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  • 1.
    Aho, Vilma
    et al.
    Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Ollila, Hanna M
    Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Stanford University Center for Sleep Sciences, Palo Alto CA, United States.
    Kronholm, Erkki
    Department of Chronic Disease Prevention, Population Studies Unit, National Institute for Health and Welfare, Turku, Finland.
    Bondia-Pons, Isabel
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Soininen, Pasi
    Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
    Kangas, Antti J
    Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Seppälä, Ilkka
    Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
    Kettunen, Johannes
    Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland; Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
    Oikonen, Mervi
    Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
    Raitoharju, Emma
    Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Kähönen, Mika
    Department of Clinical Physiology, University of Tampere, Tampere University Hospital, Tampere, Finland.
    Viikari, Jorma S A
    Department of Medicine, University of Turku, Turku, Finland; Division of Medicine, Turku University Hospital, Turku, Finland.
    Härmä, Mikko
    Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland.
    Sallinen, Mikael
    Brain and Work Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland; Agora Center, University of Jyväskylä, Jyväskylä, Finland.
    Olkkonen, Vesa M
    Minerva Foundation Institute for Medical Research, Helsinki, Finland; Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
    Alenius, Harri
    Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
    Jauhiainen, Matti
    Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland.
    Paunio, Tiina
    Genomics and Biomarkers Unit, Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
    Lehtimäki, Terho
    Department of Clinical Chemistry, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.
    Salomaa, Veikko
    Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
    Orešič, Matej
    VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.
    Raitakari, Olli T
    Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
    Ala-Korpela, Mika
    Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Oulu University Hospital, Oulu, Finland; Computational Medicine, School of Social and Community Medicine, Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
    Porkka-Heiskanen, Tarja
    Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 24828Article in journal (Refereed)
    Abstract [en]

    Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.

  • 2.
    Alpkvist, Helena
    et al.
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infectious Diseases.
    Mölling, Paula
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Norrby-Teglund, Anna
    Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    High HMGB1 levels in sputum are related to pneumococcal bacteraemia but not to disease severity in community-acquired pneumonia2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 13428Article in journal (Refereed)
    Abstract [en]

    During bacterial infections, damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) activate immune cells. Here, we investigated whether plasma and sputum levels of High Mobility Group Box 1 (HMGB1), a prototypic DAMP, are associated with disease severity and aetiology in community-acquired pneumonia (CAP). In addition, in patients with pneumococcal CAP, the impact of the level of sputum lytA DNA load, a PAMP, was investigated. We studied patients hospitalised for bacterial CAP (n = 111), and samples were collected at admission. HMGB1 was determined by enzyme-linked immunosorbent assays, and pneumococcal lytA DNA load was determined by quantitative polymerase chain reaction. Plasma and sputum HMGB1 levels did not correlate to disease severity (pneumonia severity index or presence of sepsis), but high sputum HMGB1 level was correlated to pneumococcal aetiology (p = 0.002). In pneumococcal pneumonia, high sputum lytA DNA load was associated with respiratory failure (low PaO2/FiO2 ratio; p = 0.019), and high sputum HMGB1 level was associated with bacteraemia (p = 0.006). To conclude, high sputum HMGB1 was not associated with severe disease, but with pneumococcal bacteraemia, indicating a potential role for HMGB1 in bacterial dissemination. High sputum lytA was associated with severe disease.

  • 3.
    Amruth, C
    et al.
    Department of Molecular Physics, Lodz University of Technology, Lodz, Poland.
    Szymański, Marek
    Örebro University, School of Science and Technology. Department of Engineering and Chemical Sciences, Karlstad University, Karlstad, Sweden.
    Łuszczyńska, Beata
    Department of Molecular Physics, Lodz University of Technology, Lodz, Poland.
    Ulański, Jacek
    Department of Molecular Physics, Lodz University of Technology, Lodz, Poland.
    Inkjet Printing of Super Yellow: Ink Formulation, Film Optimization, OLEDs Fabrication, and Transient Electroluminescence2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 8493Article in journal (Refereed)
    Abstract [en]

    Inkjet printing technique allows manufacturing low cost organic light emitting diodes (OLEDs) in ambient conditions. The above approach enables upscaling of the OLEDs fabrication process which, as a result, would become faster than conventionally used vacuum based processing techniques. In this work, we use the inkjet printing technique to investigate the formation of thin active layers of well-known light emitting polymer material: Super Yellow (poly(para-phenylene vinylene) copolymer). We develop the formulation of Super Yellow ink, containing non-chlorinated solvents and allowing stable jetting. Optimization of ink composition and printing resolution were performed, until good quality films suitable for OLEDs were obtained. Fabricated OLEDs have shown a remarkable characteristics of performance, similar to the OLEDs fabricated by means of spin coating technique. We checked that, the values of mobility of the charge carriers in the printed films, measured by transient electroluminescence, are similar to the values of mobility measured in spin coated films. Our contribution provides a complete framework for inkjet printing of high quality Super Yellow films for OLEDs. The description of this method can be used to obtain efficient printed OLEDs both in academic and in industrial settings.

  • 4.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden .
    Lee, Yi-Ping
    Department of Clinical Microbiology, Virology,Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Nilsson, Emma
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Kröger, Andrea
    Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany; Institute for Microbiology, University of Magdeburg, Magdeburg, Germany.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden; The Laboratory for Molecular Medicine Sweden (MIMS), Umeå University, Umeå, Sweden.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 39265Article in journal (Refereed)
    Abstract [en]

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

  • 5.
    Brüggemann, Holger
    et al.
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Jensen, Anders
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Nazipi, Seven
    Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Bioscience, Aarhus University, Aarhus, Denmark.
    Aslan, Husnu
    Department of Bioscience, Aarhus University, Aarhus, Denmark.
    Meyer, Rikke Louise
    Department of Bioscience, Aarhus University, Aarhus, Denmark.
    Poehlein, Anja
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, Georg-August University Göttingen, Göttingen, Germany.
    Brzuszkiewicz, Elzbieta
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, Georg-August University Göttingen, Göttingen, Germany.
    Al-Zeer, Munir A.
    Department of Applied Biochemistry, Institute of Biotechnology, TU Berlin, Berlin, Germany.
    Brinkmann, Volker
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 266Article in journal (Refereed)
    Abstract [en]

    Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.

