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  • 301.
    Nie, Junsheng
    et al.
    Lanzhou University.
    Stevens, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Song, Yougui
    Chinese Academy of Sciences.
    King, John
    University of Rhode Island.
    Zhang, Rui
    Lanzhou University.
    Ji, Shunchuan
    Lanzhou University.
    Gong, Lisha
    Lanzhou University.
    Cares, Danielle
    University of Rhode Island.
    Pacific freshening drives Pliocene cooling and Asian monsoon intensification2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 5474-Article in journal (Refereed)
    Abstract [en]

    The monsoon is a fundamental component of Earth's climate. The Pliocene warm period is characterized by long-term global cooling yet concurrent monsoon dynamics are poorly known. Here we present the first fully quantified and calibrated reconstructions of separate Pliocene air temperature and East Asian summer monsoon precipitation histories on the Chinese Loess Plateau through joint analysis of loess/red clay magnetic parameters with different sensitivities to air temperature and precipitation. East Asian summer monsoon precipitation shows an intensified trend, paradoxically at the same time that climate cooled. We propose a hitherto unrecognized feedback where persistently intensified East Asian summer monsoon during the late Pliocene, triggered by the gradual closure of the Panama Seaway, reinforced late Pliocene Pacific freshening, sea-ice development and ice volume increase, culminating in initiation of the extensive Northern Hemisphere glaciations of the Quaternary Ice Age. This feedback mechanism represents a fundamental reinterpretation of the origin of the Quaternary glaciations and the impact of the monsoon.

  • 302.
    Nilsson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Peric, Alexandra
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
    Strimfors, Marie
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
    Goodwin, Richard J. A.
    AstraZeneca Cambridge, Mass Spectrometry Imaging, Innovat Med & Early Dev, Drug Safety & Metab, Cambridge, England..
    Hayes, Martin A.
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden..
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hilgendorf, Constanze
    AstraZeneca Gothenburg, Cardiovasc & Metab Dis, Innovat Med & Early Dev, Gothenburg, Sweden.;AstraZeneca Gothenburg, Innovat Med & Early Dev, Drug Safety & Metab, Safety & ADME Translat Sci, Gothenburg, Sweden..
    Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6352Article in journal (Refereed)
    Abstract [en]

    Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

  • 303.
    Nohr, Anne Cathrine
    et al.
    Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark..
    Jespers, Willem
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Shehata, Mohamed A.
    Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark..
    Floryan, Leonard
    Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Vladimir Prelog Weg 1-5-10, CH-8093 Zurich, Switzerland..
    Isberg, Vignir
    Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark..
    Andersen, Kirsten Bayer
    Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark..
    Åqvist, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Gutiérrez-de-Terán, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Bräuner-Osborne, Hans
    Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark..
    Gloriam, David E.
    Univ Copenhagen, Dept Drug Design & Pharmacol, Univ Pk 2, DK-2100 Copenhagen, Denmark..
    The GPR139 reference agonists 1a and 7c, and tryptophan and phenylalanine share a common binding site2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1128Article in journal (Refereed)
    Abstract [en]

    GPR139 is an orphan G protein-coupled receptor expressed in the brain, in particular in the habenula, hypothalamus and striatum. It has therefore been suggested that GPR139 is a possible target for metabolic disorders and Parkinson's disease. Several surrogate agonist series have been published for GPR139. Two series published by Shi et al. and Dvorak et al. included agonists 1a and 7c respectively, with potencies in the ten-nanomolar range. Furthermore, Isberg et al. and Liu et al. have previously shown that tryptophan (Trp) and phenylalanine (Phe) can activate GPR139 in the hundred-micromolar range. In this study, we produced a mutagenesis-guided model of the GPR139 binding site to form a foundation for future structure-based ligand optimization. Receptor mutants studied in a Ca2+ assay demonstrated that residues F109(3x33), H187(5x43), W241(6x48) and N271(7x38), but not E108(3x32), are highly important for the activation of GPR139 as predicted by the receptor model. The initial ligand-receptor complex was optimized through free energy perturbation simulations, generating a refined GPR139 model in agreement with experimental data. In summary, the GPR139 reference surrogate agonists 1a and 7c, and the endogenous amino acids L-Trp and L-Phe share a common binding site, as demonstrated by mutagenesis, ligand docking and free energy calculations.

  • 304.
    Nordin, Love Engstrom
    et al.
    Karolinska Univ Hosp Huddinge, Dept Diagnost Med Phys, Stockholm, Sweden.;Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Moller, Marika Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, KIDS, Danderyd Hosp, Dept Clin Sci, Solnavagen 1, S-17177 Solna, Sweden..
    Julin, Per
    Karolinska Inst, KIDS, Danderyd Hosp, Dept Clin Sci, Solnavagen 1, S-17177 Solna, Sweden.;Stora Skondal Fdn, Neurol Rehabil Clin, Stockholm, Sweden..
    Bartfai, Aniko
    Karolinska Inst, KIDS, Danderyd Hosp, Dept Clin Sci, Solnavagen 1, S-17177 Solna, Sweden..
    Hashim, Farouk
    Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden..
    Li, Tie-Qiang
    Karolinska Univ Hosp Huddinge, Dept Diagnost Med Phys, Stockholm, Sweden.;Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Post mTBI fatigue is associated with abnormal brain functional connectivity2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 21183Article in journal (Refereed)
    Abstract [en]

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system.

  • 305.
    Nordling, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Brännström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Carlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lu, Bo
    St Vincents Hosp Melbourne, Immunol Res Ctr, Melbourne, Vic, Australia.
    Salvaris, Evelyn
    St Vincents Hosp Melbourne, Immunol Res Ctr, Melbourne, Vic, Australia.
    Wanders, Alkwin
    Umea Univ, Dept Med Biosci, Umea, Sweden.
    Buijs, Jos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Cowan, Peter J.
    Univ Melbourne, St Vincents Hosp Melbourne, Immunol Res Ctr, Melbourne, Vic, Australia;Univ Melbourne, Dept Med, Melbourne, Vic, Australia.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Magnusson, Peetra U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Enhanced protection of the renal vascular endothelium improves early outcome in kidney transplantation: Preclinical investigations in pig and mouse2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5220Article in journal (Refereed)
    Abstract [en]

    Ischemia reperfusion injury is one of the major complications responsible for delayed graft function in kidney transplantation. Applications to reduce reperfusion injury are essential due to the widespread use of kidneys from deceased organ donors where the risk for delayed graft function is especially prominent. We have recently shown that coating of inflamed or damaged endothelial cells with a unique heparin conjugate reduces thrombosis and leukocyte recruitment. In this study we evaluated the binding capacity of the heparin conjugate to cultured human endothelial cells, to kidneys from brain-dead porcine donors, and to murine kidneys during static cold storage. The heparin conjugate was able to stably bind cultured endothelial cells with high avidity, and to the renal vasculature of explanted kidneys from pigs and mice. Treatment of murine kidneys prior to transplantation reduced platelet deposition and leukocyte infiltration 24 hours post-transplantation, and significantly improved graft function. The present study thus shows the benefits of enhanced protection of the renal vasculature during cold storage, whereby increasing the antithrombotic and anti-adhesive properties of the vascular endothelium yields improved renal function early after transplantation.

  • 306.
    Novoselova, Iuliia P.
    et al.
    Univ Duisburg Essen, Fac Phys, D-47057 Duisburg, Germany.;Univ Duisburg Essen, Ctr Nanointegrat CENIDE, D-47057 Duisburg, Germany..
    Petruhins, Andrejs
    Linkoping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys, SE-58183 Linkoping, Sweden..
    Wiedwald, Ulf
    Univ Duisburg Essen, Fac Phys, D-47057 Duisburg, Germany.;Univ Duisburg Essen, Ctr Nanointegrat CENIDE, D-47057 Duisburg, Germany.;Natl Univ Sci & Technol MISIS, Moscow 119049, Russia..
    Ingason, Arni Sigurdur
    Linkoping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys, SE-58183 Linkoping, Sweden.;Grein Res, Ehf Dunhaga 5, Reykjavik, Iceland..
    Hase, Thomas
    Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England..
    Magnus, Fridrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics. Univ Iceland, Sci Inst, Dunhaga 3, IS-107 Reykjavik, Iceland.
    Kapaklis, Vassilios
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Palisaitis, Justinas
    Linkoping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys, SE-58183 Linkoping, Sweden..
    Spasova, Marina
    Univ Duisburg Essen, Fac Phys, D-47057 Duisburg, Germany.;Univ Duisburg Essen, Ctr Nanointegrat CENIDE, D-47057 Duisburg, Germany..
    Farle, Michael
    Univ Duisburg Essen, Fac Phys, D-47057 Duisburg, Germany.;Univ Duisburg Essen, Ctr Nanointegrat CENIDE, D-47057 Duisburg, Germany.;Immanuel Kant Baltic Fed Univ, Ctr Functionalized Magnet Mat FunMagMa, Kaliningrad, Russia..
    Rosen, Johanna
    Linkoping Univ, Dept Phys Chem & Biol IFM, Thin Film Phys, SE-58183 Linkoping, Sweden..
    Salikhov, Ruslan
    Univ Duisburg Essen, Fac Phys, D-47057 Duisburg, Germany.;Univ Duisburg Essen, Ctr Nanointegrat CENIDE, D-47057 Duisburg, Germany.;Russian Acad Sci, Zavoisky Phys Tech Inst, Kazan 420029, Russia..
    Large uniaxial magnetostriction with sign inversion at the first order phase transition in the nanolaminated Mn2GaC MAX phase2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 2637Article in journal (Refereed)
    Abstract [en]

    In 2013, a new class of inherently nanolaminated magnetic materials, the so called magnetic MAX phases, was discovered. Following predictive material stability calculations, the hexagonal Mn2GaC compound was synthesized as hetero-epitaxial films containing Mn as the exclusive M-element. Recent theoretical and experimental studies suggested a high magnetic ordering temperature and non-collinear antiferromagnetic (AFM) spin states as a result of competitive ferromagnetic and antiferromagnetic exchange interactions. In order to assess the potential for practical applications of Mn2GaC, we have studied the temperature-dependent magnetization, and the magnetoresistive, magnetostrictive as well as magnetocaloric properties of the compound. The material exhibits two magnetic phase transitions. The Neel temperature is T-N similar to 507 K, at which the system changes from a collinear AFM state to the paramagnetic state. At T-t = 214 K the material undergoes a first order magnetic phase transition from AFM at higher temperature to a non-collinear AFM spin structure. Both states show large uniaxial c-axis magnetostriction of 450 ppm. Remarkably, the magnetostriction changes sign, being compressive (negative) above T-t and tensile (positive) below the T-t. The sign change of the magnetostriction is accompanied by a sign change in the magnetoresistance indicating a coupling among the spin, lattice and electrical transport properties.

  • 307.
    Nowak, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Castillejo-Lopez, Casimiro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Cook, Naomi L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Shen, Xia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, 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.

