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  • 1.
    Abbas, Monika
    Örebro University, School of Health and Medical Sciences.
    Bedömning av variabler vid postocklusiv reaktiv hyperemi (PORH)-test med Laser Doppler Flowmetry teknik2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 2.
    Abdallah Athumani, Ngenya
    Örebro University, School of Health Sciences.
    Characterization of tick-born encephalitis and West Nile virus non-structural 5 protein interactions with host factors involved in immune evasion and cellular apoptosis.2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 3.
    Akhras, Michael S.
    et al.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Pettersson, Erik
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Diamond, Lisa
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Unemo, Magnus
    Örebro University Hospital.
    Okamoto, Jennifer
    Dept Bioengn, Stanford Univ, Stanford CA, USA.; Howard Hughes Med Inst, Stanford Univ, Stanford CA, USA.
    Davis, Ronald W.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA , USA.
    Pourmand, Nader
    Dept Biomol Engn, University of California, Santa Cruz CA, USA.
    The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id UNSP e76696Article in journal (Refereed)
    Abstract [en]

    Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e. g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing.

  • 4.
    Akil, Shahnaz
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Discrimination of abnormal ST-deviation patterns from those caused by acute coronary occlusion, using 12-lead electrocardiogram-based computed elctrocardiograpich imaging2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 5.
    Al Hwamdeh, Yaseen
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Urinary Stone Diagnosis Non: Contrast Computed Tomography versus Intravenous Urography2015Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
  • 6.
    Altun, O.
    et al.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Örebro University, Örebro, Sweden.
    Almuhayawi, M.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia.
    Strålin, K.
    Department of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Özenci, V.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Rapid identification of Streptococcus pneumoniae in blood cultures by using the ImmuLex, Slidex and Wellcogen latex agglutination tests and the BinaxNOW antigen test2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 4, p. 579-585Article in journal (Refereed)
    Abstract [en]

    Rapid identification of Streptococcus pneumoniae in blood culture (BC) bottles is important for early directed antimicrobial therapy in pneumococcal bacteraemia. We evaluated a new latex agglutination (LA) test on BC bottles, the ImmuLex™ S. pneumoniae Omni (Statens Serum Institut, Denmark), and compared the performance with the Slidex® pneumo-Kit (bioMérieux, France) and the Wellcogen™ S. pneumoniae (Remel, UK) LA tests, as well as the BinaxNOW® S. pneumoniae (Alere, USA) antigen test. The four tests were directly applied on 358 positive BC bottles with Gram-positive cocci in pairs or chains and on 15 negative bottles. Valid test results were recorded in all cases for ImmuLex and BinaxNOW and in 88.5 % (330/373) and 94.1 % (351/373) of cases for Slidex and Wellcogen, respectively. Based on bottles positive for S. pneumoniae by conventional methods, the sensitivity of ImmuLex was 99.6 %, similar to the other tests (range, 99.6-100 %). Based on bottles positive for non-pneumococcal pathogens, the specificity of ImmuLex was 82.6 %, in comparison to 97.6 % for Slidex (p < 0.01) and 85.4 % for Wellcogen (p = ns). The BinaxNOW test had a lower specificity (64.1 %) than any LA test (p < 0.01). On BC bottles positive for α-haemolytic streptococci, ImmuLex was positive in 12/67 (17.9 %) cases, Slidex in 2/59 (3.4 %) cases, Wellcogen in 11/64 (17.2 %) cases and BinaxNOW in 25/67 (37.3 %) cases. In conclusion, the ImmuLex test provides a valid and sensitive technique for the rapid detection of S. pneumoniae in BC bottles, similar to the other compared methods. However, the specificity was sub-optimal, since the test may cross-react with other Gram-positive bacteria.

  • 7.
    Ambaye, Sisay
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Method development and improvement of Human papillomavirus (HPV) detection and genotyping2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 8.
    Andersson, Anna-Maria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Interaction between the periodontal pathogen Porphyromonas gingivalis and human fibroblasts - effects on cell viability and cytokine production2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The oral bacterium Porphyromonas gingivalis is one of the key-pathogens causing the inflammatory disease periodontitis, as well as being associated with the progression of atherosclerosis. The bacterium has different virulence factors that induce an inflammation, including production of cytokines and chemokines, which has a role in both diseases. The proteases, called gingipains, are one important group of virulence factors that for example degrade host proteins, causing tissue damage. The aim of this study is to investigate whether viable P. gingivalis affects fibroblasts’ viability and modulate the associated immuno-regulatory mechanisms. The fibroblasts were therefore stimulated with the bacteria and the viability and interleukin (IL)-8 production were measured. The morphology was also studied using microscopy. We found that P. gingivalis adheres to fibroblasts, which survives and proliferate even at high concentrations of bacteria over time. In addition viable bacteria induce a production of IL-8, however the chemokine is probably degraded by the gingipains at high concentrations of bacteria. In conclusion, P. gingivalis adheres to fibroblasts, stimulate fibroblast proliferation, and trigger the release of IL-8, which is then decreased, possibly due to the catalytic activity of the gingipains.  

  • 9.
    Andersson, Carina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Utvärdering av Hepatit C Virus RNA Test med automatiserad provberedning2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 10.
    Andersson, Christoffer R.
    et al.
    Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Bergquist, Jonas
    Department of Chemistry (BMC), Analytical Chemistry and Neurochemistry, Uppsala University, Uppsala, Sweden.
    Theodorsson, Elvar
    Departments of Clinical Chemistry and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Comparisons between commercial salivary testosterone enzyme-linked immunosorbent assay kits2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 8, p. 582-586Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined.

    AIM OF STUDY: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec).

    METHODS: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits.

    RESULTS: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values > .77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained.

    CONCLUSIONS: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons.

  • 11.
    Andersson, Elin
    Örebro University, School of Health Sciences.
    PREANALYTISK HÅLLBARHETSSTUDIE: IN VITRO BILDNING AV FOSFATIDYLETANOL IBLODET2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 12.
    Andersson, Linda
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Simultaneous detection of multiple Betalactamases with MALDI-TOF2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 13.
    Andonova, Teodora
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Effect of Omega-3 on Cholesterol Homeostasis in Mouse Brain2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 14.
    Antila, Kari
    et al.
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Lötjönen, Jyrki
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Thurfjell, Lennart
    GE Healthcare, Stockholm, Sweden.
    Laine, Jarmo
    Nexstim Ltd, Helsinki, Finland.
    Massimini, Marcello
    University of Milan, Milan, Italy.
    Rueckert, Daniel
    Imperial College London, London, United Kingdom.
    Zubarev, Roman A.
    Karolinska Institutet, Stockholm, Sweden.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Tampere, Finland.
    van Gils, Mark
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Mattila, Jussi
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Hviid Simonsen, Anja
    Rigshospitalet, Copenhagen, Denmark.
    Waldemar, Gunhild
    Rigshospitalet, Copenhagen, Denmark.
    Soininen, Hilkka
    University of Eastern Finland, Kuopio, Finland.
    The PredictAD project: development of novel biomarkers and analysis software for early diagnosis of the Alzheimer's disease2013In: Interface Focus, ISSN 2042-8898, E-ISSN 2042-8901, Vol. 3, no 2, article id 20120072Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is the most common cause of dementia affecting 36 million people worldwide. As the demographic transition in the developed countries progresses towards older population, the worsening ratio of workers per retirees and the growing number of patients with age-related illnesses such as AD will challenge the current healthcare systems and national economies. For these reasons AD has been identified as a health priority, and various methods for diagnosis and many candidates for therapies are under intense research. Even though there is currently no cure for AD, its effects can be managed. Today the significance of early and precise diagnosis of AD is emphasized in order to minimize its irreversible effects on the nervous system. When new drugs and therapies enter the market it is also vital to effectively identify the right candidates to benefit from these. The main objective of the PredictAD project was to find and integrate efficient biomarkers from heterogeneous patient data to make early diagnosis and to monitor the progress of AD in a more efficient, reliable and objective manner. The project focused on discovering biomarkers from biomolecular data, electrophysiological measurements of the brain and structural, functional and molecular brain images. We also designed and built a statistical model and a framework for exploiting these biomarkers with other available patient history and background data. We were able to discover several potential novel biomarker candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials.