  • 6.
    Czégény, Gyula
    et al.
    Department of Plant Biology, University of Pécs, Pécs, Hungary.
    Körösi, Laszlo
    Research institute for Viticulture and Oenology, University of Pécs, Pécs, Hungary.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Hideg, Éva
    Department of Plant Biology, University of Pécs, Pécs, Hungary.
    Multiple roles for Vitamin B6in plant acclimation to UV-B2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 1259Article in journal (Refereed)
    Abstract [en]

    Direct and indirect roles of vitamin B6in leaf acclimation to supplementary UV-B radiation are shown in vitamin B6deficient Arabidopsis thalianamutant rsr4-1 and C24 wild type. Responses to 4 days of 3.9 kJ m-2d-1 biologically effective UV-B dose were compared in terms of leaf photochemistry, vitamer content, and antioxidant enzyme activities; complemented with a comprehensive study of vitamer ROS scavenging capacities. Under UV-B, rsr4-1 leaves lost more (34%) photochemical yield than C24 plants (24%). In the absence of UV-B, rsr4-1 leaves contained markedly less pyridoxal-5’-phosphate (PLP) than C24 ones, but levels increased up to the C24 contents in response to UV-B. Activities of class-III ascorbate and glutathione peroxidases increased in C24 leaves upon the UV-B treatment but not in the rsr4-1 mutant. SOD activities remained the same in C24 but decreased by more than 50% in rsr4-1 under UV-B. Although PLP was shown to be an excellent antioxidant in vitro, our results suggest that the UV-B protective role of B6 vitamers is realized indirectly, via supporting peroxidase defence rather than by direct ROS scavenging. We hypothesize that the two defence pathways are linked through the PLP-dependent biosynthesis of cystein and heme, affecting peroxidases.

  • 7.
    Elgazali, Abdelkarem A. S.
    et al.
    Trace Element Speciation Laboratory, Department of Chemistry, University of Aberdeen, Aberdeen, UK.
    Gajdosechova, Zuzana
    Trace Element Speciation Laboratory, Department of Chemistry, University of Aberdeen, Aberdeen, UK.
    Abbas, Zaigham
    LG & RD Complex, Ministry of Climate Change, Islamabad, Pakistan.
    Lombi, Enzo
    Future Industries Institute, University of South Australia, Mawson Lakes SA, Australia.
    Scheckel, Kirk G.
    Future Industries Institute, University of South Australia, Mawson Lakes SA, Australia; National Risk Management Research Laboratory, United States Environmental Protection Agency, Cincinnati OH, USA.
    Donner, Erica
    Future Industries Institute, University of South Australia, Mawson Lakes SA, Australia.
    Fiedler, Heidelore
    Örebro University, School of Science and Technology. Chemicals Branch, UN Environment PProgramme (UNEP), Division of Technology, Industry and Economics (DTIE), Chatelaine, Switzerland.
    Feldmann, Jörg
    Trace Element Speciation Laboratory, Department of Chemistry, University of Aberdeen, Aberdeen, UK.
    Krupp, Eva M.
    Trace Element Speciation Laboratory, Department of Chemistry, University of Aberdeen, Aberdeen.
    Reactive gaseous mercury is generated from chloralkali factories resulting in extreme concentrations of mercury in hair of workers2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 3675Article in journal (Refereed)
    Abstract [en]

    Occupational exposure of chloralkali workers to highly concentrated mercury (Hg) vapour has been linked to an increased risk of renal dysfunction and behavioural changes. It is generally believed that these workers are exposed to elemental Hg, which is used in abundance during the production process however, the lack in analytical techniques that would allow for identification of gaseous Hg species poses a challenge, which needs to be addressed in order to reach a consensus. Here, we present the results from simulated exposure studies, which provide sound evidence of higher adsorption rate of HgCl2 than Hg-0 and its irreversible bonding on the surface of hair. We found that chloralkali workers were exposed to HgCl2, which accumulated in extremely high concentrations on the hair surface, more than 1,000 times higher than expected from unexposed subjects and was positively correlated with Hg levels in the finger- and toenails.

  • 8.
    Fang, Xin
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wang, Lei
    Department of Oral & Maxillofacial-Head & Neck Oncology, the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
    Wu, Chunhua
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Shi, Huijing
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Zhou, Zhijun
    School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, China.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sex Hormones, Gonadotropins, and Sex Hormone-binding Globulin in Infants Fed Breast Milk, Cow Milk Formula, or Soy Formula2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4332Article in journal (Refereed)
    Abstract [en]

    Measurement of endogenous hormones in early life is important to investigate the effects of hormonally active environmental compounds. To assess the possible hormonal effects of different feeding regimens in different sample matrices of infants, 166 infants were enrolled from two U.S hospitals between 2006 and 2009. The children were classified into exclusive soy formula, cow milk formula or breast milk regimens. Urine, saliva and blood samples were collected over the first 12 months of life. Estradiol, estrone, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels were measured in the three matrices. Lower estradiol and LH levels were found in urine and saliva samples of soy formula-fed boys compared to cow formula-fed boys. Higher LH level was found in urine samples of soy formula-fed girls compared to cow formula-fed girls. However, we found neither a neonatal testosterone rise in the boys nor a gender-specific difference in testosterone levels, which suggests that urinary testosterone levels may not accurately reflect blood levels during mini-puberty. Nevertheless, our study shows that blood, urine and saliva samples are readily collectible and suitable for multi-hormone analyses in children and allow examination of hypotheses concerning endocrine effects from dietary compounds.

  • 9.
    Fu, Jianjie
    et al.
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
    Gao, Yan
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
    Wang, Thanh
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
    Liang, Yong
    Jianghan University, Wuhan, China.
    Zhang, Aiqian
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
    Wang, Yawei
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
    Jiang, Guibin
    State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
    Elevated levels of perfluoroalkyl acids in family members of occupationally exposed workers: the importance of dust transfer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 9313Article in journal (Refereed)
    Abstract [en]

    The exposure pathways of perfluoroalkyl acids (PFAAs) to humans are still not clear because of the complex living environment, and few studies have simultaneously investigated the bioaccumulative behaviour of different PFAAs in humans. In this study, serum, dust, duplicate diet, and other matrices were collected around a manufacturing plant in China, and homologous series of PFAAs were analysed. PFAA levels in dust and serum of local residents in this area were considerably higher than those in non-polluted area. Although dietary intake was the major exposure pathway in the present study, dust ingestion played an important role in this case. Serum PFAAs in local residents was significantly correlated with dust PFAAs levels in their living or working microenvironment. Serum PFAAs and dust PFAAs were significantly higher in family members of occupational workers (FM) than in ordinary residents (OR) (p<0.01). After a careful analysis of the PFAAs exposure pathway, a potential pathway in addition to direct dust ingestion was suggested: PFAAs might transferred from occupational worker's clothes to dinners via cooking processes. The bioaccumulative potential of PFHxS and PFOS were higher than other PFAAs, which suggested a substantial difference between the bioaccumulative ability of perfluorinated sulfonic acids and perfluorinated carboxylic acids.

