 and 16 had reduced cell amount to below 46% of their control when exposed with 10µM. Compound 15 had 6% cell amount when exposed to 10µM, which is similar to the positive control (RK-33). RK-33 had reduced cell amount to 10% when exposed to 10µM. Given my results I argue that the next step to properly compare compound 15 and RK-33 would be to determine that compound 15 acts through the wnt/B-catenin pathway. That can be done with reporter assay for TCF-activity. Determining the DDX3X/DDX3Y binding ratio is detrimental for progression in brain sex differentiation research. Which could be done by using silencing RNAs for DDX3X and comparing those proliferation rates to the ones of this study. 

  • 16.
    Andersson, Henrik
    et al.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Andersson, Blanka
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Eklund, Daniel
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Ngoh, Eyler
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Persson, Alexander
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Svensson, Kristoffer
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Lerm, Maria
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Blomgran, Robert
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Stendahl, Olle
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 7, article id e101514Article in journal (Refereed)
    Abstract [en]

    Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.

  • 17.
    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.

    Download full text (pdf)
    FULLTEXT01
  • 18.
    Andersson, M. R.
    et al.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Samyn, Dieter R.
    Örebro University, School of Medical Sciences. Örebro University Hospital. School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
    Persson, B. L.
    School of Natural Sciences, Linnaeus University, Kalmar, Sweden; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Belgium; Department of Molecular Microbiology, Leuven-Heverlee, Flanders, Belgium.
    Mutational analysis of conserved glutamic acids of Pho89, a Saccharomyces cerevisiae high-affinity inorganic phosphate:Na + symporter2012In: Biologia, ISSN 0006-3088, E-ISSN 1336-9563, Vol. 67, no 6, p. 1056-1061Article in journal (Refereed)
    Abstract [en]

    In Saccharomyces cerevisiae, the high-affinity phosphate transport system comprises the Pho84 and Pho89 permeases. The Pho89 permease catalyzes import of inorganic phosphate in a symport manner by utilizing Na + ions as co-solute. We have addressed the functional importance of two glutamic acid residues at positions 55 and 491. Both residues are highly conserved amongst members of the inorganic phosphate transporter (PiT) family, which might be an indication of functional importance. Moreover, both residues have been shown to be of critical importance in the hPit2 transporter. We have created site-directed mutations of both E55 and E491 to lysine and glutamine. We observed that in all four cases there is a dramatic impact on the transport activity, and thus it seems that they indeed are of functional importance. Following these observations, we addressed the membrane topology of this protein by using several prediction programs. TOPCONS predicts a 7-5 transmembrane segment organization, which is the most concise topology as compared to the hPiT2 transporter. By understanding the functionality of these residues, we are able to correlate the Pho89 topology to that of the hPiT2, and can now further analyze residues which might play a role in the transport activity. © 2012 Versita Warsaw and Springer-Verlag Wien.

  • 19.
    Andersson, Magdalena
    et al.
    Örebro University, School of Science and Technology.
    Sundberg, Bodil
    Örebro University, School of Science and Technology.
    Ottander, Christina
    Umeå universitet.
    Förundrans roll för elevers meningsskapande om evolutionära processer2022Conference paper (Refereed)
    Abstract [sv]

    Filosofer såväl som forskare har länge hävdat att förundran är en nyckel till elevers intresse och engagemang i skolans NO-undervisning. Trots detta finns det i nuläget mycket få empiriska studier som beskriver lärares arbete med att ge plats för förundran i skolans NO-undervisning.

    Syftet med denna studie är att undersöka hur elevers förundran kan studeras i klassrumssituationer samt om, och hur, elevers uttryck för förundran kan kopplas till deras meningsskapande om ett planerat lärandemål.

    I studien har forskare och en NO-lärare (årskurs 7) samarbetat för att utforma evolutionsundervisning med plats för elevers förundran. Följande forskningsfrågor fokuseras:

    1. På vilka sätt kan lärare ge plats för förundran i samband med evolutionsundervisning?
    2. Hur påverkar undervisning, med plats för förundran, elevers möjligheter för meningsskapande om evolutionära processer och begrepp kopplade till dessa?