  • 15.
    Arinell, Karin
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Acute Internal Medicine, Centralsjukhuset, Karlstad, Sweden.
    Blanc, Stéphane
    CNRS UMR 7178, Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, Strasbourg, France.
    Welinder, Karen Gjesing
    Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    Støen, Ole Gunnar
    Norwegian Institute for Nature Research, Trondheim, Norway.
    Evans, Alina L.
    Department of Forestry and Wildlife Management, Inland Norway University of Applied Sciences, Koppang, Norway.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Physical inactivity and platelet function in humans and brown bears: A comparative study2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, no 1, p. 87-90Article in journal (Refereed)
    Abstract [en]

    Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few.

    Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

  • 16.
    Aronsson, Ulrika
    Örebro University, School of Health Sciences.
    Metodutvärdering och mervärde av Treponema pallidum IgM analys vid diagnostik av syfilis2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 17.
    Asaei, Ava
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Effekten av interleukin-6, interleukin-17 och kombinationen av dessa på inflammatoriskt svar i humana endotelceller2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 18.
    Assadi, Ghazaleh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden .
    Vesterlund, Liselotte
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Mazzurana, Luca
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Cordeddu, Lina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Schepis, Danika
    Rheumatology unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Mjösberg, Jenny
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden .
    Ruhrmann, Sabrina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fabbri, Alessia
    Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy .
    Vukojevic, Vladana
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Percipalle, Piergiorgio
    Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Salomons, Florian A.
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Laurencikiene, Jurga
    Lipid laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Törkvist, Leif
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden .
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain .
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168276Article in journal (Refereed)
    Abstract [en]

    Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.

    Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.

    Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.

    Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 19.
    Awadalla, Mohamed
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Homology Models of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1: Molecular Dynamics Refinement and Evaluation of Statins Docking2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 20.
    Awdalla, Mohamed
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Homology Models of Human Retinoic Acid Hydroxylase CYP26A1 and CYP26B1: Molecular Dynamics Refinement and Evaluation of Statins Docking2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 21.
    Azrakhshi, Shler
    Örebro University, School of Health Sciences.
    Jämförelse mellan ACUSON SC2000 och General Electric Vivid E9 med pulsad vävnadsdoppler2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 22.
    Barqasho, Babilonia
    et al.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Nowak, Piotr
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden; Division of Infectious Diseases, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Abdurahman, Samir
    Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden .
    Walther-Jallow, Lillian
    Center for Infectious Medicine, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Sönnerborg, Anders
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden; Division of Infectious Diseases, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Implications of the release of high-mobility group box 1 protein from dying cells during human immunodeficiency virus type 1 infection in vitro2010In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 91, no Pt 7, p. 1800-1809Article in journal (Refereed)
    Abstract [en]

    Plasma levels of high-mobility group box 1 protein (HMGB1) are elevated during the course of human immunodeficiency virus type 1 (HIV-1) infection and the molecule has an impact on virus replication. This study investigated the mode of cell death and release of HMGB1 during HIV-1 infection in vitro. MT4 cells and primary CD4(+) T cells were infected with HIV-1 isolates, and HMGB1 release was monitored in relation to cytopathic effects (CPE) and apoptosis. HMGB1 release from cells was analysed by Western blotting. For MT4 cells, an enzyme-linked immunosorbent spot (ELISPOT) assay was adapted to measure the release during necrosis. Lactate dehydrogenase (LDH) activity was quantified using a commercial assay. Flow cytometry was used to determine the level of infection and apoptosis. MT4 cells were > or =90 % infected at 48 h post-infection (p.i.). CPE was first observed at 60 h and correlated with release of HMGB1, LDH activity and caspase-3 (C3) activation. HMGB1 spots were clearly detected by ELISPOT assay at 72 h p.i. Annexin V and C3 staining showed that apoptosis was substantially involved in HIV-1-related cell death. Addition of Z-VAD (a caspase inhibitor) in a single dose at 24 or 40 h p.i. decreased both the number of caspase-positive cells and the release of HMGB1. Infection of primary CD4(+) T cells showed a 22 % (median) infection rate at 96 h. Related CPE corresponded to LDH and HMGB1 release. Both necrosis and apoptosis contributed to HMGB1 liberation during HIV-1-induced cell death and the protein could induce tumour necrosis factor-alpha release from peripheral mononuclear blood cells. These data imply that passive HMGB1 release contributes to the excessive immune activation characteristic of HIV-1 pathogenesis.

  • 23.
    Basic, Vladimir
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Molecular mechanisms mediating development of pulmonary cachexia in COPD2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cigarette smoking (CS) represents the main causative agent underlying development and progress of COPD. Recently, involvement of CS in the pathogenesis of COPDassociated muscle abnormalities is becoming increasingly evident. Nevertheless, involved triggers and underlying mechanisms remain largely unknown. This study was conceived in order to examine effects of cigarette smoke exposure on skeletal muscle morphology, vascular supply and function. For this purpose, we have specifically designed murine COPD/emphysema model and gastrocnemius muscle was examined, while in vitro experiments were conducted using murine C2C12 skeletal muscle myocytes.

    In addition to the mild emphysematous changes present in the lungs of CS-exposed mice, our results demonstrated evident signs of muscle atrophy reflected by decreased fiber cross-sectional area, profound fiber size variation and reduced body mass. Furthermore, we have observed impairment in terminal myogenesis and lower number of myonuclei in skeletal muscles of CS-exposed animals despite evident activation of muscle repair process. Additionally, our results demonstrate capillary rarefaction in skeletal muscles of CS-exposed animals which was associated with deregulation of hypoxia-angiogenesis signaling, reduced levels of angiogenic factors such as HIF1-α and VEGF and enhanced expression of VHL and its partner proteins PHD2 and Ube2D1. The results of our in-vitro experiments demonstrated that VHL and its ubiquitination machinery can be synergistically regulated by TNF and hypoxia consequentially impairing angiogenic potential of skeletal muscle myocytes. Finally, we have shown that CS elicits chronic ER stress in murine skeletal muscles which is associated with activation of ERAD and apoptotic pathways as mirrored by elevated expression of Usp19, caspase 12 and caspase 3 in skeletal muscles of CSexposed animals. Moreover, molecular and morphological alterations in CS-exposed mice resulted in impairment of muscle function as reflected by their impaired exercise capacity.