  • 10.
    Ganda Mall, John Peter
    et al.
    Örebro University, School of Medical Sciences.
    Löfvendahl, Lisa
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Keita, Å. V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 13404Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (β)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. β-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.

  • 11.
    Golparian, Daniel
    et al.
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Donà, Valentina
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Institute of Veterinary Bacteriology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
    Sánchez-Busó, Leonor
    Pathogen Genomics, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
    Foerster, Sunniva
    WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Harris, Simon
    Pathogen Genomics, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom.
    Endimiani, Andrea
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Low, Nicola
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Antimicrobial resistance prediction and phylogenetic analysis of Neisseria gonorrhoeae isolates using the Oxford Nanopore MinION sequencer2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 17596Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is common, compromising gonorrhoea treatment internationally. Rapid characterisation of AMR strains could ensure appropriate and personalised treatment, and support identification and investigation of gonorrhoea outbreaks in nearly real-time. Whole-genome sequencing is ideal for investigation of emergence and dissemination of AMR determinants, predicting AMR, in the gonococcal population and spread of AMR strains in the human population. The novel, rapid and revolutionary long-read sequencer MinION is a small hand-held device that generates bacterial genomes within one day. However, accuracy of MinION reads has been suboptimal for many objectives and the MinION has not been evaluated for gonococci. In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants. Nevertheless, using an in house-developed CLC Genomics Workbench including de novo assembly and optimised BLAST algorithms, we show that 2D ONT-derived sequences can be used for accurate prediction of decreased susceptibility or resistance to recommended antimicrobials in gonococcal isolates. We also show that the 2D ONT-derived sequences are useful for rapid phylogenomic-based molecular epidemiological investigations, and, in hybrid assemblies with Illumina sequences, for producing contiguous assemblies and finished reference genomes.

  • 12.
    Ho, Peh Joo
    et al.
    Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
    Tan, Chuen Seng
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
    Shawon, Shajedur Rahman
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Old road campus, Oxford, UK.
    Eriksson, Mikael
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Lim, Li Yan
    Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore.
    Miao, Hui
    Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore, Singapore.
    Png, Eileen
    Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore, Singapore.
    Chia, Kee Seng
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
    Hartman, Mikael
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Czene, Kamila
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Hall, Per
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden; Department of Oncology, Södersjukhuset, Stockholm, Sweden.
    Li, Jingmei
    Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore, Singapore; Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden; Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore.
    Comparison of self-reported and register-based hospital medical data on comorbidities in women2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 3527Article in journal (Refereed)
    Abstract [en]

    Breast cancer patients commonly present with comorbidities which are known to influence treatment decisions and survival. We aim to examine agreement between self-reported and register-based medical records (National Patient Register [NPR]). Ascertainment of nine conditions, using individually-linked data from 64,961 women enrolled in the Swedish KARolinska MAmmography Project for Risk Prediction of Breast Cancer (KARMA) study. Agreement was assessed using observed proportion of agreement (overall agreement), expected proportion of agreement, and Cohen's Kappa statistic. Two-stage logistic regression models taking into account chance agreement were used to identify potential predictors of overall agreement. High levels of overall agreement (i.e. ≥86.6%) were observed for all conditions. Substantial agreement (Cohen's Kappa) was observed for myocardial infarction (0.74), diabetes (0.71) and stroke (0.64) between self-reported and NPR data. Moderate agreement was observed for preeclampsia (0.51) and hypertension (0.46). Fair agreement was observed for heart failure (0.40) and polycystic ovaries or ovarian cysts (0.27). For hyperlipidemia (0.14) and angina (0.10), slight agreement was observed. In most subgroups we observed negative specific agreement of >90%. There is no clear reference data source for ascertainment of conditions. Negative specific agreement between NPR and self-reported data is consistently high across all conditions.

  • 13.
    Ingberg, Edvin
    et al.
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Dock, Hua
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Division of Neuro and Inflammation Science, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medicine, Örebro University, Sweden. Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University; Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Linköping, Sweden; Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, County Council of Örebro, Örebro, Sweden.
    Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21086Article in journal (Refereed)
    Abstract [en]

    Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

  • 14.
    Ingberg, Edvin
    et al.
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, Elvar
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Theodorsson, Annette
    Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Neuroscience, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, Region Örebro Län, Örebro, Sweden.
    Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20228Article in journal (Refereed)
    Abstract [en]

    The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.

  • 15.
    Jelenkovic, Aline
    et al.
    Department of Social Research, University of Helsinki, Helsinki, Finland; Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV/EHU, Leioa, Spain.
    Tuvblad, Catherine
    Örebro University, School of Law, Psychology and Social Work.
    Silventoinen, Karri
    Department of Social Research, University of Helsinki, Helsinki, Finland; Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
    Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 28496Article in journal (Refereed)
    Abstract [en]

    Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.

  • 16.
    Kharlyngdoh, Joubert Banjop
    et al.
    Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Centre, Chicago, USA.
    Pradhan, Ajay
    Örebro University, School of Science and Technology.
    Olsson, Per-Erik
    Örebro University, School of Science and Technology.
    Androgen receptor modulation following combination exposure to brominated flame-retardants2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 4843Article in journal (Refereed)
    Abstract [en]

    Endocrine disrupting compounds can interfere with androgen receptor (AR) signaling and disrupt steroidogenesis leading to reproductive failure. The brominated flame-retardant (BFR) 1, 2-dibromo-4-(1, 2-dibromoethyl) cyclohexane (TBECH), is an agonist to human, chicken and zebrafish AR. Recently another group of alternative BFRs, allyl 2, 4, 6-tribromophenyl ether (ATE), and 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether (DPTE) along with its metabolite 2-bromoallyl 2, 4, 6-tribromophenyl ether (BATE) were identified as potent human AR antagonists. These alternative BFRs are present in the environment. The aim of the present study was to determine the effect of mixed exposures to the AR agonist and the AR antagonists at environmentally relevant concentrations. In vitro reporter luciferase assay showed that the AR antagonists, when present at concentration higher than TBECH, were able to inhibit TBECH-mediated AR activity. These AR antagonists also promoted AR nuclear translocation. In vitro gene expression analysis in the non-tumorigenic human prostate epithelial cell RWPE1 showed that TBECH induced AR target genes whereas DPTE repressed these genes. Further analysis of steroidogenic genes showed that TBECH up-regulated most of the genes while DPTE down-regulated the same genes. The results indicate that when TBECH and DPTE are present together they will antagonize each other, thereby reducing their individual effects.