    Empirin består av 45 individuella skriftliga elevreflektioner och transkriberade ljudinspelningar från 6 parvisa elevintervjuer. Elevernas reflektioner analyserades i två steg. Steg ett fokuserade på hur eleverna uttryckte förundran i relation till frågan Vad brukar du förundras över? Steg två på vad de förundrats över i evolutionsundervisningen. Elevintervjuerna analyserades med fokus på elevernas meningsskapande om evolutionära processer.

    Resultaten visar att eleverna ger uttryck för förundran kopplat till variation, mångfald, evolutionära tidsaspekter och samspel mellan organismer och livsmiljö. Elevernas förundran skiljer sig kvalitativt inom ett spänningsfält mellan nyfikenhetsbaserad förundran och kontemplativ förundran. Samtidigt visar elevintervjuerna att eleverna fortfarande, efter sex veckor av undervisning, kämpar med att integrera vetenskapliga begrepp från evolutionsteorin med sitt eget meningsskapande om processerna.

    Download full text (pdf)
    Abstrakt
  • 20. 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, p. 519-530Article 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.

  • 21.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    CHIMERIC MOMP ANTIGEN2015Patent (Other (popular science, discussion, etc.))
    Download full text (pdf)
    Patent
  • 22.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Chimeric MOMP antigen2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.

    Download full text (pdf)
    Patent
  • 23. 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)
  • 24.
    Andorf, Sandra
    et al.
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Gärtner, Tanja
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Steinfath, Matthias
    Institute for Biochemistry and Biology, University of Potsdam, Potsdam-Golm, Germany.
    Witucka-Wall, Hanna
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Altmann, Thomas
    Institute for Genetics, University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Bioinformatics and Biomathematics Group, Genetics and Biometry Unit, Research Institute for the Biology of Farm Animals (FBN), Dummersdorf, Germany.
    Towards systems biology of heterosis: a hypothesis about molecular network structure applied for the Arabidopsis metabolome2009In: EURASIP Journal on Bioinformatics and Systems Biology, ISSN 1687-4145, E-ISSN 1687-4153, article id 147157Article in journal (Refereed)
    Abstract [en]

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

  • 25.
    Andorf, Sandra
    et al.
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany; Department of Medicine, Institute for Biostatistics and Informatics in Medicine and Ageing Research, University of Rostock, Rostock, Germany.
    Meyer, Rhonda C
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Selbig, Joachim
    Bioinformatics Chair, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
    Altmann, Thomas
    Department of Molecular Genetics, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Repsilber, Dirk
    Department Genetics and Biometry, Bioinformatics and Biomathematics Group, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
    Integration of a systems biological network analysis and QTL results for biomass heterosis in Arabidopsis thaliana2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 11, article id e49951Article in journal (Refereed)
    Abstract [en]

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

  • 26. 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)
  • 27.
    Andorf, Sandra
    et al.
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
    Selbig, Joachim
    University of Potsdam, Potsdam-Golm, Germany.
    Altmann, T
    Leibniz Institute of Plant Genetics and Crop Plant Research, Gatersleben, Germany.
    Witucka-Wall, H
    University of Potsdam, Potsdam-Golm, Germany.
    Repsilber, Dirk
    Leibniz Institute for Farm Animal Biology, Dummerstorf, Gremany.
    Heterosis in Arabidopsis thaliana: A metabolite network structure approach2010In: 11th Day of the Doktoral Student: abstract; 19 May 2010, Dummerstorf, Dummerstorf, Germany: FBN , 2010, p. 7-10Conference paper (Refereed)
  • 28.
    Andorf, Sandra
    et al.
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Selbig, Joachim
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Altmann, Thomas
    Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.
    Poos, Kathrin
    University of Applied Sciences Gelsenkirchen Site Recklinghausen, Recklinghausen, Germany .
    Witucka-Wall, Hanna
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Repsilber, Dirk
    Research Institute for the Biology of Farm Animals (FBN), Dummerstorf, Germany.
    Enriched partial correlations in genome-wide gene expression profiles of hybrids (A. thaliana): a systems biological approach towards the molecular basis of heterosis2010In: Theoretical and Applied Genetics, ISSN 0040-5752, E-ISSN 1432-2242, Vol. 120, no 2, p. 249-59Article in journal (Refereed)
    Abstract [en]

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

  • 29. 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)
  • 30.
    Andraos, R.
    et al.
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Södergren, A.L.
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Öllinger, K.
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Department of Clinical and Experimental medicine, Linköping University, Linköping, Sweden.
    Reactive oxygen species enhance generation of subpopulations of procoagulant platelets2014Conference paper (Refereed)
  • 31.
    Andraos, R.
    et al.
    Linköping University, Linköping, Sweden.
    Södergren, A.L.
    Linköping University, Linköping, Sweden.
    Öllinger, K.
    Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Linköping University, Linköping, Sweden.
    Reactive oxygen species enhance generation of subpopulations of procoagulant platelets2014Conference paper (Refereed)
  • 32.
    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, p. 57-62Article 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.