    Taken together, from our results it is evident that cigarette smoke exposure elicits set of morphological, vascular and functional changes highly resembling those observed in COPD. Additionally, CS induces wide range of molecular alterations and signaling pathway deregulations suggesting profound effects of cigarette smoke exposure on skeletal muscle cell homeostasis.

    List of papers
    1. Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle
    Open this publication in new window or tab >>Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle
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    2012 (English)In: American Journal of Physiology - Lung cellular and Molecular Physiology, ISSN 1040-0605, E-ISSN 1522-1504, Vol. 303, no 6, p. L519-L527Article in journal (Refereed) Published
    Abstract [en]

    Cigarette smoke (CS) is a well established risk factor in the development of chronic obstructive pulmonary disease (COPD). In contrast, the extent to which CS exposure contributes to the development of the systemic manifestations of COPD, such as skeletal muscle dysfunction and wasting remains largely unknown. Decreased skeletal muscle capillarization has been previously reported in early stages of COPD and might play an important role in the development of COPD-associated skeletal muscle abnormalities. To investigate the effects of chronic CS exposure on skeletal muscle capillarization and exercise tolerance a mouse model of CS exposure was used. The129/SvJ mice were exposed to CS for 6 months, and the expression of putative elements of the hypoxia-angiogenic signaling cascade as well as muscle capillarization were studied. Additionally, functional tests assessing exercise tolerance/endurance were performed in mice. Compared to controls, skeletal muscles from CS-exposed mice exhibited significantly enhanced expression of von Hippel-Lindau tumor suppressor (VHL), ubiquitin-conjugating enzyme E2D1 (UBE2D1) and prolyl hydroxylase-2 (PHD2). In contrast, hypoxia-inducible factor-1 (HIF1-α) and vascular endothelial growth factor (VEGF) expression was reduced. Furthermore, reduced muscle fiber cross-sectional area, decreased skeletal muscle capillarization, and reduced exercise tolerance were also observed in CS-exposed animals. Taken together, the current results provide evidence linking chronic CS exposure and induction of VHL expression in skeletal muscles leading towards impaired hypoxia-angiogenesis signal transduction, reduced muscle fiber cross-sectional area and decreased exercise tolerance.

    Place, publisher, year, edition, pages
    Bethesda, USA: American Physiological Society, 2012
    Keywords
    Capillaries, chronic obstructive pulmonary disease, hypoxia inducible factor-1 alpha, pulmonary cachexia syndrome, vascular endothelial growth factor
    National Category
    Medical and Health Sciences Physiotherapy
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-24177 (URN)10.1152/ajplung.00007.2012 (DOI)000309109300005 ()22842216 (PubMedID)2-s2.0-84866418091 (Scopus ID)
    Funder
    NIH (National Institute of Health)
    Note

    Funding Agencies:

    Olle Engkvist Byggmastare Fund, Sweden

    NIEHS Environmental Health Science Center grant 

    Available from: 2012-07-31 Created: 2012-07-31 Last updated: 2018-05-09Bibliographically approved
    2. Chronic cigarette smoke exposureimpairs skeletal muscle regenerative capacity in murineCOPD/emphysema model.
    Open this publication in new window or tab >>Chronic cigarette smoke exposureimpairs skeletal muscle regenerative capacity in murineCOPD/emphysema model.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Cigarette smoke (CS) is a well established risk factor in the development of COPD and irreversible airflow limitation. In contrast, the extent to which CS exposure contributes to development of peripheral skeletal muscle dysfunction and wasting remains largely unknown. Decline in skeletal muscle regenerative capacity has been previously reported in COPD patients.

    Methods: To investigate effects of chronic CS exposure on skeletal muscle regenerative capacity, 129/SvJ mice were exposed to CS for 6 months. The expression levels of myogenin, Jarid2, Znf496, Notch1, Pax7, Fgf1 and Myh3, which are known to regulate skeletal muscle myogenesis, were studied. Additionally, number of fibers with central nuclei, myonuclei number and mean fiber cross-sectional area were assessed.

    Results: Compared to controls, skeletal muscles from CS-exposed mice exhibited significantly decreased expression of Jarid2, coupled with enhanced expression of Znf496, Notch1, Pax7, Fgf1 and Myh3. Expression of myogenin, a marker of terminally differentiated myofibers, was reduced. Furthermore, reduced muscle fiber crosssectional area, increased number of fibers with central nuclei and reduced myonuclei number were also observed in CS-exposed animals.

    Conclusions: Taken together, current results provide evidence linking chronic CS exposure and an ongoing damage/repair process as well as impaired regenerative capacity in skeletal muscles of CS-exposed mice.

    Keywords
    cigarette smoke, chronic obstructive pulmonary disease, skeletal muscle dysfunction, skeletal muscle regeneration
    National Category
    Otorhinolaryngology
    Research subject
    Oto-Rhino-Laryngology
    Identifiers
    urn:nbn:se:oru:diva-38189 (URN)
    Note

    Funding and support:

    Olle Engkvist Byggmästare Fund,

    Åke WibergFoundation, Sweden

    and the research funds of the Department of Medicine,Danderyd Hospital, Stockholm(to S.M.A-H),

    Örebro university grant to doctoralsstudents (We thank the Developmental Studies Hybridoma Bank (DSHB, Universityof Iowa, IA, USA)) for antibody against Pax7

    Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-10-17Bibliographically approved
    3. TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes
    Open this publication in new window or tab >>TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes
    2014 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 34, no 1, p. 228-236Article in journal (Refereed) Published
    Abstract [en]

    Decreased skeletal muscle capillarization is considered to significantly contribute to the development of pulmonary cachexia syndrome (PCS) and progressive muscle wasting in several chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). It is unclear to which extent the concurrent presence of systemic inflammation contributes to decreased skeletal muscle capillarization under these conditions. The present study was designed to examine in vitro the effects of the pro-inflammatory cytokine, tumor necrosis factor (TNF), on the regulation of hypoxia-angiogenesis signal transduction and capillarization in skeletal muscles. For this purpose, fully differentiated C2C12 skeletal muscle myocytes were stimulated with TNF and maintained under normoxic or hypoxic conditions. The expression levels of the putative elements of the hypoxia-angiogenesis signaling cascade were examined using qPCR, western blot analysis and immunofluorescence. Under normoxic conditinos, TNF stimulation increased the protein expression of anti-angiogenic von-Hippel Lindau (VHL), prolyl hydroxylase (PHD)2 and ubiquitin conjugating enzyme 2D1 (Ube2D1), as well as the total ubiquitin content in the skeletal muscle myocytes. By contrast, the expression levels of hypoxia-inducible factor 1‑α (HIF1-α) and those of its transcriptional targets, vascular endothelial growth factor (VEGF)A and glucose transporter 1 (Glut1), were markedly reduced. In addition, hypoxia increased the expression of the VHL transcript and further elevated the VHL protein expression levels in C2C12 myocytes following TNF stimulation. Consequently, an impaired angiogenic potential was observed in the TNF-stimulated myocytes during hypoxia. In conclusion, TNF increases VHL expression and disturbs hypoxia-angiogenesis signal transduction in skeletal muscle myocytes. The current findings provide a mechanism linking systemic inflammation and impaired angiogenesis in skeletal muscle. This is particularly relevant to further understanding the mechanisms mediating muscle wasting and cachexia in patients with chronic inflammatory diseases, such as COPD.