  • 17.
    Klarström-Engström, Kristin
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical trial unit.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Human renal fibroblasts are strong immunomobilizers during a urinary tract infection mediated by uropathogenic Escherichia coli2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 2296Article in journal (Refereed)
    Abstract [en]

    To prevent the onset of urosepsis and reduce mortality, a better understanding of how uropathogenic Escherichia coli (UPEC) manages to infiltrate the bloodstream through the kidneys is needed. The present study elucidates if human renal interstitial fibroblasts are part of the immune response limiting a UPEC infection, or if UPEC has the ability to modulate the fibroblasts for their own gain. Microarray results showed that upregulated genes were associated with an activated immune response. We also found that chemokines released from renal fibroblasts upon a UPEC infection could be mediated by LPS and triacylated lipoproteins activating the TLR2/1, TLR4, MAPK, NF-κB and PKC signaling pathways. Furthermore, UPEC was also shown to be able to adhere and invade renal fibroblasts, mediated by the P-fimbriae. Furthermore, it was found that renal fibroblasts were more immunoreactive than renal epithelial cells upon a UPEC infection. However, both renal fibroblasts and epithelial cells were equally efficient at inducing neutrophil migration. In conclusion, we have found that human renal fibroblasts can sense UPEC and mobilize a host response with neutrophil migration. This suggests that renal fibroblasts are not only structural cells that produce and regulate the extracellular matrix, but also highly immunoreactive cells.

  • 18.
    König, Julia
    et al.
    Örebro University, School of Medical Sciences.
    Holster, Savanne
    Örebro University, School of Medical Sciences.
    Maaike, Bruins
    DSM Biotechnology Centre, Delft, Netherlands.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 13100Article in journal (Refereed)
    Abstract [en]

    The Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten in healthy subjects when added to an intragastrically infused meal. The current study investigated the efficacy of AN-PEP in a physiological meal setting. In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome, i.e. success rate of high dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum, was achieved in 10 of 13 comparisons. In the stomach, gluten levels were reduced from 176.9 (median, interquartile range 73.5–357.8) to 22.0 (10.6–50.8, p = 0.001) in the high dose and to 25.4 μg × min/ml (16.4–43.7, p = 0.001) in the low dose. In the duodenum, gluten levels were reduced from 14.1 (8.3–124.7) in the placebo to 6.3 (3.5–19.8, p = 0.019) in the high dose and to 7.4 μg × min/ml in the low dose (3.8–12.0, p = 0.015). Thus even in a physiological meal setting, AN-PEP significantly degraded most gluten in the stomach before it entered the duodenum.

  • 19.
    Lamichhane, Santosh
    et al.
    Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Ahonen, Linda
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Dyrlund, Thomas Sparholt
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Kemppainen, Esko
    Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Siljander, Heli
    Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
    Hyöty, Heikki
    Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
    Ilonen, Jorma
    Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland; Clinical Microbiology, Turku University Hospital, Turku, Finland.
    Toppari, Jorma
    Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland; Department of Pediatrics, Turku University Hospital, Turku, Finland.
    Veijola, Riitta
    Department of Paediatrics, PEDEGO Research Unit, University of Oulu Finland, Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Hyötyläinen, Tuulia
    Örebro University, School of Science and Technology.
    Knip, Mikael
    Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland; Folkhälsan Research Center, Helsinki, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
    Dynamics of Plasma Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes - Type 1 Diabetes Prediction and Prevention Study (DIPP)2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 10635Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that distinct lipidomic signatures characterize children who progressed to islet autoimmunity or overt T1D, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.

  • 20.
    Luo, Kai
    et al.
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Centre of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
    Li, Runkui
    College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China; State Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Science, Beijing, China.
    Li, Wenjing
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Centre of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
    Wang, Zongshuang
    Chinese Research Academy of Environmental Sciences, Beijing, China.
    Ma, Xinming
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Centre of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
    Zhang, Ruiming
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Centre of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
    Fang, Xin
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wu, Zhenglai
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Centre of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
    Cao, Yang
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Xu, Qun
    Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China; Centre of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
    Acute Effects of Nitrogen Dioxide on Cardiovascular Mortality in Beijing: An Exploration of Spatial Heterogeneity and the District-specific Predictors2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 2, article id 38328Article in journal (Refereed)
    Abstract [en]

    The exploration of spatial variation and predictors of the effects of nitrogen dioxide (NO2) on fatal health outcomes is still sparse. In a multilevel case-crossover study in Beijing, China, we used mixed Cox proportional hazard model to examine the citywide effects and conditional logistic regression to evaluate the district-specific effects of NO2 on cardiovascular mortality. District-specific predictors that could be related to the spatial pattern of NO2 effects were examined by robust regression models. We found that a 10 μg/m(3) increase in daily mean NO2 concentration was associated with a 1.89% [95% confidence interval (CI): 1.33-2.45%], 2.07% (95% CI: 1.23-2.91%) and 1.95% (95% CI: 1.16-2.72%) increase in daily total cardiovascular (lag03), cerebrovascular (lag03) and ischemic heart disease (lag02) mortality, respectively. For spatial variation of NO2 effects across 16 districts, significant effects were only observed in 5, 4 and 2 districts for the above three outcomes, respectively. Generally, NO2 was likely having greater adverse effects on districts with larger population, higher consumption of coal and more civilian vehicles. Our results suggested independent and spatially varied effects of NO2 on total and subcategory cardiovascular mortalities. The identification of districts with higher risk can provide important insights for reducing NO2 related health hazards.