  • 308.
    Ny, Sofia
    et al.
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Alfred Nobels Alle 10, S-14152 Stockholm, Sweden;Publ Hlth Agcy Sweden, Nobels Vag 18, S-17182 Stockholm, Sweden.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Salemi, Marco
    Univ Florida, Dept Pathol, Emerging Pathogens Inst, POB 100009, Gainesville, FL 32610 USA.
    Giske, Christian G.
    Karolinska Inst, Dept Lab Med, Div Clin Microbiol, Alfred Nobels Alle 10, S-14152 Stockholm, Sweden.
    Genome and plasmid diversity of Extended-Spectrum beta-Lactamase-producing Escherichia coli ST131-tracking phylogenetic trajectories with Bayesian inference2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10291Article in journal (Refereed)
    Abstract [en]

    Clonal lineages of ESBL (Extended-Spectrum beta-Lactamase)-producing E. coli belonging to sequence type 131 (ST131) have disseminated globally during the last 30 years, leading to an increased prevalence of resistance to fluoroquinolones and extended-spectrum cephalosporins in clinical isolates of E. coli. We aimed to study if Swedish ESBL-producing ST131 isolates originated from single or multiple introductions to the population by assessing the amount of genetic variation, on chromosomal and plasmid level, between Swedish and international E. coli ST131. Bayesian inference of Swedish E. coli ST131 isolates (n = 29), sequenced using PacBio RSII, together with an international ST131 dataset showed that the Swedish isolates were part of the international ST131 A, C1 and C2 clades. Highly conserved plasmids were identified in three clusters although they were separated by several years, which indicates a strong co-evolution between some ST131 lineages and specific plasmids. In conclusion, the tight clonal relationship observed within the ST131 clades, together with highly conserved plasmids, challenges investigation of strain transmission events. A combination of few SNPs on a genome-wide scale and an epidemiological temporospatial link, are needed to track the spread of the ST131 subclones.

  • 309.
    Nyberg, Lena K.
    et al.
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Quaderi, Saair
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden.;Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Emilsson, Gustav
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden.;Chalmers, Dept Appl Phys, Gothenburg, Sweden..
    Karami, Nahid
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden..
    Lagerstedt, Erik
    Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Muller, Vilhelm
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Noble, Charleston
    Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Hammarberg, Susanna
    Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Nilsson, Adam N.
    Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Sjoberg, Fei
    Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden..
    Fritzsche, Joachim
    Chalmers, Dept Appl Phys, Gothenburg, Sweden..
    Kristiansson, Erik
    Univ Gothenburg, Dept Math Sci, Chalmers Univ Technol, Gothenburg, Sweden..
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ambjörnsson, Tobias
    Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Rapid identification of intact bacterial resistance plasmids via optical mapping of single DNA molecules2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 30410Article in journal (Refereed)
    Abstract [en]

    The rapid spread of antibiotic resistance - currently one of the greatest threats to human health according to WHO - is to a large extent enabled by plasmid-mediated horizontal transfer of resistance genes. Rapid identification and characterization of plasmids is thus important both for individual clinical outcomes and for epidemiological monitoring of antibiotic resistance. Toward this aim, we have developed an optical DNA mapping procedure where individual intact plasmids are elongated within nanofluidic channels and visualized through fluorescence microscopy, yielding barcodes that reflect the underlying sequence. The assay rapidly identifies plasmids through statistical comparisons with barcodes based on publicly available sequence repositories and also enables detection of structural variations. Since the assay yields holistic sequence information for individual intact plasmids, it is an ideal complement to next generation sequencing efforts which involve reassembly of sequence reads from fragmented DNA molecules. The assay should be applicable in microbiology labs around the world in applications ranging from fundamental plasmid biology to clinical epidemiology and diagnostics.

  • 310.
    Obrador, Biel
    et al.
    Univ Barcelona, Dept Evolutionary Biol Ecol & Environm Sci, Av Diagonal 643, E-08028 Barcelona, Spain..
    von Schiller, Daniel
    Univ Girona, Catalan Inst Water Res ICRA, Sci & Technol Pk,Emili Grahit 101, Girona 17003, Spain.;Univ Basque Country, Fac Sci & Technol, Dept Plant Biol & Ecol, Apdo 644, Bilbao 48080, Spain..
    Marce, Rafael
    Univ Girona, Catalan Inst Water Res ICRA, Sci & Technol Pk,Emili Grahit 101, Girona 17003, Spain..
    Gomez-Gener, Lluis
    Univ Barcelona, Dept Evolutionary Biol Ecol & Environm Sci, Av Diagonal 643, E-08028 Barcelona, Spain.;Umea Univ, Dept Ecol & Environm Sci, Linnaeus Vag 6, S-90187 Umea, Sweden..
    Koschorreck, Matthias
    UFZ Helmholtz Ctr Environm Res, Dept Lake Res, Bruckstr 3a, D-39114 Magdeburg, Germany..
    Borrego, Carles
    Univ Girona, Catalan Inst Water Res ICRA, Sci & Technol Pk,Emili Grahit 101, Girona 17003, Spain.;Univ Girona, Inst Aquat Ecol, Grp Mol Microbial Ecol, Campus Montilivi, Girona 17071, Spain..
    Catalan, Nuria
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Univ Barcelona, Dept Evolutionary Biol Ecol & Environm Sci, Av Diagonal 643, E-08028 Barcelona, Spain.;Univ Girona, Catalan Inst Water Res ICRA, Sci & Technol Pk,Emili Grahit 101, Girona 17003, Spain..
    Dry habitats sustain high CO2 emissions from temporary ponds across seasons2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3015Article in journal (Refereed)
    Abstract [en]

    Despite the increasing understanding of the magnitude and drivers of carbon gas emissions from inland waters, the relevance of water fluctuation and associated drying on their dynamics is rarely addressed. Here, we quantified CO2 and CH4 fluxes from a set of temporary ponds across seasons. The ponds were in all occasion net CO2 emitters irrespective of the presence or absence of water. While the CO2 fluxes were in the upper range of emissions for freshwater lentic systems, CH4 fluxes were mostly undetectable. Dry habitats substantially contributed to these emissions and were always a source of CO2, whereas inundated habitats acted either as a source or a sink of atmospheric CO2 along the year. Higher concentrations of coloured and humic organic matter in water and sediment were linked to higher CO2 emissions. Composition of the sediment microbial community was related both to dissolved organic matter concentration and composition, but we did not find a direct link with CO2 fluxes. The presence of methanogenic archaea in most ponds suggested the potential for episodic CH4 production and emission. Our results highlight the need for spatially and temporally inclusive approaches that consider the dry phases and habitats to characterize carbon cycling in temporary systems.

  • 311. Obreht, Igor
    et al.
    Hambach, Ulrich
    Veres, Daniel
    Zeeden, Christian
    Bösken, Janina
    Stevens, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Markovic, Slobodan B.
    Klasen, Nicole
    Brill, Dominik
    Burow, Christoph
    Lehmkuhl, Frank
    Shift of large-scale atmospheric systems over Europe during late MIS 3 and implications for Modern Human dispersal2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5848Article in journal (Refereed)
    Abstract [en]

    Understanding the past dynamics of large-scale atmospheric systems is crucial for our knowledge of the palaeoclimate conditions in Europe. Southeastern Europe currently lies at the border between Atlantic, Mediterranean, and continental climate zones. Past changes in the relative influence of associated atmospheric systems must have been recorded in the region’s palaeoarchives. By comparing high-resolution grain-size, environmental magnetic and geochemical data from two loess-palaeosol sequences in the Lower Danube Basin with other Eurasian palaeorecords, we reconstructed past climatic patterns over Southeastern Europe and the related interaction of the prevailing large-scale circulation modes over Europe, especially during late Marine Isotope Stage 3 (40,000–27,000 years ago). We demonstrate that during this time interval, the intensification of the Siberian High had a crucial influence on European climate causing the more continental conditions over major parts of Europe, and a southwards shift of the Westerlies. Such a climatic and environmental change, combined with the Campanian Ignimbrite/Y-5 volcanic eruption, may have driven the Anatomically Modern Human dispersal towards Central and Western Europe, pointing to a corridor over the Eastern European Plain as an important pathway in their dispersal.

  • 312.
    Ohgaki, Ryuichi
    et al.
    Osaka University, Graduate School of Medicine, Department of Bio-system Pharmacology.
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. The University of Tokyo, Department of Bioengineering.
    Hayashi, Daichi
    Osaka University, Graduate School of Medicine, Department of Bio-system Pharmacology.
    Quan, Lili
    Osaka University, Graduate School of Medicine, Department of Bio-system Pharmacology.
    Okuda, Suguru
    Osaka University, Graduate School of Medicine, Department of Bio-system Pharmacology.
    Nagamori, Shushi
    Osaka University, Graduate School of Medicine, Department of Bio-system Pharmacology.
    Takai, Madoka
    The University of Tokyo, Department of Bioengineering.
    Kanai, Yoshikatsu
    Osaka University, Graduate School of Medicine, Department of Bio-system Pharmacology.
    Ratiometric fluorescence imaging of cell surface pH by poly(ethylene glycol)-phospholipid conjugated with fluorescein isothiocyanate2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17484Article in journal (Refereed)
    Abstract [en]

    Various physiological and pathological processes are accompanied with the alteration of pH at extracellular juxtamembrane region. Accordingly, the methods to analyze the cell surface pH have been demanded in biological and medical sciences. In this study, we have established a novel methodology for cell surface pH imaging using poly(ethylene glycol)-phospholipid (PEG-lipid) as a core structure of ratiometric fluorescent probes. PEG-lipid is a synthetic amphiphilic polymer originally developed for the cell surface modification in transplantation therapy. Via its hydrophobic alkyl chains of the phospholipid moiety, PEG-lipid is, when applied extracellularly, spontaneously inserted into the plasma membrane and retained at the surface of the cells. We have demonstrated that the PEG-lipid conjugated with fluorescein isothiocyanate (FITC-PEG-lipid) can be used as a sensitive and reversible cell-surfacea-nchored pH probe between weakly alkaline and acidic pH with an excellent spatiotemporal resolution. The remarkably simple procedure for cell-surface labeling with FITC-PEG-lipid would also be advantageous when considering its application to high-throughput in vitro assay. This study further indicates that various probes useful for the investigation of juxtamembrane environments could also be developed by using PEG-lipid as the core structure for bio-membrane anchoring.