  • 33.
    Anjum, Muna F
    et al.
    Department of Bacteriology, Animal and Plant Health Agency, Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, UK.
    Schmitt, Heike
    Centre for Zoonoses and Environmental Microbiology - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands.
    Börjesson, Stefan
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden; Department of Microbiology, Public Health Agency of Sweden, 171 82 Solna, Sweden.
    Berendonk, Thomas U
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden Present address: Department of Microbiology, Public Health Agency of Sweden, 171 82 Solna, Sweden.
    The potential of using E. coli as an indicator for the surveillance of antimicrobial resistance (AMR) in the environment2021In: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 64, p. 152-158Article, review/survey (Refereed)
    Abstract [en]

    To understand the dynamics of antimicrobial resistance (AMR), in a One-Health perspective, surveillance play an important role. Monitoring systems already exist in the human health and livestock sectors, but there are no environmental monitoring programs. Therefore there is an urgent need to initiate environmental AMR monitoring programs nationally and globally, which will complement existing systems in different sectors. However, environmental programs should not only identify anthropogenic influences and levels of AMR, but they should also allow for identification of transmissions to and from human and animal populations. In the current review we therefore propose using antimicrobial resistant Escherichia coli as indicators for monitoring occurrence and levels of AMR in the environment, including wildlife.

  • 34.
    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, 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, 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, Örebro University Hospital, Örebro, Sweden.
    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, p. 269-272Article 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.

  • 35.
    Aronson, D.
    et al.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Wojtaszewski, J.
    Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark.
    Thorell, A.
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Nygren, J.
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Zangen, A.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    Richter, E. A.
    Copenhagen Muscle Research Center, August Krogh Institute, University of Copenhagen, Copenhagen, Denmark.
    Ljungqvist, Olle
    Department of Surgery, Karolinska Hospital and Institute, Stockholm, Sweden.
    Fielding, R. A.
    Department of Health Sciences, Sargent Coll. All. Hlth. Professions, Boston University, Boston, MA , United States.
    Goodyear, L. J.
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Joslin Diabetes Center, One Joslin Place, Boston, MA, United States.
    Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle1998In: American Journal of Physiology, ISSN 0002-9513, E-ISSN 2163-5773, Vol. 275, no 2, p. C555-C561Article in journal (Refereed)
    Abstract [en]

    The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing.

  • 36.
    Arvidsson, A. K.
    et al.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Rupp, E.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Nånberg, Eewa
    Department of Pathology, University Hospital, Uppsala, Sweden.
    Downward, J.
    Signal Transduction Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
    Rönnstrand, L.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Wennström, S.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Schlessinger, J.
    Department of Pharmacology, New York University Medical Center, New York, NY, USA .
    Heldin, C. H.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Claesson-Welsh, L.
    Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
    Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation1994In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 14, no 10, p. 6715-6726Article in journal (Refereed)
    Abstract [en]

    Ligand stimulation of the platelet-derived growth factor (PDGF) beta-receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation of the intracellular part of the receptor. The autophosphorylated tyrosine residues mediate interactions with downstream signal transduction molecules and thereby initiate different signalling pathways. A pathway leading to activation of the GTP-binding protein Ras involves the adaptor molecule GRB2. Here we show that Tyr-716, a novel autophosphorylation site in the PDGF beta-receptor kinase insert, mediates direct binding of GRB2 in vitro and in vivo. In a panel of mutant PDGF beta-receptors, in which Tyr-716 and the previously known autophosphorylation sites were individually mutated, only PDGFR beta Y716F failed to bind GRB2. Furthermore, a synthetic phosphorylated peptide containing Tyr-716 bound GRB2, and this peptide specifically interrupted the interaction between GRB2 and the wild-type receptor. In addition, the Y716(P) peptide significantly decreased the amount of GTP bound to Ras in response to PDGF in permeabilized fibroblasts as well as in porcine aortic endothelial cells expressing transfected PDGF beta-receptors. The mutant PDGFR beta Y716F still mediated activation of mitogen-activated protein kinases and an increased DNA synthesis in response to PDGF, indicating that multiple signal transduction pathways transduce mitogenic signals from the activated PDGF beta-receptor.