  • 21.
    Marschall, Hanns-Ulrich
    et al.
    Sahlgrenska Academy, Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
    Henriksson, Ida
    Örebro University, School of Medical Sciences.
    Lindberg, Sara
    Department of Internal Medicine, Skaraborg Hospital, Skövde, Sweden.
    Söderdahl, Fabian
    Statisticon AB, Uppsala, Sweden.
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden.
    Wahlin, Staffan
    Karolinska University Hospital Huddinge, Department of Gastroenterology and Hepatology, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Incidence, prevalence, and outcome of primary biliary cholangitis in a nationwide Swedish population-based cohort2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11525Article in journal (Refereed)
    Abstract [en]

    Available epidemiological data on primary biliary cholangitis (PBC) in Sweden originate from regional studies in the 1980s and may not reflect modern day PBC. We aimed to estimate incidence and prevalence, survival and death causes, and gender differences in PBC. We used international classification of disease (ICD) codes to identify patients with PBC in inpatient and outpatient registries 1987-2014 who were then linked to the Swedish cause of death, cancer and prescribed drug registries. Each PBC patient was matched with 10 reference individuals from the general population. In sensitivity analyses, we examined PBC patients identified through clinical patient records from Karolinska, Sahlgrenska and Orebro University Hospitals. We identified 5,350 adults with PBC. Prevalence of PBC increased steadily from 5.0 (1987) to 34.6 (2014) per 100,000 inhabitants whereas the yearly incidence rate was relatively constant with a median of 2.6 per 100,000 person-years, with a female: male gender ratio of 4:1. Compared to reference individuals, PBC individuals aged 15-39 years at diagnosis had a substantially higher risk of death (Hazard Ratio [HR] 12.7, 95% Confidence Interval [CI] 8.3-19.5) than those diagnosed between 40-59 (HR 4.1, 95% CI 3.7-4.5) and > 60 (HR 3.7, 95% CI 3.5-3.9) years of age. Relative risks of mortality were highest in men. In conclusion, we found that recorded prevalence of PBC in Sweden has increased substantially during the last 30 years although incidence has been stable. Patients diagnosed in young adulthood were at a 12.7-fold increased risk of death, and male PBC patients had worse prognosis.

  • 22.
    Mushtaq, Muhammad
    et al.
    Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
    Jensen, Lasse
    Linköping University, Linköping, Sweden.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Grygoruk, Oleksandr V.
    Clinic Boris, Kyiv, Ukraine.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Kashuba, Vladimir
    Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
    Kashuba, Elena
    Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine (NASU), Kyiv, Ukraine.
    The MRPS18-2 protein levels correlate with prostate tumor progression and it induces CXCR4-dependent migration of cancer cells2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 2268Article in journal (Refereed)
    Abstract [en]

    We have earlier found abnormal expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) in endometrial cancer, compared to the expression in hyperplasia and in normal endometrium. Here we report that expression of S18-2 was increased with disease progression in clinical specimens of prostate cancer (PCa). The level of induction of epithelial to mesenchymal cell transition (EMT) correlated with the expression level of S18-2 in PCa cell lines. Moreover, cells acquired increased ability of migration upon S18-2 overexpression, as was evaluated in zebrafish embryo model and in trans-well assay. We found that this is due to increased CXCR4 cell surface expression. Neutralizing CXCR4 protein or abrogating S18-2 expression in cells significantly reduced their migratory ability directed toward CXCL12. The mRNA expression of TWIST2, encoding one of transcription factors that induce EMT upon CXCR4 increase, positively correlated with the S18-2 protein level. Together, these data suggest that the S18-2 protein induces EMT through the TWIST2/E-cadherin signalling and, consequently, CXCR4-mediated migration of PCa cells.

  • 23.
    Nowak, Christoph
    et al.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Hetty, Susanne
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Castillejo-Lopez, Casimiro
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ganna, Andrea
    Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Cook, Naomi L.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Broeckling, Corey D.
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA.
    Prenni, Jessica E.
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA.
    Shen, Xia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
    Giedraitis, Vilmantas
    Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
    Ärnlöv, Johan
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Berne, Christian
    Department of Medical Sciences, Clinical Diabetology and Metabolism, Uppsala University, Uppsala, Sweden.
    Sundström, Johan
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Fall, Tove
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 8691Article in journal (Refereed)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 ± 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10- and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10- or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

  • 24.
    Park, Wook Ha
    et al.
    Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
    Kang, Sora
    Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
    Lee, Hong Kyu
    Department of Internal Medicine, College of Medicine, Eulji University, Seoul, South Korea.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Pak, Youngmi Kim
    Department of Physiology, College of Medicine, Kyung Hee University, Seoul, South Korea.
    Lind, Lars
    Department of Medicine, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs)2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9383Article in journal (Refereed)
    Abstract [en]

    Metabolic syndrome and mitochondrial dysfunction have been linked to elevated serum levels of persistent organic pollutants (POPs). However, it is not clear which specific POPs contribute to aryl hydrocarbon receptor (AhR)-dependent bioactivity or inhibit mitochondrial function in human subjects. Here, we measured the cumulative bioactivity of AhR ligand mixture (AhR bioactivity) and the effects on mitochondrial function (ATP concentration) in recombinant Hepa1c1c7 cells incubated with raw serum samples obtained from 911 elderly subjects in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Plasma concentrations of 30 POPs and plastic chemicals have previously been determined in the same PIVUS subjects. Linear regression analysis demonstrated that total toxic equivalence (TEQ) values and polychlorinated biphenyls (PCBs) were significantly correlated with AhR bioactivity (positively) and ATP concentration (negatively). Serum AhR bioactivities were positively associated with some PCBs, regardless of their dioxin-like properties, but only dioxin-like PCBs stimulated AhR bioactivity. By contrast, PCBs mediated a reduction in ATP content independently of their dioxin-like properties. This study suggests that AhR bioactivity and ATP concentrations in serum-treated cells may be valuable surrogate biomarkers of POP exposure and could be useful for the estimation of the effects of POPs on human health.

  • 25.
    Pervishko, Anastasiia A.
    et al.
    ITMO University, Saint Petersburg, Russia.
    Baglai, Mikhail I.
    ITMO University, Saint Petersburg, Russia; Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
    Eriksson, Olle
    Örebro University, School of Science and Technology. Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
    Yudin, Dmitry
    ITMO University, Saint Petersburg, Russia.
    Another view on Gilbert damping in two-dimensional ferromagnets2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17148Article in journal (Refereed)
    Abstract [en]

    A keen interest towards technological implications of spin-orbit driven magnetization dynamics requests a proper theoretical description, especially in the context of a microscopic framework, to be developed. Indeed, magnetization dynamics is so far approached within Landau-Lifshitz-Gilbert equation which characterizes torques on magnetization on purely phenomenological grounds. Particularly, spin-orbit coupling does not respect spin conservation, leading thus to angular momentum transfer to lattice and damping as a result. This mechanism is accounted by the Gilbert damping torque which describes relaxation of the magnetization to equilibrium. In this study we work out a microscopic Kubo-Streda formula for the components of the Gilbert damping tensor and apply the elaborated formalism to a two-dimensional Rashba ferromagnet in the weak disorder limit. We show that an exact analytical expression corresponding to the Gilbert damping parameter manifests linear dependence on the scattering rate and retains the constant value up to room temperature when no vibrational degrees of freedom are present in the system. We argue that the methodology developed in this paper can be safely applied to bilayers made of non- and ferromagnetic metals, e.g., CoPt.