    Place, publisher, year, edition, pages
    Spandidos Publications, 2014
    National Category
    Medical Biotechnology
    Research subject
    Medical Disability Research
    Identifiers
    urn:nbn:se:oru:diva-35141 (URN)10.3892/ijmm.2014.1776 (DOI)000338178000027 ()24820910 (PubMedID)2-s2.0-84902649801 (Scopus ID)
    Available from: 2014-05-25 Created: 2014-05-25 Last updated: 2018-06-07Bibliographically approved
    4. Cigarette smoke exposure up-regulates Ubiquitin specific protease 19 in murine skeletal muscles as an adaptive response to prolonged ER stress
    Open this publication in new window or tab >>Cigarette smoke exposure up-regulates Ubiquitin specific protease 19 in murine skeletal muscles as an adaptive response to prolonged ER stress
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Enhanced protein degradation via ubiquitin proteolytic system (UPS) was demonstrated to play an important role in the pathogenesis of cachexia syndrome and muscle wasting in patients with COPD and animal models of the disease. The role of cigarette smoke (CS) exposure in eliciting these abnormalities remains largely unknown. Usp19 is a member of UPS suggested to be involved in progressive muscle wasting in different catabolic conditions. However, factors regulating Usp19 expression, activity and correlation/s with CS-induced muscle atrophy remainunclear.

    Methods: To address these questions, 129 SvJ mice were exposed to cigarette smoke for 6 months and the gastrocnemius muscles were collected. Expression levels of Usp19 as well as pivotal mediators of ER stress response have been studied using PCR, qPCR, western blot and immunofluorescence. Factors regulating muscle Usp19 expression were studied using in-silico analysis of Usp19 promoter as well as by stimulating C2C12 myocytes with different inducers of ER stress including hypoxia, TNF and tunicamycin. Finally, Usp19 expression was depleted in C2C12 myocytes using specific Usp19 siRNA quadriplex and the expression of pivotal myogenic regulators were analyzed.

    Results: Usp19 mRNA expression was enhanced in skeletal muscles of CS-exposed mice. Concurrently, ER stress-associated Caspase 12 and Caspase 3 were activated in the CS-exposed group. Analysis of Usp19 promoter sequence revealed binding sites for ER stress response transcription factors such as HSF, STRE1 and AML1-α. Exposure of C2C12 myocytes to tunicamycin but not hypoxia elevated expression levels of Usp19. TNFstimulation elevated Usp19 protein expression but inhibited its RNA transcription in a dose- and time-dependent manner. Finally, Usp19 overexpression in tunicamycin-treated myocytes was accompanied by reduced expression of myosin heavy chain and tropomyosin and their levels were increased after knocking down Usp19 in C2C12 myocytes.

    Conclusions: In summary, our data demonstrated elevated expression of Usp19 in skeletal muscles of CS-exposed 129 SvJ mice. Moreover, Usp19 overexpression was associated with muscle adaptations to ER stress and suppression of myogenesis. Taken together; our results might provide further insight into molecular mechanisms underlying development and progression of skeletal muscle abnormalities in response to chronic cigarette smoke exposure.

    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-38194 (URN)
    Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-10-17Bibliographically approved
    5. The periodontal pathogen Porphyromonas gingivalis changes the gene expression in vascular smooth muscle cells involving the TGFbeta/Notch signalling pathway and increased cell proliferation
    Open this publication in new window or tab >>The periodontal pathogen Porphyromonas gingivalis changes the gene expression in vascular smooth muscle cells involving the TGFbeta/Notch signalling pathway and increased cell proliferation
    Show others...
    2013 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 14, p. 770-Article in journal (Refereed) Published
    Abstract [en]

    Background: Porphyromonas gingivalis is a gram-negative bacterium that causes destructive chronic periodontitis. In addition, this bacterium is also involved in the development of cardiovascular disease. The aim of this study was to investigate the effects of P. gingivalis infection on gene and protein expression in human aortic smooth muscle cells (AoSMCs) and its relation to cellular function.

    Results: AoSMCs were exposed to viable P. gingivalis for 24 h, whereafter confocal fluorescence microscopy was used to study P. gingivalis invasion of AoSMCs. AoSMCs proliferation was evaluated by neutral red assay. Human genome microarray, western blot and ELISA were used to investigate how P. gingivalis changes the gene and protein expression of AoSMCs. We found that viable P. gingivalis invades AoSMCs, disrupts stress fiber structures and significantly increases cell proliferation. Microarray results showed that, a total of 982 genes were identified as differentially expressed with the threshold log2 fold change >|1| (adjust p-value <0.05). Using bioinformatic data mining, we demonstrated that up-regulated genes are enriched in gene ontology function of positive control of cell proliferation and down-regulated genes are enriched in the function of negative control of cell proliferation. The results from pathway analysis revealed that all the genes belonging to these two categories induced by P. gingivalis were enriched in 25 pathways, including genes of Notch and TGF-beta pathways.

    Conclusions: This study demonstrates that P. gingivalis is able to invade AoSMCs and stimulate their proliferation. The activation of TGF-beta and Notch signaling pathways may be involved in the bacteria-mediated proliferation of AoSMCs. These findings further support the association between periodontitis and cardiovascular diseases.

    Keywords
    Porphyromonas gingivalis, Aortic smooth muscle cells, Proliferation, Gene expression profiling
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:oru:diva-33287 (URN)10.1186/1471-2164-14-770 (DOI)000328639800002 ()24209892 (PubMedID)2-s2.0-84887327838 (Scopus ID)
    Funder
    Swedish Research Council, 2008-2459Swedish Heart Lung Foundation, 2011-0632
    Note

    Funding Agency: Foundation of Olle Engkvist; Foundation of Mats Kleberg (se även Forskningsfinansiär)

    Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2018-01-11Bibliographically approved
  • 24.
    Basic, Vladimir T.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jacobsen, Annette
    Charles Sturt University, Sydney NSW, Australien.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Abdel-Halim, Samy
    Danderyd Hospital, Stockholm, Sweden.
    TNF stimulation induces VHL overexpression and impairs angiogenic potential in skeletal muscle myocytes2014In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 34, no 1, p. 228-236Article in journal (Refereed)
    Abstract [en]