  • 313.
    Okamoto, Kenta
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Miyazaki, Naoyuki
    Natl Inst Physiol Sci, Okazaki, Aichi, Japan..
    Larsson, Daniel S. D.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Kobayashi, Daisuke
    Natl Inst Infect Dis, Dept Med Entomol, Tokyo, Japan..
    Svenda, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Mühlig, Kerstin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Maia, Filipe R. N. C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Gunn, Laura H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Isawa, Haruhiko
    Natl Inst Infect Dis, Dept Med Entomol, Tokyo, Japan..
    Kobayashi, Mutsuo
    Natl Inst Infect Dis, Dept Med Entomol, Tokyo, Japan..
    Sawabe, Kyoko
    Natl Inst Infect Dis, Dept Med Entomol, Tokyo, Japan..
    Murata, Kazuyoshi
    Natl Inst Physiol Sci, Okazaki, Aichi, Japan..
    Hajdu, Janos
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    The infectious particle of insect-borne totivirus-like Omono River virus has raised ridges and lacks fibre complexes2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 33170Article in journal (Refereed)
    Abstract [en]

    Omono River virus (OmRV) is a double-stranded RNA virus isolated from Culex mosquitos, and it belongs to a group of unassigned insect viruses that appear to be related to Totiviridae. This paper describes electron cryo-microscopy (cryoEM) structures for the intact OmRV virion to 8.9 angstrom resolution and the structure of the empty virus-like-particle, that lacks RNA, to 8.3 angstrom resolution. The icosahedral capsid contains 120-subunits and resembles another closely related arthropod-borne totivirus-like virus, the infectious myonecrosis virus (IMNV) from shrimps. Both viruses have an elevated plateau around their icosahedral 5-fold axes, surrounded by a deep canyon. Sequence and structural analysis suggests that this plateau region is mainly composed of the extended C-terminal region of the capsid proteins. In contrast to IMNV, the infectious form of OmRV lacks extensive fibre complexes at its 5-fold axes as directly confirmed by a contrast-enhancement technique, using Zernike phase-contrast cryo-EM. Instead, these fibre complexes are replaced by a short "plug" structure at the five-fold axes of OmRV. OmRV and IMNV have acquired an extracellular phase, and the structures at the five-fold axes may be significant in adaptation to cell-to-cell transmission in metazoan hosts.

  • 314.
    Okamoto, Kenta
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Miyazaki, Naoyuki
    NIPS, Okazaki, Aichi 4448585, Japan..
    Song, Chihong
    NIPS, Okazaki, Aichi 4448585, Japan..
    Maia, Filipe
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Reddy, Hemanth K.N.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Abergel, Chantal
    CNRS, UMR 7256, IMM FR 3479, Struct & Genom Informat Lab, F-13288 Marseille, France..
    Claverie, Jean-Michel
    CNRS, UMR 7256, IMM FR 3479, Struct & Genom Informat Lab, F-13288 Marseille, France.;Aix Marseille Univ, F-13288 Marseille, France.;AP HM, F-13005 Marseille, France..
    Hajdu, Janos
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics. Inst Phys AS CR, Vvi, Na Slovance 2, Prague 18221 8, Czech Republic..
    Svenda, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Murata, Kazuyoshi
    NIPS, Okazaki, Aichi 4448585, Japan..
    Structural variability and complexity of the giant Pithovirus sibericum particle revealed by high-voltage electron cryo-tomography and energy-filtered electron cryo-microscopy2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13291Article in journal (Refereed)
    Abstract [en]

    The Pithoviridae giant virus family exhibits the largest viral particle known so far, a prolate spheroid up to 2.5 mu m in length and 0.9 mu m in diameter. These particles show significant variations in size. Little is known about the structure of the intact virion due to technical limitations with conventional electron cryo-microscopy (cryo-EM) when imaging thick specimens. Here we present the intact structure of the giant Pithovirus sibericum particle at near native conditions using high-voltage electron cryo-tomography (cryo-ET) and energy-filtered cryo-EM. We detected a previously undescribed low-density outer layer covering the tegument and a periodical structuring of the fibres in the striated apical cork. Energy-filtered Zernike phase-contrast cryo-EM images show distinct substructures inside the particles, implicating an internal compartmentalisation. The density of the interior volume of Pithovirus particles is three quarters lower than that of the Mimivirus. However, it is remarkably high given that the 600 kbp Pithovirus genome is only half the size of the Mimivirus genome and is packaged in a volume up to 100 times larger. These observations suggest that the interior is densely packed with macromolecules in addition to the genomic nucleic acid.

  • 315.
    Olausson, Karl Holmberg
    et al.
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden..
    Elsir, Tamador
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden..
    Goudarzi, Kaveh Moazemi
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden..
    Nister, Monica
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden..
    Lindstrom, Mikael S.
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Karolinska Univ Hosp Solna, SE-17176 Stockholm, Sweden.;Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Sci Life Lab, SE-17121 Stockholm, Sweden..
    NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival and maintain nucleolar shape2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16495Article in journal (Refereed)
    Abstract [en]

    Glioblastoma (grade IV glioma) is the most common and aggressive adult brain tumor. A better understanding of the biology of glioblastoma cells is crucial to identify molecular targets stimulating cell death. NPM1 (nucleophosmin) is a multifunctional chaperone that plays an important role in cancer development. Herein, NPM1 was analyzed by immunohistochemistry in human astrocytic gliomas. NPM1 was detected in all tumors but with a significantly higher staining intensity in grade IV than in low grade tumors. Depletion of NPM1 had only modest effects on the viability of U251MG, U1242MG, and U343MGa Cl2:6 glioma cells, despite alterations in nucleolar morphology. Glioma cell cultures depleted of NPM1 exposed to micromolar levels of actinomycin D were more prone to cell death (apoptosis) compared to cultures retaining NPM1. We had previously found that NPM1 binds to linker histone H1.5. Here we could show that silencing of H1.5 triggered glioma cell apoptosis as evidenced by a marked increase in both the numbers of cleaved caspase-3(+) cells and in the amounts of cleaved PARP. Enforced expression of NPM1 suppressed apoptosis in H1.5 depleted glioma cells. Although our studies would suggest little effectiveness of targeting NPM1 alone there could be potential using it as a combination treatment.

  • 316.
    Olivenza, David R.
    et al.
    Univ Seville, Fac Biol, Dept Genet, Apartado 1095, E-41080 Seville, Spain.
    Nicoloff, Hervé
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Antonia Sanchez-Romero, Maria
    Univ Seville, Fac Biol, Dept Genet, Apartado 1095, E-41080 Seville, Spain.
    Cota, Ignacio
    Univ Seville, Fac Biol, Dept Genet, Apartado 1095, E-41080 Seville, Spain;UB, UAB, IRTA, Ctr Res Agr Genom,CSIC, Campus UAB, Barcelona 08193, Spain.
    Andersson, Dan I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Casadesus, Josep
    Univ Seville, Fac Biol, Dept Genet, Apartado 1095, E-41080 Seville, Spain.
    A portable epigenetic switch for bistable gene expression in bacteria2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11261Article in journal (Refereed)
    Abstract [en]

    We describe a portable epigenetic switch based on opvAB, a Salmonella enterica operon that undergoes bistable expression under DNA methylation control. A DNA fragment containing the opvAB promoter and the opvAB upstream regulatory region confers bistability to heterologous genes, yielding OFF and ON subpopulations. Bistable expression under opvAB control is reproducible in Escherichia coli, showing that the opvAB switch can be functional in a heterologous host. Subpopulations of different sizes can be produced at will using engineered opvAB variants. Controlled formation of antibiotic-resistant and antibiotic-susceptible subpopulations may allow use of the opvAB switch in the study of bacterial heteroresistance to antibiotics.

  • 317.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zhou, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Zhukovsky, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hogenkamp, Pleunie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nikontovic, Lamia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Resting-state brain connectivity changes in obese women after Roux-en-Y gastric bypass surgery: A longitudinal study2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 6616Article in journal (Refereed)
    Abstract [en]

    Bariatric surgery is an effective method to rapidly induce weight loss in severely obese people, however its impact on brain functional connectivity after longer periods of follow-up is yet to be assessed. We investigated changes in connectivity in 16 severely obese women one month before, one month after and one year after Roux-en-Y gastric bypass surgery (RYGB). 12 lean controls were also enrolled. Resting-state fMRI was acquired for all participants following an overnight fast and after a 260 kcal load. Connectivity between regions involved in food-related saliency attribution and reward-driven eating behavior was stronger in presurgery patients compared to controls, but progressively weakened after follow-up. At one year, changes in networks related to cognitive control over eating and bodily perception also occurred. Connectivity between regions involved in emotional control and social cognition had a temporary reduction early after treatment but had increased again after one year of follow-up. Furthermore, we could predict the BMI loss by presurgery connectivity in areas linked to emotional control and social interaction. RYGBP seems to reshape brain functional connectivity, early affecting cognitive control over eating, and these changes could be an important part of the therapeutic effect of bariatric surgery.

  • 318.
    Onuţ-Brännström, Ioana
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Benjamin, Mitchell
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Scofield, Douglas G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Starri, Heiðmarsson
    Icelandic Institute of Natural History, Borgir Nordurslod, Iceland.
    Andersson, Martin G.I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Lindström, Eva S.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Johannesson, Hanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Sharing of photobionts in sympatric populations of Thamnolia and Cetraria lichens: evidence from high-throughput sequencing2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4406Article in journal (Refereed)
    Abstract [en]

    In this study, we explored the diversity of green algal symbionts (photobionts) in sympatric populations of the cosmopolitan lichen-forming fungi Thamnolia and Cetraria. We sequenced with both Sanger and Ion Torrent High-Throughput Sequencing technologies the photobiont ITS-region of 30 lichen thalli from two islands: Iceland and Öland. While Sanger recovered just one photobiont genotype from each thallus, the Ion Torrent data recovered 10–18 OTUs for each pool of 5 lichen thalli, suggesting that individual lichens can contain heterogeneous photobiont populations. Both methods showed evidence for photobiont sharing between Thamnolia and Cetraria on Iceland. In contrast, our data suggest that on Öland the two mycobionts associate with distinct photobiont communities, with few shared OTUs revealed by Ion Torrent sequencing. Furthermore, by comparing our sequences with public data, we identified closely related photobionts from geographically distant localities. Taken together, we suggest that the photobiont composition in Thamnolia and Cetraria results from both photobiont-mycobiont codispersal and local acquisition during mycobiont establishment and/or lichen growth. We hypothesize that this is a successful strategy for lichens to be flexible in the use of the most adapted photobiont for the environment.