  • 26.
    Rejnö, Gustaf
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Obstetrics and Gynaecology Unit, Söderjukhuset, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Öberg, Sara
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Larsson, Kjell
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Saltvedt, Sissel
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Obstetrics & Gynaecology Unit, Karolinska University Hospital, Stockholm, Sweden.
    Brew, Bronwyn K.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Maternal anxiety, depression and asthma and adverse pregnancy outcomes: a population based study2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 13101Article in journal (Refereed)
    Abstract [en]

    To evaluate associations between maternal anxiety or depression and adverse pregnancy outcomes, taking possible familial confounding and interaction with asthma into account, we conducted a cohort study of all singleton births in Sweden 2001-2013. We retrieved information about pregnancy, diagnoses of anxiety/depression, asthma, and prescribed medication from the Swedish Medical Birth, National Patient, and Prescribed Drug Registers. We estimated associations with regression models, performed cousin and sibling comparisons, and calculated interactions. In 950 301 identified pregnancies; 5.9% had anxiety/depression and 4.0% had asthma. Anxiety/depression was associated with adverse pregnancy outcomes (e.g. preeclampsia, adjusted Odds Ratio 1.17 (95% Confidence Interval 1.12, 1.22), instrumental delivery (1.14 (1.10, 1.18)), elective (1.62 (1.57, 1.68)) and emergency (1.32 (1.28, 1.35)) caesarean section (CS)). Their children had lower birth weight (-54 g (-59, -49)) and shorter gestational age (-0.29 weeks (-0.31, -0.28)). Associations were not confounded by familial factors and asthma did not modify the effect of anxiety/depression for outcomes other than elective CS, p < 0.001. In women with anxiety/depression diagnosis, untreated women had higher odds of elective CS compared to women on medication (1.30 (1.17, 1.43)). In conclusion, anxiety/depression should be considered when evaluating pregnant women's risk of complications such as preeclampsia and non-vaginal deliveries.

  • 27.
    Romagnoni, Alberto
    et al.
    Centre de recherche sur l’inflammation UMR 1149, Inserm - Université Paris Diderot, Paris, France; Data Team, Département d’informatique de l’ENS, École normale supérieure, CNRS, PSL Research University, Paris, France.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Whittaker, P.
    The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
    Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10351Article in journal (Refereed)
    Abstract [en]

    Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.

  • 28.
    Slezak, Julia K.
    et al.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Theodorsson, Elvar
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Testosterone-like immunoreactivity in hair measured in minute sample amounts - a competitive radioimmunoassay with an adequate limit of detection2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17636Article in journal (Refereed)
    Abstract [en]

    The concentrations of testosterone deposited in hair during hair growth may provide a retrospective reflection of the concentrations of bioactive testosterone in plasma. The objective of this study was to develop a radioimmunoassay with a sufficiently low limit of detection to measure the testosterone-like immunoreactivity in smaller hair samples (5 mg) than used in earlier studies, and to compare three different extraction procedures. The competitive radioimmunoassay consisted of a polyclonal antiserum (immunogen testosterone-7 alpha-BSA) and a radioligand synthesised from testosterone-3-CMO-histamine. The within-assay and total coefficients of variation in the working range was 3% and 4.5%, respectively. The limit of detection was 0.87 pg/mL, which is equivalent to 0.12 pg/mg testosterone in 5 mg of hair. The concentration of testosterone-like immunoreactivity in hair samples was 1.23 (SD 0.47) pg/mg in women and 2.67 (SD 0.58) pg/mg in men (pulverised hair). Significantly improved precision was found when pulverised hair was used compared to non-pulverised hair. Our data indicate that pulverisation of the hair prior to hormone extraction is crucial. Detection limits fit for the intended purpose are achievable with 5 mg samples of hair.

  • 29.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Effects of high and low 17β-estradiol doses on focal cerebral ischemia: negative results2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, article id 3111Article in journal (Refereed)
    Abstract [en]

    The reasons why some animal studies indicate that estrogens increase focal cerebral ischemic damage while others show estrogen-induced neuroprotection has hitherto not been fully elucidated. Recent evidence indicates that discrepancies in hormone administration paradigms, resulting in highly different serum hormone concentrations, may account for the dichotomy. The current study aimed to test this hypothesis. Sixty ovariectomized female rats were randomized into three groups differing in 17β-estradiol regimens, and transient focal cerebral ischemia was subsequently induced. All animals were subjected to a small functional testing battery, and three days after MCAo they were sacrificed for infarct size assessment. Infarct sizes did not differ between groups, however clear discrepancies were seen in body weight and feeding behavior. In comparison to sham-operated animals, ovariectomized rats rapidly increased in body weight, whereas the opposite was seen in rats receiving 17beta-estradiol. The weight gain in the ovariectomized rats was paralleled by an increased food intake.

  • 30.
    Södergren, Anna Linnea
    et al.
    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.
    Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 1441Article in journal (Refereed)
    Abstract [en]

    It is recognised that platelets respond differently to activation, where a subpopulation of platelets adopt a procoagulant phenotype while others are aggregatory. However, it has not been thoroughly tested whether these subpopulations will remain in maximally activated samples, or if they are merely a result of different platelet sensitivities to agonist activation. Here platelets were activated with gradually increasing concentrations of thrombin and/or the GPVI agonist cross-linked collagen-related peptide (CRP-XL). Platelet activation was investigated using a novel six-colour flow cytometry protocol evaluating exposure of phosphatidylserine, active conformation of the fibrinogen receptor αIIbβ3, α-granule and lysosomal release (P-selectin and LAMP-1 exposure), mitochondrial membrane integrity and platelet fragmentation. Upon activation by CRP-XL or thrombin+CRP-XL, platelets formed three differently sized subpopulations. Normal-sized platelets showed high exposure of aggregatory active αIIbβ3 and intact mitochondria, while the smaller platelets and platelet fragments showed high exposure of procoagulant phosphatidylserine. The distribution of platelets between the differently sized subpopulations remained stable despite high agonist concentrations. All three were still present after 30 and 60 min of activation, showing that all platelets will not have the same characteristics even after maximal stimulation. This suggests that platelet subpopulations with distinct activation patterns exist within the total platelet population.