    Decreased skeletal muscle capillarization is considered to significantly contribute to the development of pulmonary cachexia syndrome (PCS) and progressive muscle wasting in several chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). It is unclear to which extent the concurrent presence of systemic inflammation contributes to decreased skeletal muscle capillarization under these conditions. The present study was designed to examine in vitro the effects of the pro-inflammatory cytokine, tumor necrosis factor (TNF), on the regulation of hypoxia-angiogenesis signal transduction and capillarization in skeletal muscles. For this purpose, fully differentiated C2C12 skeletal muscle myocytes were stimulated with TNF and maintained under normoxic or hypoxic conditions. The expression levels of the putative elements of the hypoxia-angiogenesis signaling cascade were examined using qPCR, western blot analysis and immunofluorescence. Under normoxic conditinos, TNF stimulation increased the protein expression of anti-angiogenic von-Hippel Lindau (VHL), prolyl hydroxylase (PHD)2 and ubiquitin conjugating enzyme 2D1 (Ube2D1), as well as the total ubiquitin content in the skeletal muscle myocytes. By contrast, the expression levels of hypoxia-inducible factor 1‑α (HIF1-α) and those of its transcriptional targets, vascular endothelial growth factor (VEGF)A and glucose transporter 1 (Glut1), were markedly reduced. In addition, hypoxia increased the expression of the VHL transcript and further elevated the VHL protein expression levels in C2C12 myocytes following TNF stimulation. Consequently, an impaired angiogenic potential was observed in the TNF-stimulated myocytes during hypoxia. In conclusion, TNF increases VHL expression and disturbs hypoxia-angiogenesis signal transduction in skeletal muscle myocytes. The current findings provide a mechanism linking systemic inflammation and impaired angiogenesis in skeletal muscle. This is particularly relevant to further understanding the mechanisms mediating muscle wasting and cachexia in patients with chronic inflammatory diseases, such as COPD.

  • 25.
    Basic, Vladimir T.
    et al.
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Jacobsen, Annette
    Department of Clinical Medicine, Örebro University, Örebro, Sweden; School of Biomedical Sciences, Charles Sturt University, WaggaWagga, Australia.
    Tadele, Elsa
    Department of Clinical Medicine, Örebro University, Örebro, Sweden; Medical University of Giessen, Molecular Biology and Medicine of the Lung program, Giessen, Germany.
    Banjop- Kharlyngdoh, Joubert
    Örebro University, School of Science and Technology.
    Sirsjö, Allan
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Abdel-Halim, Samy M.
    Division of Respiratory Medicine and Allergology, Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Cigarette smoke exposure up-regulates Ubiquitin specific protease 19 in murine skeletal muscles as an adaptive response to prolonged ER stressManuscript (preprint) (Other academic)
    Abstract [en]

    Enhanced protein degradation via ubiquitin proteolytic system (UPS) was demonstrated to play an important role in the pathogenesis of cachexia syndrome and muscle wasting in patients with COPD and animal models of the disease. The role of cigarette smoke (CS) exposure in eliciting these abnormalities remains largely unknown. Usp19 is a member of UPS suggested to be involved in progressive muscle wasting in different catabolic conditions. However, factors regulating Usp19 expression, activity and correlation/s with CS-induced muscle atrophy remainunclear.

    Methods: To address these questions, 129 SvJ mice were exposed to cigarette smoke for 6 months and the gastrocnemius muscles were collected. Expression levels of Usp19 as well as pivotal mediators of ER stress response have been studied using PCR, qPCR, western blot and immunofluorescence. Factors regulating muscle Usp19 expression were studied using in-silico analysis of Usp19 promoter as well as by stimulating C2C12 myocytes with different inducers of ER stress including hypoxia, TNF and tunicamycin. Finally, Usp19 expression was depleted in C2C12 myocytes using specific Usp19 siRNA quadriplex and the expression of pivotal myogenic regulators were analyzed.

    Results: Usp19 mRNA expression was enhanced in skeletal muscles of CS-exposed mice. Concurrently, ER stress-associated Caspase 12 and Caspase 3 were activated in the CS-exposed group. Analysis of Usp19 promoter sequence revealed binding sites for ER stress response transcription factors such as HSF, STRE1 and AML1-α. Exposure of C2C12 myocytes to tunicamycin but not hypoxia elevated expression levels of Usp19. TNFstimulation elevated Usp19 protein expression but inhibited its RNA transcription in a dose- and time-dependent manner. Finally, Usp19 overexpression in tunicamycin-treated myocytes was accompanied by reduced expression of myosin heavy chain and tropomyosin and their levels were increased after knocking down Usp19 in C2C12 myocytes.

    Conclusions: In summary, our data demonstrated elevated expression of Usp19 in skeletal muscles of CS-exposed 129 SvJ mice. Moreover, Usp19 overexpression was associated with muscle adaptations to ER stress and suppression of myogenesis. Taken together; our results might provide further insight into molecular mechanisms underlying development and progression of skeletal muscle abnormalities in response to chronic cigarette smoke exposure.

  • 26.
    Berndtson, E.
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Emanuelson, U.
    Swedish Association for Livestock Breeding and Production, Eskilstuna, Sweden .
    Engvall, A.
    Department of Epizootiology, National Veterinary Institute, Uppsala, Sweden .
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    A 1-year epidemiological study of campylobacters in 18 Swedish chicken farms1996In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 26, no 3-4, p. 167-185Article in journal (Refereed)
    Abstract [en]

    Broiler chickens are often intestinal carriers of Campylobacter. During processing, Campylobacter may be spread over the carcass. Thus, undercooked chicken meat, or other foods contaminated by raw chicken can act as a source of infection to humans. This study was conducted to identify risk factors for chicken flocks being colonized with Campylobacter. Eighteen chicken farms with altogether 62 chicken compartments were studied for 1 year with visits during each growing period and sampling of chicken caecal contents at slaughter. Four to six subsequent flocks were raised in each compartment during the study. A detailed questionnaire was used to record farm parameters such as building materials, feed and water equipment, hygiene and management routines. Campylobacter prevalence varied between farms, between growing periods within the farms and also during the year, with lowest prevalence during the spring. Campylobacters were isolated from 27% out of 287 flocks. Only two farms were negative at all samplings. Often the flock following a positive flock in a compartment was negative, indicating that normal cleaning and disinfecting routines are sufficient for eliminating the bacteria from the house. Usually only one serotype was found in each positive flock. Campylobacter occurrence increased with the age of the chickens at slaughter, and also with flock size.

    Univariable chi-square tests were done of the association between possible risk factors and Campylobacter prevalence. Factors associated with higher Campylobacter prevalence in flocks were lack of or diffuse hygiene barriers, increasing flock size, increasing age at slaughter, short vs. long empty periods, wet litter beds, other poultry nearby or staff handling other poultry, flocks divided before slaughter, staff loading to slaughter at several farms and occurrence of mice. Under Swedish conditions, water does not seem to be a source of infection for chickens. Origin and handling of day-old chickens, feed additives, houses and litter were not associated with higher Campylobacter prevalence.