  • 37.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Gunaltay, Sezin
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Tran, Pham Tue Hung
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Höglund, Urban
    Adlego Biomedical AB, Uppsala, Sweden.
    Johansson, Christer
    Academy of Quality Pharm Science and BiQ Pharma AB, Södertälje, Sweden.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sällberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    DNA launched suicidal flaviviruses as therapeutic vaccine candidates2018Conference paper (Refereed)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. The relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect interventions with high efficiency. We aim to develop therapeutic vaccine candidates against HBV, HCV and HDV using DNA based subgenomic flavivirus replicons as a delivery system. Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), or Kunjinvirus (KUNV) replicon with firefly luciferase geneas a reporter were expressed and characterized in cell culture studies. WNV and KUNV replicons showed significantly higher replication compared to their respective negative controls with unfunctional viral RNA dependent RNA polymerase. KUNV and WNV replicons were chosen for cloning the HCV or HB/DV vaccine candidate gene by replacing luciferasegene. Owing to the self-replicating trait of the flavivirus subgenomic replicons, Western blotting demonstrated that the antigen expression by KUNV and WNV replicons was several folds higher than the positive control. These results suggest that DNA based KUNV and WNV replicons may function as carriers for the hepatitis vaccine candidate genes, and these replicons are currently used for in vivostudies in animal models.

  • 38.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden .
    Lee, Yi-Ping
    Department of Clinical Microbiology, Virology,Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Nilsson, Emma
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Kröger, Andrea
    Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany; Institute for Microbiology, University of Magdeburg, Magdeburg, Germany.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, 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, E-ISSN 2045-2322, Vol. 6, article id 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.

  • 39.
    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, E-ISSN 1932-6203, Vol. 9, no 7, article id 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.

  • 40.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Maravelia, Panagiota
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tran, Pham Tue Hung
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Pasetto, Anna
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlen, Gustaf
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Höglund, Urban
    Adlego Biomedical AB, Uppsala, Sweden.
    Johansson, Christer
    Academy of Quality Pharm Science and BiQ Pharma AB, Södertälje, Sweden.
    Sällberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses2019Conference paper (Refereed)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. Chronic infections with the hepatitis C virus (HCV) can be effectively cured by antivirals. However, as cured patients can be re-infected they lack protective immune responses. In addition, the relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect vaccines with high efficiency to control and possibly eradicate Hepatitis viruses globally. The vaccine should induce either, or both, neutralizing antibodies and protective T cell responses. We therefore have developed DNA based flavivirus replicons as a potent delivery system that effectively prime HCV-specific T cell responses. We generated suicidal subgenomic DNA replicons of Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), and Kunjinvirus (KUNV) expressing either a fusion protein between the HCV NS3/4A and a stork hepatitis B virus core or a vaccine candidate gene of HB/DV. Transfection experiments showed that the antigen expression by KUNV and WNV replicons was several folds higher than the antigen expression by standard DNA plasmid with CMV promoter. The immunogenicity of three suicidal flaviviral DNA replicons expressing HCV NS3/4A was tested in mice and compared to HCV NS3/4A expression by the standard DNA plasmid. The KUNV-HCV replicon was the best replicon-based immunogen with respect to priming of HCV NS3/4A-specific T cells as determined by ELISpot, dextramer staining, and polyfunctionality. Importantly, a mutant KUNV-HCV immunogen lacking replication failed to induce immune responses. Thus, the newly developed KUNV-based suicidal DNA launched replicon vaccine for HCV is a highly attractive candidate as a prophylactic vaccine against chronic hepatitis C. In addition, we are currently testing the immunogenicity of KUNV-HB/DV replicon in mice.

  • 41.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Paulsen, Katrine M.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Pedersen, Benedikte N.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Bø-Granquist, Erik G.
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Vikse, Rose
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Stuen, Snorre
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Andersson, Sören
    Folkhälsomyndigheten, Public Health Agency of Sweden, Solna, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andreassen, Åshild K.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Transient Expression of Flavivirus Structural Proteins in Nicotiana benthamiana 2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 10, article id 1667Article in journal (Refereed)
    Abstract [en]

    Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment availa-ble, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural pro-teins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection. 