  • 31.
    Tian, Li-Yun
    et al.
    Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.
    Levämäki, Henrik
    Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.
    Eriksson, Olle
    Örebro University, School of Science and Technology. Department of Physics and Astronomy, Division of Materials Theory, Uppsala University, Uppsala, Sweden.
    Kokko, Kalevi
    Department of Physics and Astronomy, University of Turku, Turku, Finland; Turku University Centre for Materials and Surfaces (MatSurf), Turku, Finland.
    Nagy, Ágnes
    Department of Theoretical Physics, University of Debrecen, Debrecen, Hungary.
    Délczeg-Czirják, Erna Krisztina
    Department of Physics and Astronomy, Division of Materials Theory, Uppsala University, Uppsala, Sweden.
    Vitos, Levente
    Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden; Department of Physics and Astronomy, Division of Materials Theory, Uppsala University, Uppsala, Sweden; Research Institute for Solid State Physics and Optics, Wigner Research Center for Physics, Budapest, Hungary.
    Density Functional Theory description of the order-disorder transformation in Fe-Ni2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 8172Article in journal (Refereed)
    Abstract [en]

    The thermodynamic ordering transformation of tetragonal FeNi system is investigated by the Exact Muffin-Tin Orbitals (EMTO) method. The tetragonal distortion of the unit cell is taken into account and the free energy is calculated as a function of long-range order and includes the configurational, vibrational, electronic and magnetic contributions. We find that both configurational and vibrational effects are important and that the vibrational effect lowers the predicted transformation temperature by about 480 K compared to the value obtained merely from the configurational free energy. The predicted temperature is in excellent agreement with the experimental value when all contributions are taken into account. We also perform spin dynamics calculations for the magnetic transition temperature and find it to be in agreement with the experiments. The present research opens new opportunities for quantum-mechanical engineering of the chemical and magnetic ordering in tetrataenite.

  • 32.
    Ugalde-Morales, Emilio
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Li, Jingmei
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
    Humphreys, Keith
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Yang, Haomin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Hall, Per
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Czene, Kamila
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Common shared genetic variation behind decreased risk of breast cancer in celiac disease2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5942Article in journal (Refereed)
    Abstract [en]

    There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = -0.17, s.e. 0.05, P < 0.001) and overlap (Ppermuted < 0.001) between celiac disease and breast cancer. Using individuallevel genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (P-CD < 1.00E-05, P-BC <= 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.

  • 33.
    Vechetti, Ivan J
    et al.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA; Department of Morphology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil.
    Wen, Yuan
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Chaillou, Thomas
    Örebro University, School of Health Sciences.
    Murach, Kevin A.
    Department of Rehabilitation Sciences, College of Health Sciences, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Alimov, Alexander P.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Figueiredo, Vandre C.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Department of Rehabilitation Sciences, College of Health Sciences, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Dal-Pai-Silva, Maeli
    Department of Morphology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil.
    McCarthy, John J.
    Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
    Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 5483Article in journal (Refereed)
    Abstract [en]

    We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to ~50% of WT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle.

  • 34.
    Wang, Mo-Jin
    et al.
    Sichuan University, Chengdu, China; Linköping University, Linköping, Sweden.
    Ping, Jie
    Linköping University, Linköping, Sweden.
    Li, Yuan
    Sichuan University, Chengdu, China.
    Adell, Gunnar
    Linköping University, Linköping, Sweden.
    Arbman, Gunnar
    Linköping University, Linköping, Sweden.
    Nodin, Bjorn
    Lund University, Lund, Sweden.
    Meng, Wen-Jian
    Sichuan University, Chengdu, China; Linköping University, Linköping, Sweden.
    Zhang, Hong
    Örebro University, School of Medicine, Örebro University, Sweden.
    Yu, Yong-Yang
    Sichuan University, Chengdu, China.
    Wang, Cun
    Sichuan University, Chengdu, China.
    Yang, Lie
    Sichuan University, Chengdu, China.
    Zhou, Zong-Guang
    Sichuan University, Chengdu, China.
    Sun, Xiao-Feng
    Sichuan University, Chengdu, China; Linköping University, Linköping, Sweden.
    The prognostic factors and multiple biomarkers in young patients with colorectal cancer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 10645Article in journal (Refereed)
    Abstract [en]

    The incidence of colorectal cancer (CRC) in young patients (<= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

  • 35.
    Wikström, Sverre
    et al.
    Örebro University, School of Medical Sciences. Department of Health Sciences, Karlstad University, Karlstad, Sweden.
    Lindh, Christian H.
    Division of Occupational and environmental Medicine, Lund University, Lund, Sweden.
    Shu, Huan
    Department of Health Sciences, Karlstad University, Karlstad, Sweden; Department of environmental Science and Analytical chemistry, Stockholm University, Stockholm, Sweden .
    Bornehag, Carl-Gustaf
    Department of Health Sciences, Karlstad University, Karlstad, Sweden; Department of Preventive Medicine, icahn School of Medicine at Mount Sinai, New York, USA.
    Early pregnancy serum levels of perfluoroalkyl substances and risk of preeclampsia in Swedish women2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 9179Article in journal (Refereed)
    Abstract [en]

    Preeclampsia is a major cause of maternal and fetal morbidity. Emerging research shows an association with environmental exposures. The present aim was to investigate associations between early pregnancy serum levels of perfluoroalkyl substances (PFAS) and preeclampsia. Within the Swedish SELMA study, eight PFAS were measured at median 10 gestational weeks and cases of preeclampsia were postnatally identified from registers. Associations between individual PFAS and preeclampsia were assessed, adjusting for parity, age, weight and smoking. Out of 1,773 women in the study group, 64 ( 3.6%), developed preeclampsia. A doubling of PFOS and PFNA exposure, corresponding to an inter-quartile increase, was associated with an increased risk for preeclampsia of about 38-53% respectively. Serum PFOS within the highest quartile was associated with an odds ratio of 2.68 ( CI 95%: 1.17-6.12), equal to the increased risk associated with nulliparity, when compared to exposure in the first quartile. The same associations were identified, although with higher risk estimates, in analyses restricted to nulliparous women. For other PFAS, there were no associations. In conclusion and consistent with limited previous research only on PFOS, increasing serum levels of PFOS and PFNA during early pregnancy were associated with a clinically relevant risk of preeclampsia, adjusting for established confounders.