  • 27.
    Berner-Branzell, Filip
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Carbohydrate Binding Specificity of a Variant Heliocobacter pylori BabA Adhesin2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 28.
    Biava, Pier M.
    et al.
    Scientific Institute of Research and Care Multimedica, Milano, Italy.
    Canaider, Silvia
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
    Facchin, Federica
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
    Bianconi, Eva
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
    Ljungberg, Liza
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rotilio, Domenico
    Department of Haematology, Ospedali Riuniti BMM, Reggio Calabria, Italy.
    Burigana, Fabio
    Associazione Medicina e Complessità (AMEC), Trieste, Italy.
    Ventura, Carlo
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Bologna, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy; Stem Wave Institute for Tissue Healing (SWITH), Gruppo Villa Maria (GVM) Care & Research - Ettore Sansavini Health Science Foundation, Lugo (Ravenna), Italy.
    Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy to Modulate the Fate of Normal and Pathological Human (Stem) Cells2015In: Current Pharmaceutical Biotechnology, ISSN 1389-2010, E-ISSN 1873-4316, Vol. 16, no 9, p. 782-792Article in journal (Refereed)
    Abstract [en]

    In spite of the growing body of evidence on the biology of the Zebrafish embryo and stem cells, including the use of Stem Cell Differentiation Stage Factors (SCDSFs) taken from Zebrafish embryo to impact cancer cell dynamics, comparatively little is known about the possibility to use these factors to modulate the homeostasis of normal human stem cells or to modulate the behavior of cells involved in different pathological conditions. In the present review we recall in a synthetic way the most important researches about the use of SCDSFs in reprogramming cancer cells and in modulating the high speed of multiplication of keratinocytes which is characteristic of some pathological diseases like psoriasis. Moreover we add here the results about the capability of SCDSFs in modulating the homeostasis of human adipose-derived stem cells (hASCs) isolated from a fat tissue obtained with a novel-non enzymatic method and device. In addition we report the data not yet published about a first protein analysis of the SCDSFs and about their role in a pathological condition like neurodegeneration.

  • 29.
    Blaad, Emilia
    Örebro University, School of Health Sciences.
    Tolkning av neurografisvar vid frågeställningen karpaltunnelsyndrom – en jämförelse mellan erfaren och oerfaren tolkare2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 30.
    Boknäs, Niklas
    et al.
    Department of Hematology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ramström, Sofia
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Faxälv, Lars
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lindahl, Tomas L.
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Flow cytometry-based platelet function testing is predictive of symptom burden in a cohort of bleeders2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, no 5, p. 512-519Article in journal (Refereed)
    Abstract [en]

    Platelet function disorders (PFDs) are common in patients with mild bleeding disorders (MBDs), yet the significance of laboratory findings suggestive of a PFD remain unclear due to the lack of evidence for a clinical correlation between the test results and the patient phenotype. Herein, we present the results from a study evaluating the potential utility of platelet function testing using whole-blood flow cytometry in a cohort of 105 patients undergoing investigation for MBD. Subjects were evaluated with a test panel comprising two different activation markers (fibrinogen binding and P-selectin exposure) and four physiologically relevant platelet agonists (ADP, PAR1-AP, PAR4-AP, and CRP-XL). Abnormal test results were identified by comparison with reference ranges constructed from 24 healthy controls or with the fifth percentile of the entire patient cohort. We found that the abnormal test results are predictive of bleeding symptom severity, and that the greatest predictive strength was achieved using a subset of the panel, comparing measurements of fibrinogen binding after activation with all four agonists with the fifth percentile of the patient cohort (p = 0.00008, hazard ratio 8.7; 95% CI 2.5-40). Our results suggest that whole-blood flow cytometry-based platelet function testing could become a feasible alternative for the investigation of MBDs. We also show that platelet function testing using whole-blood flow cytometry could provide a clinically relevant quantitative assessment of platelet-related hemostasis.

  • 31.
    Brander, Gustaf
    et al.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rydell, Mina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul S.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Serlachius, Eva
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 5, p. 1189-1197Article in journal (Refereed)
    Abstract [en]

    Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

  • 32.
    Breimer, Lars H.
    et al.
    Fac Med & Hlth, Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjorn K.
    Dept Med Biosci, Clin Chem, Umeå Univ, Umeå, Sweden.
    Is Ferrotoxicity a New Great Public Health Challenge?2015In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 61, no 4, p. 667-668Article in journal (Refereed)
  • 33.
    Breimer, Lars H.
    et al.
    Departments of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine, Biomedicine, Örebro University, Örebro, Sweden; Departments of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Has folate a role in the developing nervous system after birth and not just during embryogenesis and gestation?2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 3, p. 185-191Article, review/survey (Refereed)
    Abstract [en]

    It is now 30 years since the first publications stating that supplementation with folate could prevent neural tube defects appeared and 20 years since the definitive data, including prevention of other birth defects. Since then epidemiological studies and animal experiments have identified folate as a molecule at the crossroads of neural development. Fortification of food has greatly reduced the incidence of spina bifida. Much interest has focussed on long-term sequelae in children born to mothers severely deprived of folate (and other nutrients) such as during the Dutch Hunger Winter of 1944 and in poor parts of the world. In addition, deficiency in folate and B12 are increasingly discussed as a possible contributing factor in dementia and congenital orofacial and heart malformations. The year 2011 saw the publication of a study that implicated low folate intake in poorer school performance of adolescents as judged by school marks. This has enormous social implications but needs confirmation from other settings. This review assesses the current state of evidence and sets the data in context of whether folate has a role in the development and plasticity of the nervous system even after birth, with particular emphasis on childhood and adolescence.

  • 34.
    Breimer, Lars
    et al.
    Örebro University Hospital.
    Nilsson, T.
    Sverige bör bergunda ett utspel i PNAS: Sweden should contemplate article in PNAS2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 46, p. 2045-Article in journal (Refereed)
  • 35.
    Brockmöller, Scarlet F.
    et al.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Bucher, Elmar
    Medical Biotechnology, VTT Technical Research Centre of Finland, University of Turku, Turku, Finland.
    Müller, Berit M.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Budczies, Jan
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Griffin, Julian L.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Kallioniemi, Olli
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Iljin, Kristiina
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Loibl, Sibylle
    German Breast Group, GBG-Forschungs GmbH, Neu-Isenburg, Germany.
    Darb-Esfahani, Silvia
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Sinn, Bruno V.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Klauschen, Frederick
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Prinzler, Judith
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Bangemann, Nikola
    Breast Cancer Center, Charité University Hospital, Berlin, Germany.
    Ismaeel, Fakher
    Department of Gynaecology and Obstetrics, DRK Kliniken Köpenick, Berlin, Germany; Department of Gynaecology and Obstetrics, Charité University Hospital, Berlin, Germany.
    Fiehn, Oliver
    Genome Center, University of California-Davis, Davis CA, United States.
    Dietel, Manfred
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling2012In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, no 2, p. 850-60Article in journal (Refereed)
    Abstract [en]

    Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.

  • 36.
    Brolin, Malin
    Örebro University, School of Health Sciences.
    Detektion av antikroppar mot Francisella tularensis i serum med chemiluminescence och immunokromatografiskt snabbtest2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 37. Brosché, Mikael
    et al.
    Strid, Åke
    Örebro University, Department of Natural Sciences.
    Molecular events following perception of ultraviolet-B radiation by plants2003In: Physiologia Plantarum: An International Journal for Plant Biology, ISSN 0031-9317, E-ISSN 1399-3054, Vol. 117, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Exposure of plants to UV-B radiation (280–320 nm) results in changes in expression of a large number of genes. Before UV-B radiation or light of other wavelengths can give rise to a cellular response, it has to be perceived by some kind of receptor, and the information transduced via a signalling pathway to the target molecules, be it proteins in the cytoplasm

    or the genetic material in the nucleus. The perception of low levels of UV-B probably occurs via a UV-B photoreceptor followed by several different signalling pathways. These pathways include second messengers such as calcium, kinases and the catalytic formation of reactive oxygen species. High levels of UV-B, on the other hand, probably cause cellular damage

    and oxidative stress, thus activating a general stress signal transduction pathway which leads to a response similar to that which occurs after pathogen attack and other stresses. Some of the genes identified so far as being regulated by UV-B encode proteins involved in the biosynthesis of protective pigments, DNA repair and antioxidative enzymes, photosynthetic genes, cell cycle genes, and stress genes induced by other types of stimuli (i.e. pathogenesis-related proteins and senescence-induced genes). In the light of the information obtained on components necessary for UV-B-induced changes in gene expression, we propose in this mini-review a working model for UV-B perception and signal transduction. This model also takes into account dosage differences for the observations, which imply a separation into UV-B-specific and more general stress signal transduction.