  • 319.
    Orton, F.
    et al.
    Univ West Scotland, Sch Sci & Sport, Paisley, Renfrew, Scotland.
    Säfholm, Moa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Jansson, Erika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Carlsson, Ylva
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Eriksson, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Fick, J.
    Umea Univ, Dept Chem, Umea, Sweden.
    Webster, T. Uren
    Swansea Univ, Swansea, W Glam, Wales.
    McMillan, T.
    Univ West Scotland, Sch Sci & Sport, Paisley, Renfrew, Scotland.
    Leishman, M.
    Univ West Scotland, Sch Sci & Sport, Paisley, Renfrew, Scotland.
    Verbruggen, B.
    Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England.
    Economou, T.
    Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England.
    Tyler, C. R.
    Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England.
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Exposure to an anti-androgenic herbicide negatively impacts reproductive physiology and fertility in Xenopustropicalis2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9124Article in journal (Refereed)
    Abstract [en]

    Amphibians are threatened on a global scale and pollutants may be contributing to population declines, but how chemicals impact on their reproduction is poorly understood. We conducted a life cycle analysis to investigate the impacts of early life exposure to two anti-androgens (exposure until completion of metamorphosis; stage 66): flutamide, (50 mu g/L)/linuron (9 and 45 mu g/L)) on sexual development and breeding competence in Xenopus tropicalis. Our analyses included: mRNA levels of dmrt1, cyp17, amh, cyp19, foxl2 and ar (tadpoles/metamorphs), gonadal histomorphology (metamorphs/adults), mRNA levels of ar/gr (adult male brain/gonad/forelimb), testosterone/corticosterone levels (adult males), secondary sexual characteristics (forelimb width/nuptial pad: adult males) and breeding competence (amplexus/fertility: adult males). Compared to controls, feminised sex ratios and increased number of spermatogonia (adults) were observed after exposure to flutamide and the lower linuron concentration. Exposure to the lower linuron concentration also resulted in demasculinisation of secondary sexual characteristics and reduced male fertility. Flutamide exposure resulted in masculinisation of the nuptial pad and elevated mRNA levels of dmrt1, cyp17, amh and foxl2 in brains (metamorphs). Testosterone levels were higher in all treatment groups, however, overall few effects were observed in response to the higher linuron concentration. Our findings advance understanding of reproductive biology of X. tropicalis and illustrate negative effects of linuron on reproductive processes at a concentration measured in freshwater environments.

  • 320.
    Osterwalder, Stefan
    et al.
    Univ Basel, Dept Environm Sci, CH-4056 Basel, Switzerland;Swedish Univ Agr Sci, Dept Forest Ecol & Management, S-90183 Umea, Sweden.
    Bishop, Kevin
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL. Swedish Univ Agr Sci, Dept Aquat Sci & Assessment, S-75236 Uppsala, Sweden.
    Alewell, Christine
    Univ Basel, Dept Environm Sci, CH-4056 Basel, Switzerland.
    Fritsche, Johannes
    Univ Basel, Dept Environm Sci, CH-4056 Basel, Switzerland.
    Laudon, Hjalmar
    Swedish Univ Agr Sci, Dept Forest Ecol & Management, S-90183 Umea, Sweden.
    Akerblom, Staffan
    Swedish Univ Agr Sci, Dept Aquat Sci & Assessment, S-75236 Uppsala, Sweden.
    Nilsson, Mats B.
    Swedish Univ Agr Sci, Dept Forest Ecol & Management, S-90183 Umea, Sweden.
    Mercury evasion from a boreal peatland shortens the timeline for recovery from legacy pollution2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 16022Article in journal (Refereed)
    Abstract [en]

    Peatlands are a major source of methylmercury that contaminates downstream aquatic food webs. The large store of mercury (Hg) in peatlands could be a source of Hg for over a century even if deposition is dramatically reduced. However, the reliability of Hg mass balances can be questioned due to missing long-term land-atmosphere flux measurements. We used a novel micrometeorological system for continuous measurement of Hg peatland-atmosphere exchange to derive the first annual Hg budget for a peatland. The evasion of Hg (9.4 mu g m(-2) yr(-1)) over the course of a year was seven times greater than stream Hg export, and over two times greater than wet bulk deposition to the boreal peatland. Measurements of dissolved gaseous Hg in the peat pore water also indicate Hg evasion. The net efflux may result from recent declines in atmospheric Hg concentrations that have turned the peatland from a net sink into a source of atmospheric Hg. This net Hg loss suggests that open boreal peatlands and downstream ecosystems can recover more rapidly from past atmospheric Hg deposition than previously assumed. This has important implications for future levels of methylmercury in boreal freshwater fish and the estimation of historical Hg accumulation rates from peat profiles.

  • 321.
    Ozaki, N.
    et al.
    Osaka Univ, Grad Sch Engn, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.;Osaka Univ, Photon Pioneers Ctr, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan..
    Nellis, W. J.
    Harvard Univ, Dept Phys, Cambridge, MA 02138 USA..
    Mashimo, T.
    Kumamoto Univ, Shock Wave & Condensed Matter Res Ctr, Kumamoto 8608555, Japan..
    Ramzan, Muhammad
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. KTH Royal Inst Technol, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden..
    Kaewmaraya, Thanayut
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Kimura, T.
    Ehime Univ, Geodynam Res Ctr, Matsuyama, Ehime 7908577, Japan..
    Knudson, M.
    Sandia Natl Labs, POB 5800, Albuquerque, NM 87185 USA.;Washington State Univ, Inst Shock Phys, Pullman, WA 99164 USA..
    Miyanishi, K.
    Osaka Univ, Photon Pioneers Ctr, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan..
    Sakawa, Y.
    Osaka Univ, Inst Laser Engn, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan..
    Sano, T.
    Osaka Univ, Inst Laser Engn, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan..
    Kodama, R.
    Osaka Univ, Grad Sch Engn, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.;Osaka Univ, Photon Pioneers Ctr, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.;Osaka Univ, Inst Acad Initiat, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan..
    Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 26000Article in journal (Refereed)
    Abstract [en]

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gcl(3)Ga(5)O(12) (GGG), were measured at extremely high pressures up to 2.6TPa (26 Mbar) generated by high-power laser irradiation and magnetically driven hypervelocity impacts. Above 0.75TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions.

  • 322.
    Padhan, Narendra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Yan, Junhong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden.;Eindhoven Univ Technol, Inst Complex Mol Syst, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands..
    Boge, Annegret
    Protein Simple, 3001 Orchard Pkwy, San Jose, CA 95134 USA..
    Scrivener, Elaine
    Protein Simple, 3001 Orchard Pkwy, San Jose, CA 95134 USA..
    Birgisson, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Zieba, Agata
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Gullberg, Mats
    Olink Biosci, Dag Hammarskjolds Vag 52B, S-75237 Uppsala, Sweden..
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Rudbeck Lab, S-75185 Uppsala, Sweden..
    Highly sensitive and specific protein detection via combined capillary isoelectric focusing and proximity ligation2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1490Article in journal (Refereed)
    Abstract [en]

    Detection and quantification of proteins and their post-translational modifications are crucial to decipher functions of complex protein networks in cell biology and medicine. Capillary isoelectric focusing together with antibody-based detection can resolve and identify proteins and their isoforms with modest sample input. However, insufficient sensitivity prevents detection of proteins present at low concentrations and antibody cross-reactivity results in unspecific detection that cannot be distinguished from bona fide protein isoforms. By using DNA-conjugated antibodies enhanced signals can be obtained via rolling circle amplification (RCA). Both sensitivity and specificity can be greatly improved in assays dependent on target recognition by pairs of antibodies using in situ proximity ligation assays (PLA). Here we applied these DNA-assisted RCA techniques in capillary isoelectric focusing to resolve endogenous signaling transducers and isoforms along vascular endothelial growth factor (VEGF) signaling pathways at concentrations too low to be detected in standard assays. We also demonstrate background rejection and enhanced specificity when protein detection depended on binding by pairs of antibodies using in situ PLA, compared to assays where each antibody preparation was used on its own.

  • 323.
    Palm, Anna-Karin E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Friedrich, Heike C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Kleinau, Sandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Nodal marginal zone B cells in mice: a novel subset with dormant self-reactivity2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 27687Article in journal (Refereed)
    Abstract [en]

    Marginal zone (MZ) B cells, representing a distinct subset of innate-like B cells, mount rapid T-independent responses to blood-borne antigens. They express low-affinity polyreactive antigen receptors that recognize both foreign and self-structures. The spleen is considered the exclusive site for murine MZ B cells. However, we have here identified B cells with a MZ B-cell phenotype in the subcapsular sinuses of mouse lymph nodes. The nodal MZ (nMZ) B cells display high levels of IgM, costimulators and TLRs, and are represented by naive and memory cells. The frequency of nMZ B cells is about 1-6% of nodal B cells depending on mouse strain, with higher numbers in older mice and a trend of increased numbers in females. There is a significant expansion of nMZ B cells following immunization with an autoantigen, but not after likewise immunization with a control protein or with the adjuvant alone. The nMZ B cells secrete autoantibodies upon activation and can efficiently present autoantigen to cognate T cells in vitro, inducing T-cell proliferation. The existence of self-reactive MZ B cells in lymph nodes may be a source of autoantigen-presenting cells that in an unfortunate environment may activate T cells leading to autoimmunity.

  • 324.
    Palm, Anna-Karin E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Garcia-Faroldi, Gianni
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Lundberg, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden..
    Kleinau, Sandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Activated mast cells promote differentiation of B cells into effector cells2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20531Article in journal (Refereed)
    Abstract [en]

    Based on the known accumulation of mast cells (MCs) in B cell-dependent inflammatory diseases, including rheumatoid arthritis, we hypothesized that MCs directly modulate B cells. We show here that degranulated, and to a lesser extent naive or IgE-sensitized, MCs activate both naive and B cell receptor-activated B cells. This was shown by increased proliferation, blast formation, and expression of CD19, MHC class II and CD86 in the B cells. Further, MCs stimulated the secretion of IgM and IgG in IgM(+) B cells, indicating that MCs can induce class-switch recombination in B cells. We also show that coculture of MCs with B cells promotes surface expression of L-selectin, a homing receptor, on the B cells. The effects of MCs on B cells were partly dependent on cell-cell contact and both follicular and marginal zone B cells could be activated by MCs. Our findings suggest that degranulated MCs support optimal activation of B cells, a finding that is in line with in vivo studies showing that MCs frequently degranulate in the context of B-cell driven pathologies such as arthritis. Together, our findings show that MCs have the capacity to differentiate B cells to effector cells.

  • 325. Pappas, S. D.
    et al.
    Poulopoulos, P.
    Lewitz, B.
    Straub, A.
    Goschew, A.
    Kapaklis, Vassilios
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Wilhelm, F.
    Rogalev, A.
    Fumagalli, P.
    Direct evidence for significant spin-polarization of EuS in Co/EuS multilayers at room temperature2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 1333-Article in journal (Refereed)
    Abstract [en]

    The new era of spintronics promises the development of nanodevices, where the electron spin will be used to store information and charge currents will be replaced by spin currents. For this, ferromagnetic semiconductors at room temperature are needed. We report on significant room-temperature spin polarization of EuS in Co/EuS multilayers recorded by x-ray magnetic circular dichroism (XMCD). The films were found to contain a mixture of divalent and trivalent europium, but only Eu++ is responsible for the ferromagnetic behavior of EuS. The magnetic XMCD signal of Eu at room temperature could unambiguously be assigned to magnetic ordering of EuS and was found to be only one order of magnitude smaller than that at 2.5 K. The room temperature magnetic moment of EuS is as large as the one of bulk ferromagnetic Ni. Our findings pave the path for fabrication of room-temperature spintronic devices using spin polarized EuS layers.