  • 36.
    Wu, Min
    et al.
    Chalmers University of Technology, Gothenburg, Sweden.
    Farkas, Daniel
    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; School of Science and Technology, Örebro University, Örebro, Sweden.
    Eriksson, Leif A.
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Proline 411 biases the conformation of the intrinsically disordered plant UVR8 photoreceptor C27 domain altering the functional properties of the peptide2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 818Article in journal (Refereed)
    Abstract [en]

    UVR8 (UV RESISTANCE LOCUS 8) is a UV-B photoreceptor responsible for initiating UV-B signalling in plants. UVR8 is a homodimer in its signalling inactive form. Upon absorption of UV radiation, the protein monomerizes into its photoactivated state. In the monomeric form, UVR8 binds the E3 ubiquitin ligase COP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1), triggering subsequent UV-B-dependent photomorphogenic development in plants. Recent in vivoexperiments have shown that the UVR8 C-terminal region (aa 397-423; UVR8C27) alone is sufficient to regulate the activity of COP1. In this work, CD spectroscopy and NMR experiments showed that the UVR8C27domain was non-structured but gained secondary structure at higher temperatures leading to increased order. Bias-exchange metadynamics simulations were also performed to evaluate the free energy landscape of UVR8C27. An inverted free energy landscape was revealed, with a disordered structure in the global energy minimum. Flanking the global energy minimum, more structured states were found at higher energies. Furthermore, stabilization of the low energy disordered state was attributed to a proline residue, P411, as evident from P411A mutant data. P411 is also a key residue in UVR8 binding to COP1. UVR8C27is therefore structurally competent to function as a molecular switch for interaction of UVR8 with different binding partners since at higher free energies different structural conformations are being induced in this peptide. P411 has a key role for this function.

  • 37.
    Zengin, Gulis
    et al.
    Chalmers University of Technology, Göteborg, Sweden.
    Johansson, Goran
    Chalmers University of Technology, Göteborg, Sweden.
    Johansson, Peter
    Örebro University, School of Science and Technology. Chalmers University of Technology, Göteborg, Sweden.
    Antosiewicz, Tomasz J.
    Chalmers University of Technology, Göteborg, Sweden; University of Warsaw, Warsaw, Poland.
    Käll, Mikael
    Chalmers University of Technology, Göteborg, Sweden.
    Shegai, Timur
    Chalmers University of Technology, Göteborg, Sweden.
    Approaching the strong coupling limit in single plasmonic nanorods interacting with J-aggregates2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, article id 3074Article in journal (Refereed)
    Abstract [en]

    We studied scattering and extinction of individual silver nanorods coupled to the J-aggregate form of the cyanine dye TDBC as a function of plasmon - exciton detuning. The measured single particle spectra exhibited a strongly suppressed scattering and extinction rate at wavelengths corresponding to the J-aggregate absorption band, signaling strong interaction between the localized surface plasmon of the metal core and the exciton of the surrounding molecular shell. In the context of strong coupling theory, the observed "transparency dips" correspond to an average vacuum Rabi splitting of the order of 100 meV, which approaches the plasmon dephasing rate and, thereby, the strong coupling limit for the smallest investigated particles. These findings could pave the way towards ultra-strong light-matter interaction on the nanoscale and active plasmonic devices operating at room temperature.

  • 38.
    Zhang, Boxi
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sirsjö, Allan
    Örebro University, School of Medicine, Örebro University, Sweden. Sch Hlth Sci, Dept Clin Med, Univ Orebro, Orebro, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medicine, Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden.
    Transcriptional profiling of human smooth muscle cells infected with gingipain and fimbriae mutants of Porphyromonas gingivalis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21911Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis (P. gingivalis) is considered to be involved in the development of atherosclerosis. However, the role of different virulence factors produced by P. gingivalis in this process is still uncertain. The aim of this study was to investigate the transcriptional profiling of human aortic smooth muscle cells (AoSMCs) infected with wild type, gingipain mutants or fimbriae mutants of P. gingivalis. AoSMCs were exposed to wild type (W50 and 381), gingipain mutants (E8 and K1A), or fimbriae mutants (DPG-3 and KRX-178) of P. gingivalis. We observed that wild type P. gingivalis changes the expression of a considerable larger number of genes in AoSMCs compare to gingipain and fimbriae mutants, respectively. The results from pathway analysis revealed that the common differentially expressed genes for AoSMCs infected by 3 different wild type P. gingivalis strains were enriched in pathways of cancer, cytokine-cytokine receptor interaction, regulation of the actin cytoskeleton, focal adhesion, and MAPK signaling pathway. Disease ontology analysis showed that various strains of P. gingivalis were associated with different disease profilings. Our results suggest that gingipains and fimbriae, especially arginine-specific gingipain, produced by P. gingivalis play important roles in the association between periodontitis and other inflammatory diseases, including atherosclerosis.

  • 39.
    Ågren, Richard
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Johanna
    Örebro University, School of Medical Sciences. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Århem, Peter
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Closed and open state dependent block of potassium channels cause opposing effects on excitability - a computational approach2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 8175Article in journal (Refereed)
    Abstract [en]

    Block of voltage-gated potassium (Kv) channels has been demonstrated to affect neuronal activity described as increasing excitability. The effect has been associated with a closed-state dependent block. However, the block of Kv channels in e.g. local anesthetic and antiarrhythmics, is open state-dependent. Since the reduced excitability in this case mainly is due to sodium channel block, the role of the Kv channel block is concealed. The present investigation aims to analyse the specific role of state-dependent Kv channel block for excitability. Using a computational approach, with introduced blocked states in the Kv channel of the Frankenhaeuser-Huxley axon membrane model, we calculated the effects on threshold, firing and presynaptic Ca influx. The Ca influx was obtained from an N-type Cav channel model linked to the Frankenhaeuser-Huxley membrane. The results suggested that a selective block of open Kv channels decreased the rate of repetitive firing and the consequent Ca influx, thus challenging the traditional view. In contrast, presence of a closed-state block, increased the firing rate and the Ca influx. These findings propose that Kv channel block may either increase or decrease cellular excitability, thus highlighting the importance of further investigating the role of state-specific blocking mechanisms.

1 - 39 of 39
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