  • 38.
    Budczies, Jan
    et al.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Müller, Berit M.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Brockmöller, Scarlet F.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Klauschen, Frederick
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Györffy, Balazs
    Institute of Pathology, Charité University Hospital, Berlin, Germany; Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Dietel, Manfred
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Richter-Ehrenstein, Christiane
    Interdisciplinary Breast Center, Charité University Hospital, Berlin, Germany.
    Marten, Ulrike
    Institute of Pathology, DRK Kliniken Berlin, Berlin, Germany.
    Salek, Reza M.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Griffin, Julian L.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Wohlgemuth, Gert
    Genome Center, University of California Davis, Davis CA, United States.
    Fiehn, Oliver
    Genome Center, University of California Davis, Davis CA, United States.
    Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, no 1, article id 334Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far.

    RESULTS: A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%.

    CONCLUSIONS: For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

  • 39.
    Burla, Bo
    et al.
    Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore.
    Arita, Makoto
    Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan; Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, Japan.
    Arita, Masanori
    National Institute of Genetics, Shizuoka, Japan and RIKEN Center for Sustainable Resource Science, Yokohama, Japan.
    Bendt, Anne K.
    Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore.
    Cazenave-Gassiot, Amaury
    Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    Dennis, Edward A.
    Departments of Pharmacology and Chemistry and Biochemistry, School of Medicine, University of California at San Diego, La Jolla, CA, USA.
    Ekroos, Kim
    Lipidomics Consulting Ltd., Esbo, Finland.
    Han, Xianlin
    Barshop Institute for Longevity and Aging Studies and Department of Medicine-Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
    Ikeda, Kazutaka
    Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
    Liebisch, Gerhard
    Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
    Lin, Michelle K.
    Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    Loh, Tze Ping
    Department of Laboratory Medicine, National University Hospital, Singapore.
    Meikle, Peter J.
    Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
    Orešič, Matej
    Örebro University, School of Medical Sciences. Turku Centre for Biotechnology, University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland.
    Quehenberger, Oswald
    Departments of Pharmacology and Medicine, School of Medicine, University of California at San Diego, La Jolla, CA, USA.
    Shevchenko, Andrej
    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
    Torta, Federico
    Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    Wakelam, Michael J. O.
    Babraham Institute, Cambridge, United Kingdom.
    Wheelock, Craig E.
    Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
    Wenk, Markus R.
    Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore; Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore.
    MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines2018In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 59, no 10, p. 2001-2017Article in journal (Refereed)
    Abstract [en]

    Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

  • 40.
    Bäcklund, Madeleine
    Örebro University, School of Health and Medical Sciences.
    Molekylärgenetisk typning av Propionibacterium acnes isolerade från prostata, perineum och panna hos patienter med prostatacancer2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 41.
    Bülow, Katrin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jämförelse av selektivitet för Clostridium difficile mellan två olika odlingsmedier2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 42.
    Cable, N.
    et al.
    Department of Epidemiology and Public Health, University College London, London, UK.
    Hiyoshi, Ayako
    Örebro University, School of Medical Sciences.
    Kondo, N.
    Department of Health and Social Behavior, School of Public Health, University of Tokyo, Tokyo, Japan.
    Aida, J.
    Division of International and Community Oral Health, Graduate School of Dentistry, Tohoku University, Miyagi, Japan.
    Sjöqvist, Hugo
    Kondo, K.
    Center for Preventive Medical Science, Chiba University, Chiba, Japan.
    Identifying Frail-Related Biomarkers among Community-Dwelling Older Adults in Japan: A Research Example from the Japanese Gerontological Evaluation Study2018In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 5362948Article in journal (Refereed)
    Abstract [en]

    We examined correlating clinical biomarkers for the physical aspect of frailty among community-dwelling older adults in Japan, using Japanese Gerontological Evaluation Study (JAGES). We used information from the JAGES participants (N = 3,128) who also participated in the community health screening in 2010. We grouped participants' response to the Study of Osteoporotic Fracture (SOF) Frailty Index into robust (=0), intermediate frail (=1), and frail (=2+) ones to indicate physical aspect of frailty. Independent of sex and age, results from multinomial logistic regression showed above normal albumin and below normal HDL and haemoglobin levels were positively associated with intermediate frail (RRR = 1.99, 95% CI = 1.22-3.23; RRR = 1.36, 95% CI = 1.33-1.39; RRR = 1.36, 95% CI = 1.23-1.51, resp.) and frail cases (RRR = 2.27, 95% CI = 1.91-2.70; RRR = 1.59, 95% CI = 1.51-1.68; RRR = 1.40, 95% CI = 1.28-1.52, resp.). Limited to women, above normal Hb1Ac level was similarly associated with intermediate frail and frail cases (RRR = 1.18, 95% CI = 1.02, 1.38; RRR = 2.56, 95% CI = 2.23-2.95, resp.). Use of relevant clinical biomarkers can help in assessment of older adults' physical aspect of frailty.

  • 43.
    Calles-Escandon, Jorge
    et al.
    Department of Medicine, Endocrine and Metabolism Section, University of Vermont, Burlington VT, United States; University of Vermont, College of Medicine, Burlington VT, United States.
    Sweet, Leigh M.
    Department of Medicine, Endocrine and Metabolism Section, University of Vermont, Burlington VT, United States.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska Institute, Stockholm, Sweden.
    Hirschman, Michael F.
    Joslin Diabetes Center, Boston, MA, United States.
    The membrane-associated 40 KD fatty acid binding protein(Berk's protein), a putative fatty acid transporter is present in human skeletal muscle1995In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 58, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Muscle tissue (1.1 +/- 0.1 grams) was obtained from seven healthy individuals (3 males, 4 females) using an open incision approach before and after ingestion of either 75 grams of dextrose (N=5) or water (N=2). Purified sarcolemmal membranes from the muscle were prepared using a sucrose step gradient. A polyclonal antibody raised against the purified (99%) rat hepatocyte 40 KD membrane fatty acid binding protein (mFABP-L) was used to probe for this putative transporter in the muscle membranes using Western blot. A single band at the 40 KD MW band was identified which reacted antigenically with the proteinpurified from rat livers. These response of Berk's protein 60-75 minutes after dextrose ingestion (or water) was erratic and no specific trend could be identified. Our data demonstrate that the 40 KD mFABP-L originally isolated from rat liver is also present in human skeletal muscle membrane. This protein may be involved in transport of fatty acids across the membrane of skeletal muscle, however its physiological role in human fatty acidmetabolism remains to be established.

  • 44. Canaider, S.
    et al.
    Maioli, M.
    Facchin, F.
    Bianconi, E.
    Santaniello, S.
    Pigliaru, G.
    Ljungberg, Liza U.
    Burigana, F.
    Bianchi, F.
    Olivi, E.
    Tremolada, C.
    Biava, P.M.
    Ventura, C.
    Human Stem Cell Exposure to Developmental Stage Zebrafish Extracts: a Novel Strategy for Tuning Stemness and Senescence Patterning2014In: Cell, ISSN 2329-7042, Vol. 2, no 5, article id e1226Article in journal (Refereed)
    Abstract [en]

    Background: Zebrafish exhibits extraordinary ability for tissue regeneration. Despite growing investigations dissecting the molecular underpinning of such regenerative potential, little is known about the possibility to use the chemical inventory of the zebrafishembryo to modulate human stem cell dynamics.

    Methods: Extracts from zebrafish embryo were collected at different developmental stages, referred to as ZF1, ZF2, ZF3 (early stages), and ZF4, ZF5 (late stages). Human adipose-derived stem cells (hASCs), isolated from microfractured fat tissue obtained with a novel non-enzymatic method (Lipogems), were cultured in absence or presence of each developmental stage extract. Cell viability was assessed by MTT assay. Nuclear morphology was investigated by cell-permeable dye 4’,6-DAPI. Caspase-3 activity was assessed by ELISA. Gene transcription was monitored by real-time PCR.

    Results: Late developmental stage extracts decreased cell viability and elicited caspase-3 mediated apoptosis. This effect did not involve Bax or Bcl-2 transcription. Conversely, early developmental stage ZF1 did not affect cell viability or apoptosis, albeit increasing Bax/Bcl-2mRNA ratio. ZF1 enhanced transcription of the stemness/pluripotency genes Oct-4, Sox-2and c-Myc. ZF1 also induced the transcription of TERT, encoding the catalytic subunit of telomerase, as well as the gene expression of Bmi-1, a chromatin remodeler acting as a major telomerase-independent repressor of senescence. These transcriptional responses were restricted to the action of early stage factors, since they were not elicited by late developmental stage ZF5.

    Conclusions: Exposure to early developmental stage zebrafish embryo extracts may enhance stem cell expression of multipotency and activate both telomerase-dependent and -independent antagonists of cell senescence. These outcomes may prove rewarding during prolonged expansion in culture, as it occurs in most cell therapy protocols.

  • 45. Carlsson, C.
    et al.
    Johansson, Carina B.
    Örebro University, Department of Clinical Medicine.
    Holmgren Peterson, K.
    Sul, Y. T.
    Comparisons of bone tissue formation around pure titanium implants using light- and fluorescence microscopically techniques2006Conference paper (Refereed)
  • 46.
    Carlsson, Lars
    Örebro University, Department of Clinical Medicine.
    Impedanskardiografi med Physio flow kontra ”Fick´s direkt” för beräkning av hjärtminutvolym på elitskidåkare under stakning.2007Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Trots tidigare oenighet bland forskare är den allmänna uppfattningen idag att det är hjärtminutvolymen (HMV) som är den enskilt största begränsande faktorn för maximalt syreupptag under arbete. Fortfarande råder dock osäkerhet bland arbetsfysiologer huruvida slagvolymen (SV) planar ut, minskar eller stiger vid maximalt arbete. En av de största utmaningarna inom arbetsfysiologin är utvecklandet av en tillförlitlig, billig och enkel non-invasiv utrustning i syfte att kunna mäta dessa parametrar. Detta har lett fram till metoden impedanskardiografi som baseras på motståndet av elektriska signaler som skickas genom thorax. Tidigare studier har visat på hög validitet mellan den impedanskardiografiska utrustningen Physio flowTM och den invasiva metoden ”Fick´s direkt” i vila och under cykelarbete på otränade. I detta arbete har ett första försök på elitskidåkare (n = 6) gjorts i syfte att jämföra metoderna under stakning, dessutom jämfördes resultaten av slagvolymen från impedansutrustningen mellan submaximalt och maximalt arbete. Resultatet visade att inte heller denna studie med säkerhet kunde skilja metoderna åt, vare sig under submaximalt arbete (p = 0,43) eller vid maximalt arbete (p = 0,17). Det ska dock poängteras att Fick´s beräkningsmetod modifierats i syfte att undvika katetrar genom hjärtat under maximal stakning, vilket kan ha påverkat resultatet. En intressant observation gällande SV gjordes mellan submaximal och maximal stakning. Här noterades en ökning från 150,1 till 175,5 ml (p = 0,01) vilket motsäger Åstrands klassiska ”platåteori” från 1964.

  • 47.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Ribosome specialization and its potential role in the control of protein translation and skeletal muscle size2019In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601Article, review/survey (Refereed)
    Abstract [en]

    The ribosome is typically viewed as a supramolecular complex with constitutive and invariant capacity in mediating translation of mRNA into protein. This view has been challenged by recent research revealing that ribosome composition could be heterogeneous, and this heterogeneity leads to functional ribosome specialization. This review presents the idea that ribosome heterogeneity results from changes in its various components, including variations in ribosomal protein (RP) composition, post-translational modifications of RPs, changes in ribosomal-associated proteins, alternative forms of rRNA and post-transcriptional modifications of rRNAs. Ribosome heterogeneity could be orchestrated at several levels and may depend on numerous factors, such as the subcellular location, cell type and tissue specificity, the development state, cell state, ribosome biogenesis, RP turnover, physiological stimuli and circadian rhythm. Ribosome specialization represents a completely new concept for the regulation of gene expression. Specialized ribosomes could modulate several aspects of translational control, such as mRNA translation selectivity, translation initiation, translational fidelity and translation elongation. Recent research indicates that the expression of Rpl3 is markedly increased, while that of Rpl3l is highly reduced during mouse skeletal muscle hypertrophy. Moreover, Rpl3l overexpression impairs the growth and myogenic fusion of myotubes. Although the function of Rpl3 and Rpl3l in the ribosome remains to be clarified, these findings suggest that ribosome specialization may be potentially involved in the control of protein translation and skeletal muscle size. Limited data concerning ribosome specialization are currently available in skeletal muscle. Future investigations have the potential to delineate the function of specialized ribosomes in skeletal muscle.

  • 48.
    Chaillou, Thomas
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Cheng, Arthur J.
    Karolinska Institutet, Stockholm, Sweden.
    Integrative biology is needed to understand exercise adaptions from the whole body to the cellular level2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 121, no 2, p. 598-599Article in journal (Refereed)
  • 49.
    Chaillou, Thomas
    et al.
    Center for Muscle Biology, University of Kentucky, Lexington KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    Zhang, Xiping
    Center for Muscle Biology, University of Kentucky, Lexington KY,USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    McCarthy, John J
    Center for Muscle Biology, University of Kentucky, Lexington, Kentucky; Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky.
    Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth2016In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 231, no 9, p. 1894-1902Article in journal (Refereed)
    Abstract [en]

    The ribosome has historically been considered to have no cell-specific function but rather serve in a "housekeeping" capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like (Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ∼fivefold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (-23%) and protein content (-14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (-17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth.

  • 50.
    Dammström, Magdalena
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Användning av Small interfering RNA med syftet att minska uttrycket av insulin like growth factor-1 receptor hos melanomceller2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
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