  • 326.
    Parhizgar, Fariborz
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. IPM, Inst Res Fundamental Sci, Sch Phys, Tehran 193955531, Iran..
    Black-Schaffer, Annica M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Highly tunable time-reversal-invariant topological superconductivity in topological insulator thin films2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9817Article in journal (Refereed)
    Abstract [en]

    We study time-reversal-invariant topological superconductivity in topological insulator (TI) thin films including both intra-and inter-surface pairing. We find a nontrivial topology for multiple different configurations. For intra-surface pairing a p-phase difference between the intra-surface pairing states is required. We show that in this case the resulting topological phase is highly tunable by both an applied electric field and varied chemical potential. For spin-singlet inter-surface pairing, a sign-changing tunnel coupling present in many TI thin films is needed, and again, the topology can be tuned by electric field or doping. Notably, we find that the required inter-surface pairing strength for achieving nontrivial topology can still be subdominant compared to the intra-surface pairing. Finally, for spin-triplet intersurface pairing we prove that the superconducting state is always topological nontrivial. We show that thin films of Cu-doped Bi2Se3 will likely host such spin-triplet inter-surface pairing. Taken together, these results show that time-reversal-invariant topological superconductivity is common in superconducting TI thin films and that the topological phase and its Kramers pair of Majorana edge modes is highly tunable with an applied electric field and varied chemical potential.

  • 327.
    Park, Wook Ha
    et al.
    Kyung Hee Univ, Dept Physiol, Coll Med, Seoul 02447, South Korea..
    Kang, Sora
    Kyung Hee Univ, Dept Physiol, Coll Med, Seoul 02447, South Korea..
    Lee, Hong Kyu
    Eulji Univ, Dept Internal Med, Coll Med, Seoul 01830, South Korea..
    Salihovic, Samira
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden..
    van Bavel, Bert
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden..
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Pak, Youngmi Kim
    Kyung Hee Univ, Dept Physiol, Coll Med, Seoul 02447, South Korea..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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.

  • 328.
    Patra, Hirak K.
    et al.
    Linkoping Univ, IFM, Biosensors & Bioelect Ctr, S-58183 Linkoping, Sweden.;Linkoping Univ, Integrat Regenerat Med Ctr, S-58185 Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med IKE, Div Cell Biol, S-58185 Linkoping, Sweden..
    Imani, Roghayeh
    Linkoping Univ, IFM, Biosensors & Bioelect Ctr, S-58183 Linkoping, Sweden.;Univ Ljubljana, Fac Elect Engn, Biophys Lab, SI-1000 Ljubljana, Slovenia.;Univ Ljubljana, Fac Hlth Sci, Lab Clin Biophys, SI-1000 Ljubljana, Slovenia..
    Jangamreddy, Jaganmohan R.
    Linkoping Univ, Dept Clin & Expt Med IKE, Div Cell Biol, S-58185 Linkoping, Sweden..
    Pazoki, Meysam
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Iglic, Ales
    Univ Ljubljana, Fac Elect Engn, Biophys Lab, SI-1000 Ljubljana, Slovenia..
    Turner, Anthony P. F.
    Linkoping Univ, IFM, Biosensors & Bioelect Ctr, S-58183 Linkoping, Sweden..
    Tiwari, Ashutosh
    Linkoping Univ, IFM, Biosensors & Bioelect Ctr, S-58183 Linkoping, Sweden.;Tekidag AB, SE-58330 Linkoping, Sweden..
    On/off-switchable anti-neoplastic nanoarchitecture2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 14571Article in journal (Refereed)
    Abstract [en]

    Throughout the world, there are increasing demands for alternate approaches to advanced cancer therapeutics. Numerous potentially chemotherapeutic compounds are developed every year for clinical trial and some of them are considered as potential drug candidates. Nanotechnology-based approaches have accelerated the discovery process, but the key challenge still remains to develop therapeutically viable and physiologically safe materials suitable for cancer therapy. Here, we report a high turnover, on/off-switchable functionally popping reactive oxygen species (ROS) generator using a smart mesoporous titanium dioxide popcorn (TiO2 Pops) nanoarchitecture. The resulting TiO2 Pops, unlike TiO2 nanoparticles (TiO2 NPs), are exceptionally biocompatible with normal cells. Under identical conditions, TiO2 Pops show very high photocatalytic activity compared to TiO2 NPs. Upon on/off-switchable photo activation, the TiO2 Pops can trigger the generation of high-turnover flash ROS and can deliver their potential anticancer effect by enhancing the intracellular ROS level until it crosses the threshold to open the 'death gate', thus reducing the survival of cancer cells by at least six times in comparison with TiO2 NPs without affecting the normal cells.

  • 329.
    Paula, Jose Ricardo
    et al.
    Univ Lisbon, MARE Marine & Environm Sci Ctr, Lab Maritimo da Guia, Fac Ciencias, Av Nossa Senhora do Cabo 939, P-2750374 Cascais, Portugal.
    Repolho, Tiago
    Univ Lisbon, MARE Marine & Environm Sci Ctr, Lab Maritimo da Guia, Fac Ciencias, Av Nossa Senhora do Cabo 939, P-2750374 Cascais, Portugal.
    Pegado, Maria Rita
    Univ Lisbon, MARE Marine & Environm Sci Ctr, Lab Maritimo da Guia, Fac Ciencias, Av Nossa Senhora do Cabo 939, P-2750374 Cascais, Portugal.
    Thörnqvist, Per-Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Winberg: Behavioral Neuroendocrinology.
    Bispo, Regina
    Univ Nova Lisboa, Dept Matemat, Ctr Matemat & Aplicacoes, Fac Ciencias & Tecnol, Campus Caparica, P-2829516 Caparica, Portugal.
    Winberg, Svante
    Univ Lisbon, MARE Marine & Environm Sci Ctr, Lab Maritimo da Guia, Fac Ciencias, Av Nossa Senhora do Cabo 939, P-2750374 Cascais, Portugal.
    Munday, Philip L.
    James Cook Univ, ARC Ctr Excellence Coral Reef Studies, Townsville, Qld 4811, Australia.
    Rosa, Rui
    Univ Lisbon, MARE Marine & Environm Sci Ctr, Lab Maritimo da Guia, Fac Ciencias, Av Nossa Senhora do Cabo 939, P-2750374 Cascais, Portugal.
    Neurobiological and behavioural responses of cleaning mutualisms to ocean warming and acidification2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12728Article in journal (Refereed)
    Abstract [en]

    Cleaning interactions are textbook examples of mutualisms. On coral reefs, most fishes engage in cooperative interactions with cleaners fishes, where they benefit from ectoparasite reduction and ultimately stress relief. Furthermore, such interactions elicit beneficial effects on clients' ecophysiology. However, the potential effects of future ocean warming (OW) and acidification (OA) on these charismatic associations are unknown. Here we show that a 45-day acclimation period to OW (+3 degrees C) and OA (980 mu atm pCO(2)) decreased interactions between cleaner wrasses (Labroides dimidiatus) and clients (Naso elegans). Cleaners also invested more in the interactions by providing tactile stimulation under OA. Although this form of investment is typically used by cleaners to prolong interactions and reconcile after cheating, interaction time and client jolt rate (a correlate of dishonesty) were not affected by any stressor. In both partners, the dopaminergic (in all brain regions) and serotoninergic (forebrain) systems were significantly altered by these stressors. On the other hand, in cleaners, the interaction with warming ameliorated dopaminergic and serotonergic responses to OA. Dopamine and serotonin correlated positively with motivation to interact and cleaners interaction investment (tactile stimulation). We advocate that such neurobiological changes associated with cleaning behaviour may affect the maintenance of community structures on coral reefs.

  • 330.
    Pavliuk, Mariia V.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Fernandes, Arthur B.
    Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo, Brazil.
    Abdellah, Mohamed
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström. South Valley Univ, Qena Fac Sci, Dept Chem, Qena 83523, Egypt.
    Fernandes, Daniel L. A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Machado, Caroline O.
    Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo, Brazil.
    Rocha, Igor
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hattori, Yocefu
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Paun, Cristina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström.
    Bastos, Erick L.
    Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo, Brazil.
    Sá, Jacinto
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. Polish Acad Sci, Inst Phys Chem, PL-01224 Warsaw, Poland.
    Nano-hybrid plasmonic photocatalyst for hydrogen production at 20% efficiency2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 8670Article in journal (Refereed)
    Abstract [en]

    The efficient conversion of light energy into chemical energy is key for sustainable human development. Several photocatalytic systems based on photovoltaic electrolysis have been used to produce hydrogen via water reduction. However, in such devices, light harvesting and proton reduction are carried separately, showing quantum efficiency of about 10–12%. Here, we report a nano-hybrid photocatalytic assembly that enables concomitant reductive hydrogen production and pollutant oxidation with solar-to-fuel efficiencies up to 20%. The modular architecture of this plasmonic material allows the fine-tuning of its photocatalytic properties by simple manipulation of a reduced number of basic components.

  • 331.
    Pavlou, Andrea
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Jacques, Julien
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Ahmadova, Nigar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Mamedov, Fikret
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Styring, Stenbjörn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    The wavelength of the incident light determines the primary charge separation pathway in Photosystem II2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 2837Article in journal (Refereed)
    Abstract [en]

    Charge separation is a key component of the reactions cascade of photosynthesis, by which solar energy is converted to chemical energy. From this photochemical reaction, two radicals of opposite charge are formed, a highly reducing anion and a highly oxidising cation. We have previously proposed that the cation after far-red light excitation is located on a component different from P-D1, which is the location of the primary electron hole after visible light excitation. Here, we attempt to provide further insight into the location of the primary charge separation upon far-red light excitation of PS II, using the EPR signal of the spin polarized P-3(680) as a probe. We demonstrate that, under far-red light illumination, the spin polarized P-3(680) is not formed, despite the primary charge separation still occurring at these conditions. We propose that this is because under far-red light excitation, the primary electron hole is localized on Chl(D1), rather than on P-D1. The fact that identical samples have demonstrated charge separation upon both far-red and visible light excitation supports our hypothesis that two pathways for primary charge separation exist in parallel in PS II reaction centres. These pathways are excited and activated dependent of the wavelength applied.

  • 332.
    Peolsson, Anneli
    et al.
    Linkoping Univ, Div Physiotherapy, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden..
    Peterson, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Linkoping Univ, Div Physiotherapy, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden.
    Trygg, Johan
    Umea Univ, Computat Life Sci Cluster CLiC, Dept Chem, S-90187 Umea, Sweden..
    Nilsson, David
    Umea Univ, Computat Life Sci Cluster CLiC, Dept Chem, S-90187 Umea, Sweden..
    Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 30415Article in journal (Refereed)
    Abstract [en]

    Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD.