    Download full text (pdf)
    Publisher's fulltext
    Download (pdf)
    bilaga
  • 42.
    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)
  • 43.
    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, p. 923-924Article in journal (Refereed)
  • 44.
    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
    Show others...
    2014 (English)In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 33, no 4, p. 891-899Article 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
    Keywords
    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: 2017-12-05Bibliographically 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, p. 63-72Article 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.

    Keywords
    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)2-s2.0-84882783290 (Scopus ID)
    Funder
    Knowledge Foundation
    Available from: 2014-01-02 Created: 2014-01-02 Last updated: 2023-12-08Bibliographically 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)
    Keywords
    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)
    Keywords
    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
    Download (pdf)
    Spikblad
    Download (pdf)
    Cover
  • 45.
    Asnake, Solomon
    et al.
    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.
    Species differences in ligand interaction and activation of estrogen receptors in fish and human2019In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 195, article id 105450Article in journal (Refereed)
    Abstract [en]

    Estrogen receptor (ER) sequences vary between species and this suggests that there are differences in the ligand-specificity, leading to species-specific effects. This would indicate that it is not possible to generalize effects across species. In this study, we investigated the differences in activation potencies and binding affinities of ER´s alpha (α) and beta (β) in human, zebrafish and sea bream to elucidate species differences in response to estradiol, estrone, estriol and methyltestosterone. In vitro analysis showed that estradiol had the highest activity for all the ER´s except for human ERβ and seabream ERβ2. Alignment of the ligand binding domain and ligand binding pocket (LBP) residues of the three species showed that different residues were involved in the LBPs which led to differences in pocket volume, affected binding affinity and orientation of the ligands. By combining in silico and in vitro results, it was possible to identify the ligand specificities of ER´s. The results demonstrated that the human ER´s show lower resolution in ligand-dependent activation, suggesting higher promiscuity, than the zebrafish and seabream ER´s. These results show species-specificity of ER´s and suggest that species-specific differences must be taken into consideration when studying different exposure scenarios.

  • 46.
    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, p. 1993-2000Article 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.

  • 47.
    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)
  • 48.
    Atterby, Clara
    et al.
    Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden .
    Börjesson, Stefan
    Department of Animal Health and Antimicrobial strategies, National Veterinary Institute (SVA), Uppsala, Sweden .
    Ny, Sofia
    Public Health Agency of Sweden, Stockholm, Sweden, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden .
    Järhult, Josef D
    Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Section of Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden .
    Byfors, Sara
    Public Health Agency of Sweden, Stockholm, Sweden .
    Bonnedahl, Jonas
    Center for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden; Department of Infectious Diseases, Kalmar County Council, Kalmar, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden .
    ESBL-producing Escherichia coli in Swedish gulls: A case of environmental pollution from humans?2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 12, article id e0190380Article in journal (Refereed)
    Abstract [en]

    ESBL-producing bacteria are present in wildlife and the environment might serve as a resistance reservoir. Wild gulls have been described as frequent carriers of ESBL-producing E. coli strains with genotypic characteristics similar to strains found in humans. Therefore, potential dissemination of antibiotic resistance genes and bacteria between the human population and wildlife need to be further investigated. Occurrence and characterization of ESBL-producing E. coli in Swedish wild gulls were assessed and compared to isolates from humans, livestock and surface water collected in the same country and similar time-period. Occurrence of ESBL-producing E. coli in Swedish gulls is about three times higher in gulls compared to Swedish community carriers (17% versus 5%) and the genetic characteristics of the ESBL-producing E. coli population in Swedish wild gulls and Swedish human are similar. ESBL-plasmids IncF- and IncI1-type carrying ESBL-genes blaCTX-M-15 or blaCTX-M-14 were most common in isolates from both gulls and humans, but there was limited evidence of clonal transmission. Isolates from Swedish surface water harbored similar genetic characteristics, which highlights surface waters as potential dissemination routes between wildlife and the human population. Even in a low-prevalence country such as Sweden, the occurrence of ESBL producing E. coli in wild gulls and the human population appears to be connected and the occurrence of ESBL-producing E. coli in Swedish gulls is likely a case of environmental pollution.