  • 333.
    Pervishko, Anastasiia A.
    et al.
    ITMO Univ, St Petersburg 197101, Russia.
    Baglai, Mikhail I.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. ITMO Univ, St Petersburg 197101, Russia.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Orebro Univ, Sch Sci & Technol, SE-70182 Orebro, Sweden.
    Yudin, Dmitry
    ITMO Univ, St Petersburg 197101, 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.

  • 334.
    Peters, Lars
    et al.
    Radboud Univ Nijmegen, Inst Mol & Mat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands..
    Ghosh, Saurabh
    Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA..
    Sanyal, Biplab
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    van Dijk, Chris
    Univ Amsterdam, Vant Hoff Inst Mol Sci, Sci Pk 904, NL-1098 XH Amsterdam, Netherlands..
    Bowlan, John
    Max Planck Gesell, Fritz Haber Inst, Faradayweg 4-6, D-14195 Berlin, Germany..
    de Heer, Walt
    Georgia Inst Technol, Sch Phys, 837 State Str, Atlanta, GA 30332 USA..
    Delin, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol KTH, Sch Informat & Commun Technol, Dept Mat & Nanophys, Electrum 229, SE-16440 Kista, Sweden.;KTH, SeRC, SE-10044 Stockholm, Sweden..
    Di Marco, Igor
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Eriksson, Olle
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Katsnelson, Mikhail I.
    Radboud Univ Nijmegen, Inst Mol & Mat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands.;Ural Fed Univ, Dept Theoret Phys & Appl Math, Ekaterinburg 620002, Russia..
    Johansson, Börje
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Kirilyuk, Andrei
    Radboud Univ Nijmegen, Inst Mol & Mat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands..
    Magnetism and exchange interaction of small rare-earth clusters: Tb as a representative2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 19676Article in journal (Refereed)
    Abstract [en]

    Here we follow, both experimentally and theoretically, the development of magnetism in Tb clusters from the atomic limit, adding one atom at a time. The exchange interaction is, surprisingly, observed to drastically increase compared to that of bulk, and to exhibit irregular oscillations as a function of the interatomic distance. From electronic structure theory we find that the theoretical magnetic moments oscillate with cluster size in exact agreement with experimental data. Unlike the bulk, the oscillation is not caused by the RKKY mechanism. Instead, the inter-atomic exchange is shown to be driven by a competition between wave-function overlap of the 5d shell and the on-site exchange interaction, which leads to a competition between ferromagnetic double-exchange and antiferromagnetic super-exchange. This understanding opens up new ways to tune the magnetic properties of rare-earth based magnets with nano-sized building blocks.

  • 335.
    Peterson, Gunnel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden..
    Nilsson, David
    Umea Univ, Computat Life Sci Cluster CLiC, Dept Chem, S-90187 Umea, Sweden..
    Trygg, Johan
    Umea Univ, Computat Life Sci Cluster CLiC, Dept Chem, S-90187 Umea, Sweden..
    Falla, Deborah
    Univ Gottingen, Inst Neurorehabil Syst, Bernstein Focus Neurotechnol BFNT Gottingen, Bernstein Ctr Computat Neurosci,Univ Med Ctr Gott, D-37073 Gottingen, Germany.;Univ Hosp Gottingen, Pain Clin, Ctr Anesthesiol Emergency & Intens Care Med, Gottingen, Germany..
    Dedering, Asa
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Physiotherapy, S-10401 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Phys Therapy, Solna, Sweden..
    Wallman, Thorne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Peolsson, Anneli
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden..
    Novel insights into the interplay between ventral neck muscles in individuals with whiplash-associated disorders2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15289Article in journal (Refereed)
    Abstract [en]

    Chronic whiplash-associated disorder (WAD) is common after whiplash injury, with considerable personal, social, and economic burden. Despite decades of research, factors responsible for continuing pain and disability are largely unknown, and diagnostic tools are lacking. Here, we report a novel model of mechanical ventral neck muscle function recorded from non-invasive, real-time, ultrasound measurements. We calculated the deformation area and deformation rate in 23 individuals with persistent WAD and compared them to 23 sex-and age-matched controls. Multivariate statistics were used to analyse interactions between ventral neck muscles, revealing different interplay between muscles in individuals with WAD and healthy controls. Although the cause and effect relation cannot be established from this data, for the first time, we reveal a novel method capable of detecting different neck muscle interplay in people with WAD. This non-invasive method stands to make a major breakthrough in the assessment and diagnosis of people following a whiplash trauma.

  • 336.
    Peterson, Gunnel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden.
    Nilsson, David
    Umea Univ, Dept Chem, Computat Life Sci Cluster CLiC, Umea, Sweden.
    Trygg, Johan
    Umea Univ, Dept Chem, Computat Life Sci Cluster CLiC, Umea, Sweden.
    Peolsson, Anneli
    Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden.
    Neck-specific exercise improves impaired interactions between ventral neck muscles in chronic whiplash: A randomized controlled ultrasound study2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 9649Article in journal (Refereed)
    Abstract [en]

    Chronic pain and disability is common in whiplash-associated disorders (WAD), leading to personal suffering, sick leave, and social cost. The cervical spine is heavily dependent on muscular support and whiplash injury can cause damage to the neck muscles, but diagnostic tools to measure neck muscle impairment and evaluate exercise interventions are lacking. Therefore, the present study investigated ventral neck muscle interactions in 26 individuals with chronic WAD randomized to neck-specific exercise (NSE) or remaining on a waiting list (WL) in 3 months. We performed real-time, non-invasive ultrasound measurements with speckle tracking analysis and calculated the deformation area and deformation rate in three ventral neck muscles. Multivariate statistics were used to analyse interactions between the muscles. After 3 months of NSE, significant improvements were observed in neck muscle interactions and pain intensity in the NSE group compared to the WL group. Thus, this study demonstrates that non-invasive ultrasound can be a diagnostic tool for muscle impairment and used to evaluate exercise interventions in WAD and stands to make a breakthrough for better management in chronic WAD.

  • 337.
    Pettersson, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Zarnegar, Behdad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Westin, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Persson, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Peuckert, Christiane
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Jonsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hallgren, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    SLC10A4 regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1085Article in journal (Refereed)
    Abstract [en]

    Mast cells act as sensors in innate immunity and as effector cells in adaptive immune reactions. Here we demonstrate that SLC10A4, also referred to as the vesicular aminergic-associated transporter, VAAT, modifies mast cell degranulation. Strikingly, Slc10a4(-/-) bone marrow-derived mast cells (BMMCs) had a significant reduction in the release of granule-associated mediators in response to IgE/antigen-mediated activation, whereas the in vitro development of mast cells, the storage of the granule-associated enzyme mouse mast cell protease 6 (mMCP-6), and the release of prostaglandin D2 and IL-6 were normal. Slc10a4-deficient mice had a strongly reduced passive cutaneous anaphylaxis reaction and a less intense itching behaviour in response to the mast cell degranulator 48/80. Live imaging of the IgE/antigen-mediated activation showed decreased degranulation and that ATP was retained to a higher degree in mast cell granules lacking SLC10A4. Furthermore, ATP was reduced by two thirds in Slc10a4(-/-) BMMCs supernatants in response to IgE/antigen. We speculate that SLC10A4 affects the amount of granule-associated ATP upon IgE/antigen-induced mast cell activation, which affect the release of granule-associated mast cell mediators. In summary, SLC10A4 acts as a regulator of degranulation in vitro and of mast cell-related reactions in vivo.

  • 338.
    Pettersson, John
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Sydney, Sch Life & Environm Sci, Charles Perkins Ctr, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.;Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.;Norwegian Inst Publ Hlth, Infect Dis Control & Environm Hlth, Oslo, Norway.;Natl Vet Inst, Dept Microbiol, Uppsala, Sweden.
    Shi, Mang
    Univ Sydney, Sch Life & Environm Sci, Charles Perkins Ctr, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.;Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia..
    Bohlin, Jon
    Norwegian Inst Publ Hlth, Infect Dis Control & Environm Hlth, Oslo, Norway..
    Eldholm, Vegard
    Norwegian Inst Publ Hlth, Infect Dis Control & Environm Hlth, Oslo, Norway..
    Brynildsrud, Ola B.
    Norwegian Inst Publ Hlth, Infect Dis Control & Environm Hlth, Oslo, Norway..
    Paulsen, Katrine Mork
    Norwegian Inst Publ Hlth, Infect Dis Control & Environm Hlth, Oslo, Norway.;Norwegian Univ Life Sci, Fac Vet Med, Dept Prod Anim Clin Sci, Oslo, Norway..
    Andreassen, Ashild
    Norwegian Inst Publ Hlth, Infect Dis Control & Environm Hlth, Oslo, Norway..
    Holmes, Edward C.
    Univ Sydney, Sch Life & Environm Sci, Charles Perkins Ctr, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.;Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia..
    Characterizing the virome of Ixodes ricinus ticks from northern Europe2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10870Article in journal (Refereed)
    Abstract [en]

    RNA viruses are abundant infectious agents and present in all domains of life. Arthropods, including ticks, are well known as vectors of many viruses of concern for human and animal health. Despite their obvious importance, the extent and structure of viral diversity in ticks is still poorly understood, particularly in Europe. Using a bulk RNA-sequencing approach that captures the complete transcriptome, we analysed the virome of the most common tick in Europe - Ixodes ricinus. In total, RNA sequencing was performed on six libraries consisting of 33 I. ricinus nymphs and adults sampled in Norway. Despite the small number of animals surveyed, our virus identification pipeline revealed nine diverse and novel viral species, phylogenetically positioned within four different viral groups bunyaviruses, luteoviruses, mononegavirales and partitiviruses - and sometimes characterized by extensive genetic diversity including a potentially novel genus of bunyaviruses. This work sheds new light on the virus diversity in I. ricinus, expands our knowledge of potential host/vector-associations and tick-transmitted viruses within several viral groups, and pushes the latitudinal limit where it is likely to find tick-associated viruses. Notably, our phylogenetic analysis revealed the presence of tick-specific virus clades that span multiple continents, highlighting the role of ticks as important virus reservoirs.

  • 339.
    Peura, Sari
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sinclair, Lucas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eiler, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Metagenomic insights into strategies of aerobic and anaerobic carbon and nitrogen transformation in boreal lakes2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 12102Article in journal (Refereed)
    Abstract [en]

    Thousands of net-heterotrophic and strongly stratifying lakes dominate the boreal landscape. Besides their central role as emitters of greenhouse gases, we have only recently begun to understand the microbial systems driving the metabolic processes and elemental cycles in these lakes. Using shotgun metagenomics, we show that the functional potential differs among lake types, with humic lakes being particularly enriched in carbon degradation genes. Most of the metabolic pathways exhibit oxygen- and temperature-dependent stratification over depth, coinciding with shifts in bacterial community composition, implying that stratification is a major factor controlling lake metabolism. In the bottom waters, rare and poorly characterized taxa, such as epsilon-Proteobacteria, but also autotrophs, such as photolithotrophic Chlorobia were abundant. These oxygen-depleted layers exhibited high genetic potential for mineralization, but also for fixation of carbon and nitrogen, and genetic markers for both methane production and oxidation were present. Our study provides a first glimpse of the genetic versatility of freshwater anoxic zones, and demonstrates the potential for complete turnover of carbon compounds within the water column.

  • 340.
    Pohl, Darius
    et al.
    IFW Dresden, Inst Metall Mat, Helmholtzstr 20, D-01069 Dresden, Germany..
    Schneider, Sebastian
    IFW Dresden, Inst Metall Mat, Helmholtzstr 20, D-01069 Dresden, Germany.;Tech Univ Dresden, Inst Solid State Phys, D-01062 Dresden, Germany..
    Zeiger, Paul
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Rusz, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Tiemeijer, Peter
    FEI Co, POB 80066, NL-5600 KA Eindhoven, Netherlands..
    Lazar, Sorin
    FEI Co, POB 80066, NL-5600 KA Eindhoven, Netherlands..
    Nielsch, Kornelius
    IFW Dresden, Inst Metall Mat, Helmholtzstr 20, D-01069 Dresden, Germany.;Tech Univ Dresden, Inst Werkstoffwissensch, D-01062 Dresden, Germany..
    Rellinghaus, Bernd
    IFW Dresden, Inst Metall Mat, Helmholtzstr 20, D-01069 Dresden, Germany..
    Atom size electron vortex beams with selectable orbital angular momentum2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 934Article in journal (Refereed)
    Abstract [en]

    The decreasing size of modern functional magnetic materials and devices cause a steadily increasing demand for high resolution quantitative magnetic characterization. Transmission electron microscopy (TEM) based measurements of the electron energy-loss magnetic chiral dichroism (EMCD) may serve as the needed experimental tool. To this end, we present a reliable and robust electron-optical setup that generates and controls user-selectable single state electron vortex beams with defined orbital angular momenta. Our set-up is based on a standard high-resolution scanning TEM with probe aberration corrector, to which we added a vortex generating fork aperture and a miniaturized aperture for vortex selection. We demonstrate that atom size probes can be formed from these electron vortices and that they can be used for atomic resolution structural and spectroscopic imaging - both of which are prerequisites for future atomic EMCD investigations.

  • 341. Popov, Leonid E
    et al.
    Alvaro, Javier J
    Holmer, Lars E.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology. Shaanxi Key laboratory of Early Life and Environments, State Key Laboratory of Continental Dynamics and Department of Geology, Northwest University, Xi’an, China.
    Bauert, Heikki
    Ghobadi Pour, Mansoureh
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology. Department of Geology, Faculty of Sciences, Golestan University, Gorgan, Iran; Department of Earth Sciences, National Museum of Wales, UK .
    Dronov, Andrei V
    Lehnert, Oliver
    Hints, Olle
    Männik, Peep
    Zhang, Zhifei
    Zhang, Zhiliang
    Glendonite occurrences in the Tremadocian of Baltica: first Early Palaeozoic evidence of massive ikaite precipitation at temperate latitude2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7205Article in journal (Refereed)
    Abstract [en]

    The Tremadocian (Early Ordovician) is currently considered a time span of greenhouse conditions with tropical water surface temperature estimates, interpolated from oxygen isotopes, approaching 40 °C. In the mid-latitude Baltoscandian Basin, conodonts displaying low δ18O values, which suggest high temperatures (>40 °C) in the water column, are in contrast with the discovery of contemporaneous glendonite clusters, a pseudomorph of ikaite (CaCO3·6H2O) traditionally considered as indicator of near-freezing bottom-water conditions. The massive precipitation of this temperature sensitive mineral is associated with transgressive conditions and high organic productivity. As a result, the lower Tremadocian sediments of Baltoscandia apparently contain both "greenhouse" pelagic signals and near-freezing substrate indicators. This paradox points to other primary controlling mechanisms for ikaite precipitation in kerogenous substrates, such as carbonate alkalinity, pH and Mg/Ca ratios, as recently constrained by laboratory experiments. Preservation of "hot" conodonts embedded in kerogenous shales rich in δ18O-depleted glendonites suggests both the onset of sharp thermal stratification patterns in a semi-closed basin and the assumed influence of isotopically depleted freshwater yielded by fluvial systems.

  • 342.
    Poropat, Stephen F.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences. Australian Age Dinosaurs Museum Nat Hist, Winton, Qld, Australia..
    Mannion, Philip D.
    Imperial Coll London, Dept Earth Sci & Engn, South Kensington Campus, London SW7 2AZ, England..
    Upchurch, Paul
    UCL, Dept Earth Sci, Gower St, London WC1E 6BT, England..
    Hocknull, Scott A.
    Queensland Museum, Geosci, Hendra, Qld, Australia..
    Kear, Benjamin P.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences. Uppsala University, Music and Museums, Museum of Evolution.
    Kundrat, Martin
    Comenius Univ, Dept Ecol, Fac Nat Sci, Ilkovicova 6, SK-84215 Bratislava, Slovakia.;Safarik Univ, Ctr Interdisciplinary Biosci, Fac Sci, Jesenna 5, SK-04154 Kosice, Slovakia..
    Tischler, Travis R.
    Australian Age Dinosaurs Museum Nat Hist, Winton, Qld, Australia..
    Sloan, Trish
    Australian Age Dinosaurs Museum Nat Hist, Winton, Qld, Australia..
    Sinapius, George H. K.
    Australian Age Dinosaurs Museum Nat Hist, Winton, Qld, Australia..
    Elliott, Judy A.
    Australian Age Dinosaurs Museum Nat Hist, Winton, Qld, Australia..
    Elliott, David A.
    Australian Age Dinosaurs Museum Nat Hist, Winton, Qld, Australia..
    New Australian sauropods shed light on Cretaceous dinosaur palaeobiogeography2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 34467Article in journal (Refereed)
    Abstract [en]

    Australian dinosaurs have played a rare but controversial role in the debate surrounding the effect of Gondwanan break-up on Cretaceous dinosaur distribution. Major spatiotemporal gaps in the Gondwanan Cretaceous fossil record, coupled with taxon incompleteness, have hindered research on this effect, especially in Australia. Here we report on two new sauropod specimens from the early Late Cretaceous of Queensland, Australia, that have important implications for Cretaceous dinosaur palaeobiogeography. Savannasaurus elliottorum gen. et sp. nov. comprises one of the most complete Cretaceous sauropod skeletons ever found in Australia, whereas a new specimen of Diamantinasaurus matildae includes the first ever cranial remains of an Australian sauropod. The results of a new phylogenetic analysis, in which both Savannasaurus and Diamantinasaurus are recovered within Titanosauria, were used as the basis for a quantitative palaeobiogeographical analysis of macronarian sauropods. Titanosaurs achieved a worldwide distribution by at least 125 million years ago, suggesting that mid-Cretaceous Australian sauropods represent remnants of clades which were widespread during the Early Cretaceous. These lineages would have entered Australasia via dispersal from South America, presumably across Antarctica. High latitude sauropod dispersal might have been facilitated by Albian-Turonian warming that lifted a palaeoclimatic dispersal barrier between Antarctica and South America.

  • 343.
    Porra, L.
    et al.
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Med Imaging Ctr, Helsinki, Finland..
    Degrugilliers, L.
    Amiens Univ Hosp, Dept Pediat Intens Care, Amiens, France..
    Broche, Ludovic
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Albu, G.
    Univ Hosp Geneva, Anesthesiol Invest Unit, Geneva, Switzerland..
    Strengell, S.
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Med Imaging Ctr, Helsinki, Finland..
    Suhonen, H.
    Univ Helsinki, Dept Phys, Helsinki, Finland..
    Fodor, G. H.
    Univ Hosp Geneva, Anesthesiol Invest Unit, Geneva, Switzerland..
    Petak, F.
    Univ Szeged, Dept Med Phys & Informat, Szeged, Hungary..
    Suortti, P.
    Univ Helsinki, Dept Phys, Helsinki, Finland..
    Habre, W.
    Univ Hosp Geneva, Anesthesiol Invest Unit, Geneva, Switzerland..
    Sovijärvi, A. R. A.
    Univ Helsinki, Cent Hosp, Dept Clin Physiol & Nucl Med, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland..
    Bayat, S.
    Univ Grenoble, EA 7442, RSRM Lab, Grenoble, France.;Grenoble Univ Hosp, Dept Clin Physiol Sleep & Exercise, Grenoble, France..
    Quantitative Imaging of Regional Aerosol Deposition, Lung Ventilation and Morphology by Synchrotron Radiation CT2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3519Article in journal (Refereed)
    Abstract [en]

    To understand the determinants of inhaled aerosol particle distribution and targeting in the lung, knowledge of regional deposition, lung morphology and regional ventilation, is crucial. No single imaging modality allows the acquisition of all such data together. Here we assessed the feasibility of dual-energy synchrotron radiation imaging to this end in anesthetized rabbits; both in normal lung (n = 6) and following methacholine (MCH)-induced bronchoconstriction (n = 6), a model of asthma. We used K-edge subtraction CT (KES) imaging to quantitatively map the regional deposition of iodine-containing aerosol particles. Morphological and regional ventilation images were obtained, followed by quantitative regional iodine deposition maps, after 5 and 10 minutes of aerosol administration. Iodine deposition was markedly inhomogeneous both in normal lung and after induced bronchoconstrition. Deposition was significantly reduced in the MCH group at both time points, with a strong dependency on inspiratory flow in both conditions (R-2 = 0.71; p < 0.0001). We demonstrate for the first time, the feasibility of KES CT for quantitative imaging of lung deposition of aerosol particles, regional ventilation and morphology. Since these are among the main factors determining lung aerosol deposition, we expect this imaging approach to bring new contributions to the understanding of lung aerosol delivery, targeting, and ultimately biological efficacy.

  • 344.
    Pour, Soudabeh Rad
    et al.
    Karolinska Inst, Ctr Mol Med, Dept Med, Unit Computat Med, SE-17176 Stockholm, Sweden.
    Morikawa, Hiromasa
    King Abdullah Univ Sci & Technol, Biol & Environm Sci & Engn Div BESE, Comp Elect & Math Sci & Engn Div CEMSE, Thuwal 239556900, Saudi Arabia.
    Kiani, Narsis A
    Karolinska Inst, Ctr Mol Med, Dept Med, Unit Computat Med, SE-17176 Stockholm, Sweden;Karolinska Inst, Algorithm Dynam Lab, Unit Computat Med, Dept Med Solna,Ctr Mol Med, SE-17177 Stockholm, Sweden;SciLifeLab, SE-17177 Stockholm, Sweden.
    Yang, Muyi
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
    Azimi, Alireza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Shafi, Gowhar
    Posit Biosci, Dept Genom & Bioinformat, Mumbai 400002, Maharashtra, India.
    Shang, Mingmei
    Karolinska Inst, Ctr Mol Med, Dept Med, Unit Computat Med, SE-17176 Stockholm, Sweden.
    Baumgartner, Roland
    Karolinska Univ Hosp, Expt Cardiovasc Res Grp, Cardiovasc Med Unit, Ctr Mol Med,Dept Med,Karolinska Inst, SE-17176 Stockholm, Sweden.
    Ketelhuth, Daniel F. J.
    Karolinska Univ Hosp, Expt Cardiovasc Res Grp, Cardiovasc Med Unit, Ctr Mol Med,Dept Med,Karolinska Inst, SE-17176 Stockholm, Sweden.
    Kamleh, Muhammad Anas
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, SE-17177 Stockholm, Sweden.
    Wheelock, Craig E.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 2, SE-17177 Stockholm, Sweden.
    Lundqvist, Andreas
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
    Hansson, Johan
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
    Tegnér, Jesper
    Karolinska Inst, Ctr Mol Med, Dept Med, Unit Computat Med, SE-17176 Stockholm, Sweden;King Abdullah Univ Sci & Technol, Biol & Environm Sci & Engn Div BESE, Comp Elect & Math Sci & Engn Div CEMSE, Thuwal 239556900, Saudi Arabia.
    Exhaustion of CD4+T-cells mediated by the Kynurenine Pathway in Melanoma2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12150Article in journal (Refereed)
    Abstract [en]

    Kynurenine pathway (KP) activation by the enzymatic activity of indoleamine 2,3-dioxygenase1 (IDO1) and kynurenine (KYN) production represents an attractive target for reducing tumour progression and improving anti-tumour immunity in multiple cancers. However, immunomodulatory properties of other KP metabolites such as 3-hydroxy kynurenine (3-HK) and kynurenic acid (KYNA) are poorly understood. The association of the kynurenine metabolic pathway with T-cell status in the tumour microenvironment were characterized, using gene expression data of 368 cutaneous skin melanoma (SKCM) patients from the TCGA cohort. Based on the identified correlations, we characterized the production of KYN, 3-HK, and KYNA in vitro using melanoma-derived cell lines and primary CD4+ CD25- T-cells. Activation of the CD4+ T-cells produced IFN gamma, which yielded increased levels of KYN and KYNA. Concurrently, kynurenine 3-monooxygenase (KMO) expression and proliferation of CD4+ T-cells were reduced, whereas exhaustion markers such as PD-L1, AHR, FOXP3, and CTLA4 were increased. Additionally, an analysis of the correlation network reconstructed using TCGA-SKCM emphasized KMO and KYNU with high variability among BRAF wild-type compared with V600E, which underscored their role in distinct CD4+ T-cell behavior in tumour immunity. Our results suggest that, in addition to IDO1, there is an alternative immune regulatory mechanism associated with the lower KMO expression and the higher KYNA production, which contributes to dysfunctional effector CD4+ T-cell response.

  • 345.
    Prasongkit, Jariyanee
    et al.
    Nakhon Phanom Univ, Div Phys, Fac Sci, Nakhon Phanom 48000, Thailand.;NanotecKKU Ctr Excellence Adv Nanomat Energy Prod, Khon Kaen 40002, Thailand..
    Feliciano, Gustavo T.
    Univ Estadual Paulista UNESP, Inst Chem, Dept Phys Chem, Araraquara, SP, Brazil..
    Rocha, Alexandre R.
    Univ Estadual Paulista UNESP, Inst Fis Teor, Sao Paulo, SP, Brazil..
    He, Yuhui
    Huazhong Univ Sci & Technol, Sch Opt & Elect Informat, Wuhan 430074, Peoples R China..
    Osotchan, Tanakorn
    Mahidol Univ, Dept Phys, Fac Sci, Bangkok 10400, Thailand..
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol, Dept Mat & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden..
    Scheicher, Ralph H.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Theoretical assessment of feasibility to sequence DNA through interlayer electronic tunneling transport at aligned nanopores in bilayer graphene2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 17560Article in journal (Refereed)
    Abstract [en]

    Fast, cost effective, single-shot DNA sequencing could be the prelude of a new era in genetics. As DNA encodes the information for the production of proteins in all known living beings on Earth, determining the nucleobase sequences is the first and necessary step in that direction. Graphene-based nanopore devices hold great promise for next-generation DNA sequencing. In this work, we develop a novel approach for sequencing DNA using bilayer graphene to read the interlayer conductance through the layers in the presence of target nucleobases. Classical molecular dynamics simulations of DNA translocation through the pore were performed to trace the nucleobase trajectories and evaluate the interaction between the nucleobases and the nanopore. This interaction stabilizes the bases in different orientations, resulting in smaller fluctuations of the nucleobases inside the pore. We assessed the performance of a bilayer graphene nanopore setup for the purpose of DNA sequencing by employing density functional theory and non-equilibrium Green's function method to investigate the interlayer conductance of nucleobases coupling simultaneously to the top and bottom graphene layers. The obtained conductance is significantly affected by the presence of DNA in the bilayer graphene nanopore, allowing us to analyze DNA sequences.

  • 346.
    Qvarnström, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Ahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Niedzwiedzki, Grzegorz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Tyrannosaurid-like osteophagy by a Triassic archosaur2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 925Article in journal (Refereed)
    Abstract [en]

    Here we present evidence for osteophagy in the Late Triassic archosaur Smok wawelski Niedzwiedzki, Sulej and Dzik, 2012, a large theropod-like predator from Poland. Ten medium to large-sized coprolites are matched, by their dimensions and by association with body fossils and footprints, to S. wawelski. The coprolites contain fragments of large serrated teeth as well as up to 50 percent by volume of bone fragments, with distinct fragmentation and angularity, from several prey taxa. This suggests pronounced osteophagy. Further evidence for bone-crushing behaviour is provided by isolated worn teeth, bone-rich regurgitalites (fossil regurgitates) and numerous examples of crushed or bite-marked dicynodont bones, all collected from the same bone-bearing beds in the Lipie Slaskie clay-pit. Several of the anatomical characters related to osteophagy, such as a massive head and robust body, seem to be shared by S. wawelski and the tyrannosaurids, despite their wide phylogenetic separation. These large predators thus provide evidence of convergence driven by similar feeding ecology at the beginning and end of the age of dinosaurs.

  • 347.
    Qvarnström, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Niedzwiedzki, Grzegorz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Tafforeau, Paul
    European Synchrotron Radiat Facil, 71 Ave Martyrs,CS40200, F-38043 Grenoble, France..
    Zigaite, Zivile
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Ahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Synchrotron phase-contrast microtomography of coprolites generates novel palaeobiological data2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2723Article in journal (Refereed)
    Abstract [en]

    Coprolites (fossil faeces) reveal clues to ancient trophic relations, and contain inclusions representing organisms that are rarely preserved elsewhere. However, much information is lost by classical techniques of investigation, which cannot find and image the inclusions in an adequate manner. We demonstrate that propagation phase-contrast synchrotron microtomography (PPC-SR mu CT) permits high-quality virtual 3D-reconstruction of coprolite inclusions, exemplified by two coprolites from the Upper Triassic locality Krasiejow, Poland; one of the coprolites contains delicate beetle remains, and the other one a partly articulated fish and fragments of bivalves.

  • 348.
    Qvarnström, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Szrek, Piotr
    Natl Res Inst, Polish Geol Inst, Rakowiecka 4 St, PL-00075 Warsaw, Poland..
    Ahlberg, Per E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Niedzwiedzki, Grzegorz
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Non-marine palaeoenvironment associated to the earliest tetrapod tracks2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1074Article in journal (Refereed)
    Abstract [en]

    Opinions differ on whether the evolution of tetrapods (limbed vertebrates) from lobe-finned fishes was directly linked to terrestrialization. The earliest known tetrapod fossils, from the Middle Devonian (approximately 390 million years old) of Zachelmie Quarry in Poland, are trackways made by limbs with digits; they document a direct environmental association and thus have the potential to help answer this question. However, the tetrapod identity of the tracks has recently been challenged, despite their well-preserved morphology, on account of their great age and supposedly shallow marine (intertidal or lagoonal) depositional environment. Here we present a new palaeoenvironmental interpretation of the track-bearing interval from Zachelmie, showing that it represents a succession of ephemeral lakes with a restricted and non-marine biota, rather than a marginal marine environment as originally thought. This context suggests that the trackmaker was capable of terrestrial locomotion, consistent with the appendage morphology recorded by the footprints, and thus provides additional support for a tetrapod identification.

  • 349.
    Reyhani, Vahid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tsioumpekou, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    van Wieringen, Tijs
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rask, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lennartsson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rubin, Kristofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 8924Article in journal (Refereed)
    Abstract [en]

    Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-β (PDGF-Rβ). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3'-kinase (PI3K) and phospholipase Cγ (PLCγ) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-Rβ were, however, dispensable. The decisive roles for PI3K and PLCγ were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLCγ down-stream of PDGF-Rβ. Moreover, inhibition of protein kinase C (PKC) by GÖ6976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4β-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLCγ-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction.

  • 350.
    Rinne, Sara S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Leitao, Charles Dahlsson
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Mitran, Bogdan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Bass, Tarek Z.
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Andersson, Ken G.
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Stahl, Stefan
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Lofblom, John
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
    Orlova, Anna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Optimization of HER3 expression imaging using affibody molecules: Influence of chelator for labeling with indium-1112019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 655Article in journal (Refereed)
    Abstract [en]

    Radionuclide molecular imaging of human epidermal growth factor receptor 3 (HER3) expression using affibody molecules could be used for patient stratification for HER3-targeted cancer therapeutics. We hypothesized that the properties of HER3-targeting affibody molecules might be improved through modification of the radiometal-chelator complex. Macrocyclic chelators NOTA (1,4,7-triazacyclononane-N,N',N ''-triacetic acid), NODAGA (1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid), and DOTAGA (1,4,7,10-tetraazacyclododececane, 1-(glutaric acid)-4,7,10-triacetic acid) were conjugated to the C-terminus of anti-HER3 affibody molecule Z(08698) and conjugates were labeled with indium-111. All conjugates bound specifically and with picomolar affinity to HER3 in vitro. In mice bearing HER3-expressing xenografts, no significant difference in tumor uptake between the conjugates was observed. Presence of the negatively charged In-111-DOTAGA-complex resulted in the lowest hepatic uptake and the highest tumor-to-liver ratio. In conclusion, the choice of chelator influences the biodistribution of indium-111 labeled anti-HER3 affibody molecules. Hepatic uptake of anti-HER3 affibody molecules could be reduced by the increase of negative charge of the radiometal-chelator complex on the C-terminus without significantly influencing the tumor uptake.

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