  • 49.
    Atterby, Clara
    et al.
    Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Osbjer, Kristina
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden; Food and Agriculture Organization of the United Nations, Phnom Penh, Cambodia.
    Tepper, Viktoria
    Institute of Environmental Engineering, ETH Zürich, Switzerland.
    Rajala, Elisabeth
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
    Hernandez, Jorge
    Center for Ecology and Evolution in Microbial Model Systems Linnaeus University, Kalmar, Sweden; Department of Infectious Diseases, Kalmar County Council, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Diagnostic Centrum, Clinic Microbiologic Laboratory, Kalmar County Hospital, Kalmar, Sweden.
    Seng, Sokerya
    Food and Agriculture Organization of the United Nations, Phnom Penh, Cambodia.
    Holl, Davun
    General Directorate of Animal Health and Production, Ministry of Agriculture, Forestry and Fisheries, Phnom Penh, Cambodia.
    Bonnedahl, Jonas
    Center for Ecology and Evolution in Microbial Model Systems Linnaeus University, Kalmar, Sweden; Department of Infectious Diseases, Kalmar County Council, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Börjesson, Stefan
    Department of Animal Health and Antimicrobial strategies, National Veterinary Institute (SVA), Uppsala, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Magnusson, Ulf
    Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
    Järhult, Josef D
    Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Carriage of carbapenemase- and extended-spectrum cephalosporinase-producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia; gender and age differences and detection of blaOXA-48 in humans.2019In: Zoonoses and Public Health, ISSN 1863-1959, E-ISSN 1863-2378, Vol. 66, no 6, p. 603-617Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study investigates the frequency and characteristics of carbapenemase-producing Escherichia coli/Klebsiella pneumoniae (CPE/K) and extended-spectrum cephalosporinase-producing E. coli/K. pneumoniae (ESCE/K) in healthy humans and livestock in rural Cambodia. Additionally, household practices as risk factors for faecal carriage of ESCE/K are identified.

    METHODS: Faecal samples were obtained from 307 humans and 285 livestock including large ruminants, pigs and poultry living in 100 households in rural Cambodia in 2011. Each household was interviewed, and multilevel logistic model determined associations between household practices/meat consumption and faecal carriage of ESCE/K. CPE and ESCE/K were detected and further screened for colistin resistance genes.

    RESULTS: CPE/K isolates harbouring blaOXA-48 were identified in two humans. The community carriage of ESCE/K was 20% in humans and 23% in livestock. The same ESBL genes: blaCTX-M-15 , blaCTX-M-14 , blaCTX-M-27 , blaCTX-M-55 , blaSHV-2 , blaSHV-12 , blaSHV-28 ; AmpC genes: blaCMY-2 , blaCMY-42, blaDHA-1 ; and colistin resistance genes: mcr-1-like and mcr-3-like were detected in humans and livestock. ESCE/K was frequently detected in women, young children, pigs and poultry, which are groups in close contact. The practice of burning or burying meat waste and not collecting animal manure indoors and outdoors daily were identified as risk factors for faecal carriage of ESCE/K.

    CONCLUSIONS: Faecal carriage of E. coli and K. pneumoniae harbouring extended-spectrum cephalosporinase genes are common in the Cambodian community, especially in women and young children. Exposure to animal manure and slaughter products are risk factors for intestinal colonization of ESCE/K in humans.

  • 50.
    Atterby, Clara
    et al.
    Section of Clinical Microbiology and Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
    Ramey, Andrew M
    US Geological Survey, Alaska Science Center, Anchorage, AK, USA.
    Hall, Gabriel Gustafsson
    Section of Clinical Microbiology and Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Järhult, Josef
    Section of Clinical Microbiology and Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
    Börjesson, Stefan
    Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
    Bonnedahl, Jonas
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden;Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Increased prevalence of antibiotic-resistant E. coli in gulls sampled in Southcentral Alaska is associated with urban environments2016In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, no 1, article id 32334Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Antibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls (Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats.

    METHODS: Escherichia coli was cultured (n=115 isolates) from fecal samples of gulls (n=160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula.

    RESULTS: Screening of E. coli from fecal samples collected from glaucous-winged gulls (Larus glaucescens) at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [Larus argentatus], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected.

    CONCLUSION: Our findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health.

1234567 1 - 50 of 1175
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf