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  • 251.
    Lindh, E. Mattias
    et al.
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Lundberg, Petter
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Lanz, Thomas
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Mindemark, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry. Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Edman, Ludvig
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    The Weak Microcavity as an Enabler for Bright and Fault-tolerant Light-emitting Electrochemical Cells2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6970Article in journal (Refereed)
    Abstract [en]

    The light-emitting electrochemical cell (LEC) is functional at substantial active-layer thickness, and is as such heralded for being fit for low-cost and fault-tolerant solution-based fabrication. We report here that this statement should be moderated, and that in order to obtain a strong luminous output, it is fundamentally important to fabricate LEC devices with a designed thickness of the active layer. By systematic experimentation and simulation, we demonstrate that weak optical microcavity effects are prominent in a common LEC system, and that the luminance and efficiency, as well as the emission color and the angular intensity, vary in a periodic manner with the active-layer thickness. Importantly, we demonstrate that high-performance light-emission can be attained from LEC devices with a significant active-layer thickness of 300 nm, which implies that low-cost solution-processed LECs are indeed a realistic option, provided that the device structure has been appropriately designed from an optical perspective.

  • 252.
    Lindner, Philip
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Ctr Dependence Disorders, Stockholm, Sweden.;Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Flodin, Par
    Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden.;Umea Univ, Ctr Aging & Demog Res, Umea, Sweden..
    Larm, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Budhiraja, Meenal
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Savic-Berglund, Ivanka
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Neurol Clin, Huddinge, Sweden..
    Jokinen, Jussi
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Umea Univ, Dept Clin Sci, Umea, Sweden..
    Tiihonen, Jari
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland..
    Hodgins, Sheilagh
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Univ Montreal, Dept Psychiat, Montreal, PQ, Canada..
    Amygdala-orbitofrontal structural and functional connectivity in females with anxiety disorders, with and without a history of conduct disorder2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1101Article in journal (Refereed)
    Abstract [en]

    Conduct disorder (CD) and anxiety disorders (ADs) are often comorbid and both are characterized by hyper-sensitivity to threat, and reduced structural and functional connectivity between the amygdala and orbitofrontal cortex (OFC). Previous studies of CD have not taken account of ADs nor directly compared connectivity in the two disorders. We examined three groups of young women: 23 presenting CD and lifetime AD; 30 presenting lifetime AD and not CD; and 17 with neither disorder (ND). Participants completed clinical assessments and diffusion-weighted and resting-state functional MRI scans. The uncinate fasciculus was reconstructed using tractography and manual dissection, and structural measures extracted. Correlations of resting-state activity between amygdala and OFC seeds were computed. The CD + AD and AD groups showed similarly reduced structural integrity of the left uncinate compared to ND, even after adjusting for IQ, psychiatric comorbidity, and childhood maltreatment. Uncinate integrity was associated with harm avoidance traits among AD-only women, and with the interaction of poor anger control and anxiety symptoms among CD + AD women. Groups did not differ in functional connectivity. Reduced uncinate integrity observed in CD + AD and AD-only women may reflect deficient emotion regulation in response to threat, common to both disorders, while other neural mechanisms determine the behavioral response.

  • 253.
    Lindstrom, Ida
    et al.
    Stockholm Univ, Dept Biochem & Biophys.
    Andersson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dogan, Jakob
    Stockholm Univ, Dept Biochem & Biophys.
    The transition state structure for binding between TAZ1 of CBP and the disordered Hif-1 alpha CAD2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7872Article in journal (Refereed)
    Abstract [en]

    Intrinsically disordered proteins (IDPs) are common in eukaryotes. However, relatively few experimental studies have addressed the nature of the rate-limiting transition state for the coupled binding and folding reactions involving IDPs. By using site-directed mutagenesis in combination with kinetics measurements we have here characterized the transition state for binding between the globular TAZ1 domain of CREB binding protein and the intrinsically disordered C-terminal activation domain of Hif-1 alpha (Hif-1 alpha CAD). A total of 17 Hif-1 alpha CAD point-mutations were generated and a F-value binding analysis was carried out. We found that native hydrophobic binding interactions are not formed at the transition state. We also investigated the effect the biologically important Hif-1 alpha CAD Asn-803 hydroxylation has on the binding kinetics, and found that the whole destabilization effect due the hydroxylation is within the dissociation rate constant. Thus, the rate-limiting transition state is "disordered-like", with native hydrophobic binding contacts being formed cooperatively after the rate-limiting barrier, which is clearly shown by linear free energy relationships. The same behavior was observed in a previously characterized TAZ1/IDP interaction, which may suggest common features for the rate-limiting transition state for TAZ1/IDP interactions.

  • 254.
    Lindström, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Bergman, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Growth patterns during early childhood in children born small for gestational age and moderate preterm2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 11578Article in journal (Refereed)
    Abstract [en]

    Today we lack knowledge if size at birth and gestational age interacts regarding postnatal growth pattern in children born at 32 gestational weeks or later.

    This population-based cohort study comprised 41,669 children born in gestational weeks 32-40 in Uppsala County, Sweden, between 2000 and 2015. We applied a generalized least squares model including anthropometric measurements at 1.5, 3, 4 and 5 years. We calculated estimated mean height, weight and BMI for children born in week 32+0, 35+0 or 40+0 with birthweight 50th percentile (standardized appropriate for gestational age, sAGA) or 3rd percentile (standardized small for gestational age, sSGA).

    Compared with children born sAGA at gestational week 40+0, those born sAGA week 32+0 or 35+0 had comparable estimated mean height, weight and BMI after 3 years of age. Making the same comparison, those born sSGA week 32+0 or 35+0 were shorter and lighter with lower estimated mean BMI throughout the whole follow-up period.

    Our findings suggest that being born SGA and moderate preterm is associated with short stature and low BMI during the first five years of life. The association seemed stronger the shorter gestational age at birth.

  • 255. Liu, Ruishan
    et al.
    Mignardi, Marco
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Jones, Robert
    Enge, Martin
    Kim, Seung K.
    Quake, Stephen R.
    Zou, James
    Modeling spatial correlation of transcripts with application to developing pancreas2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 5592Article in journal (Refereed)
  • 256.
    Lizarraga, Raquel
    et al.
    Royal Inst Technol KTH, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden..
    Pan, Fan
    Royal Inst Technol KTH, Sch Informat & Commun Technol, Dept Mat & Nano Phys, Electrum 229, SE-16440 Kista, Sweden.;Royal Inst Technol KTH, Swedish E Sci Res Ctr, SE-10044 Stockholm, Sweden..
    Bergqvist, Lars
    Royal Inst Technol KTH, Sch Informat & Commun Technol, Dept Mat & Nano Phys, Electrum 229, SE-16440 Kista, Sweden.;Royal Inst Technol KTH, Swedish E Sci Res Ctr, SE-10044 Stockholm, Sweden..
    Holmström, Erik
    Sandvik Coromant R&D, SE-12680 Stockholm, Sweden..
    Gercsi, Zsolt
    Trinity Coll Dublin, Sch Phys, Dublin 2, Ireland.;Trinity Coll Dublin, CRANN, Dublin 2, Ireland..
    Vitos, Levente
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory. Royal Inst Technol KTH, Dept Mat Sci & Engn, Appl Mat Phys, SE-10044 Stockholm, Sweden.; Wigner Res Ctr Phys, Res Inst Solid State Phys & Opt, POB 49, H-1525 Budapest, Hungary.
    First Principles Theory of the hcp-fcc Phase Transition in Cobalt2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3778Article in journal (Refereed)
    Abstract [en]

    Identifying the forces that drive a phase transition is always challenging. The hcp-fcc phase transition that occurs in cobalt at similar to 700 K has not yet been fully understood, although early theoretical studies have suggested that magnetism plays a main role in the stabilization of the fcc phase at high temperatures. Here, we perform a first principles study of the free energies of these two phases, which we break into contributions arising from the vibration of the lattice, electronic and magnetic systems and volume expansion. Our analysis of the energy of the phases shows that magnetic effects alone cannot drive the fcc-hcp transition in Co and that the largest contribution to the stabilization of the fcc phase comes from the vibration of the ionic lattice. By including all the contributions to the free energy considered here we obtain a theoretical transition temperature of 825 K.

  • 257.
    Loley, Christina
    et al.
    Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, Lubeck, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
    Assimes, Themistocles L.
    Stanford Univ, Sch Med Stanford, Dept Med, Div Cardiovasc Med, Stanford, CA USA..
    Bjonnes, Andrew
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Goel, Anuj
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Heart Hosp, Dept Cariol, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Lau, King Wai
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Nikpay, Majid
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Qu, Liming
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Salfati, Elias
    Stanford Univ, Sch Med Stanford, Dept Med, Div Cardiovasc Med, Stanford, CA USA..
    Scholz, Markus
    Univ Leipzig, Fac Med, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.;LIFE Res Ctr Civilizat Dis, Leipzig, Germany..
    Tukiainen, Taru
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Willenborg, Christina
    DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany.;Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Integrat & Expt Genom, Campus Lubeck, Lubeck, Germany.;Univ Heart Ctr Luebeck, Campus Lubeck, Lubeck, Germany..
    Won, Hong-Hee
    Sungkyunkwan Univ, Samsung Med Ctr, SAIHST, Seoul, South Korea..
    Zeng, Lingyao
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England..
    Anand, Sonia S.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Beutner, Frank
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Leipzig, Heart Ctr Leipzig, Cardiol, Leipzig, Germany..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Clarke, Robert
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Dedoussis, George
    Harokopio Univ Athens, Athens, Greece..
    Do, Ron
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Ctr Stat Genet, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Zena & Michael A Weiner Cardiovasc Inst, New York, NY 10029 USA..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Eskola, Markku
    Heart Hosp, Dept Cariol, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Farrall, Martin
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gauguier, Dominique
    INSERM, Ctr Rech Cordeliers, UMRS1138, Paris, France..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Granger, Christopher B.
    Duke Univ, Sch Med, Durham, NC USA..
    Hall, Alistair S.
    Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Hazen, Stanley L.
    Cleveland Clin, Cleveland, OH 44106 USA..
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere, Finland..
    Kyriakou, Theodosios
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Laaksonen, Reijo
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland.;Zora Biosci, Espoo, Finland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Marouli, Eirini
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Nikus, Kjell
    Heart Hosp, Dept Cariol, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Pedersen, Nancy
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Rallidis, Loukianos
    Univ Gen Hosp Attikon, Dept Cardiol 2, Athens, Greece..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Shah, Svati H.
    Duke Univ, Sch Med, Durham, NC USA..
    Stewart, Alexandre F. R.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Thompson, John R.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Zalloua, Pierre A.
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon.;Harvard Sch Publ Hlth, Boston, MA USA..
    Chambers, John C.
    Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Imperial Coll Healthcare NHS Trust, London, England..
    Collins, Rory
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Iribarren, Carlos
    Kaiser Permanente, Div Res, Oakland, CA USA..
    Karhunen, Pekka J.
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Forens Med, Tampere, Finland..
    Kooner, Jaspal S.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Cardiovasc Sci, Natl Heart & Lung Inst, London, England..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.;Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    McPherson, Ruth
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
    Reilly, Muredach P.
    Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Ripatti, Samuli
    Kaiser Permanente, Div Res, Oakland, CA USA.;Univ Helsinki, Hjelt Inst, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA.;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA.;Oklahoma Ctr Neurosci, Oklahoma City, OK USA..
    Thiery, Joachim
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Hosp Leipzig, Fac Med, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany..
    Watkins, Hugh
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Wellcome Trust Sanger Inst, Cambridge, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Schunkert, Heribert
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.;Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Erdmann, Jeanette
    DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany.;Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Integrat & Expt Genom, Campus Lubeck, Lubeck, Germany.;Univ Heart Ctr Luebeck, Campus Lubeck, Lubeck, Germany..
    Koenig, Inke R.
    Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, Lubeck, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany..
    No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35278Article in journal (Refereed)
    Abstract [en]

    In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.

  • 258. Lu, Junchang
    et al.
    Pu, Hanyong
    Kobayashi, Yoshitsugu
    Xu, Li
    Chang, Huali
    Shang, Yuhua
    Liu, Di
    Lee, Yuong-Nam
    Kundrat, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Shen, Caizhi
    A New Oviraptorid Dinosaur (Dinosauria: Oviraptorosauria) from the Late Cretaceous of Southern China and Its Paleobiogeographical Implications2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 11490Article in journal (Refereed)
    Abstract [en]

    The Ganzhou area of Jiangxi Province, southern China is becoming one of the most productive oviraptorosaurian localities in the world. A new oviraptorid dinosaur was unearthed from the uppermost Upper Cretaceous Nanxiong Formation of Ganzhou area. It is characterized by an anterodorsally sloping occiput and quadrate (a feature shared with Citipati), a circular supratemporal fenestra that is much smaller than the lower temporal fenestra, and a dentary in which the dorsal margin above the external mandibular fenestra is strongly concave ventrally. The position of the anteroventral corner of the external naris in relation to the posterodorsal corner of the antorbital fenestra provides new insight into the craniofacial evolution of oviraptorosaurid dinosaurs. A phylogenetic analysis recovers the new taxon as closely related to the Mongolian Citipati. Six oviraptorid dinosaurs from the Nanxiong Formation (Ganzhou and Nanxiong) are distributed within three clades of the family. Each of the three clades from the Nanxiong Formation has close relatives in Inner Mongolia and Mongolia, and in both places each clade may have had a specific diet or occupied a different ecological niche. Oviraptorid dinosaurs were geographically widespread across Asia in the latest Cretaceous and were an important component of terrestrial ecosystems during this time.

  • 259.
    Ludvigsson, Maria Landen
    et al.
    Linkoping Univ, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden;Linkoping Univ, Dept Rehabil, Cty Council Ostergotland, Rehab Vast, Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, 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, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden .
    Peolsson, Anneli
    Linkoping Univ, Dept Med & Hlth Sci, Div Physiotherapy, Linkoping, Sweden.
    Neck-specific exercise may reduce radiating pain and signs of neurological deficits in chronic whiplash: Analyses of a randomized clinical trial2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12409Article in journal (Refereed)
    Abstract [en]

    Up to 90% of people with neurological deficits following a whiplash injury do not recover and cervical muscle dysfunction is common. The aim of this multicentre, randomized controlled trial was to examine whether two versions of neck-specific exercise or prescription of physical activity (PPA) can improve radiating arm pain and clinical signs that can be associated with neurological deficits in people with chronic whiplash associated disorders (WAD). Participants with chronic WAD, arm symptoms and signs associated with neurological deficits (n = 171) were randomized to: 12 weeks of neck-specific exercise without (NSE) or with a behavioural approach (NSEB), or PPA. Pain/bothersomeness frequency, six measures of arm pain/paraesthesia (VAS scales), and four clinical neurological tests were evaluated after 3 months. The NSE group reported the lowest frequency and lowest levels of arm pain, the highest proportion of participants with at least 50% pain reduction and the highest proportion of normal arm muscle force. The NSEB group reported increased normal tendon reflexes. No improvements were recorded for the PPA group. Neck-specific exercise may improve arm pain and decrease signs of neurological deficits, but the addition of a behavioural approach does not seem to be of additional benefit.

  • 260. Lundholm, Marie
    et al.
    Hägglöf, Christina
    Wikberg, Maria L
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Egevad, Lars
    Bergh, Anders
    Wikström, Pernilla
    Palmqvist, Richard
    Edin, Sofia
    Secreted Factors from Colorectal and Prostate Cancer Cells Skew the Immune Response in Opposite Directions.2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15651Article in journal (Refereed)
    Abstract [en]

    Macrophage infiltration has been associated with an improved prognosis in patients with colorectal cancer (CRC), but a poor prognosis in prostate cancer (PC) patients. In this study, the distribution and prognostic value of proinflammatory M1 macrophages (NOS2(+)) and immunosuppressive M2 macrophages (CD163(+)) was evaluated in a cohort of 234 PC patients. We found that macrophages infiltrating PC were mainly of an M2 type and correlated with a more aggressive tumor and poor patient prognosis. Furthermore, the M1/M2 ratio was significantly decreased in PC compared to CRC. Using in vitro cell culture experiments, we could show that factors secreted from CRC and PC cells induced macrophages of a proinflammatory or immunosuppressive phenotype, respectively. These macrophages differentially affected autologous T lymphocyte proliferation and activation. Consistent with this, CRC specimens were found to have higher degrees of infiltrating T-helper 1 cells and active cytotoxic T lymphocytes, while PC specimens displayed functionally inactive T cells. In conclusion, our results imply that tumour-secreted factors from cancers of different origin can drive macrophage differentiation in opposite directions and thereby regulate the organization of the anti-tumour immune response. Our findings suggest that reprogramming of macrophages could be an important tool in the development of new immunotherapeutic strategies.

  • 261.
    Lundström, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Weghuber, Daniel
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal.
    Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3064Article in journal (Refereed)
    Abstract [en]

    Human brown adipose tissue (BAT), with a major site in the cervical-supraclavicular depot, is a promising anti-obesity target. This work presents an automated method for segmenting cervical-supraclavicular adipose tissue for enabling time-efficient and objective measurements in large cohort research studies of BAT. Fat fraction (FF) and R2* maps were reconstructed from water-fat magnetic resonance imaging (MRI) of 25 subjects. A multi-atlas approach, based on atlases from nine subjects, was chosen as automated segmentation strategy. A semi-automated reference method was used to validate the automated method in the remaining subjects. Automated segmentations were obtained from a pipeline of preprocessing, affine registration, elastic registration and postprocessing. The automated method was validated with respect to segmentation overlap (Dice similarity coefficient, Dice) and estimations of FF, R2* and segmented volume. Bias in measurement results was also evaluated. Segmentation overlaps of Dice = 0.93 +/- 0.03 (mean +/- standard deviation) and correlation coefficients of r > 0.99 (P < 0.0001) in FF, R2* and volume estimates, between the methods, were observed. Dice and BMI were positively correlated (r = 0.54, P = 0.03) but no other significant bias was obtained (P >= 0.07). The automated method compared well with the reference method and can therefore be suitable for time-efficient and objective measurements in large cohort research studies of BAT.

  • 262.
    Löf, Liza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Arngården, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Olsson-Strömberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Siart, Benjamin
    Jansson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dahlin, Joakim S
    Thörn, Ingrid
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Christiansson, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hermansson, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ahlstrand, Erik
    Wålinder, Göran
    Söderberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Landegren, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    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.
    Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, p. 1-9, article id 623Article in journal (Refereed)
    Abstract [en]

    Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.

  • 263.
    Löf, Liza
    et al.
    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.
    Ebai, Tonge
    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.
    Dubois, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wik, Lotta
    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.
    Ronquist, K. Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Nolander, Olivia
    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.
    Lundin, Emma
    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.
    Söderberg, Ola
    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.
    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.
    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.
    Detecting individual extracellular vesicles using a multicolor in situ proximity ligation assay with flow cytometric readout2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 34358Article in journal (Refereed)
    Abstract [en]

    Flow cytometry is a powerful method for quantitative and qualitative analysis of individual cells. However, flow cytometric analysis of extracellular vesicles (EVs), and the proteins present on their surfaces has been hampered by the small size of the EVs - in particular for the smallest EVs, which can be as little as 40 nm in diameter, the limited number of antigens present, and their low refractive index. We addressed these limitations for detection and characterization of EV by flow cytometry through the use of multiplex and multicolor in situ proximity ligation assays (in situ PLA), allowing each detected EV to be easily recorded over background noise using a conventional flow cytometer. By targeting sets of proteins on the surface that are specific for distinct classes of EVs, the method allows for selective recognition of populations of EVs in samples containing more than one type of EVs. The method presented herein opens up for analyses of EVs using flow cytometry for their characterization and quantification.

  • 264.
    Lönn, Peter
    et al.
    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. Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA..
    Kacsinta, Apollo D.
    Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA..
    Cui, Xian-Shu
    Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA..
    Hamil, Alexander S.
    Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA..
    Kaulich, Manuel
    Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA.;Goethe Univ Frankfurt, Inst Biochem 2, Frankfurt, Germany..
    Gogoi, Khirud
    Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA.;AM Chem, Oceanside, CA 92056 USA..
    Dowdy, Steven F.
    Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, La Jolla, CA 92093 USA..
    Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 32301Article in journal (Refereed)
    Abstract [en]

    Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

  • 265. Lönnstedt, Oona M.
    et al.
    McCormick, Mark I.
    Chivers, Douglas P.
    Predator-induced changes in the growth of eyes and false eyespots2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 2259-Article in journal (Refereed)
  • 266.
    Maack, Heidrun Petursdottir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Sjöholm, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eurenius-Orre, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Mulic-Lutvica, Ajlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Maternal body mass index moderates antenatal depression effects on infant birthweight2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 6213Article in journal (Refereed)
    Abstract [en]

    Obesity and depression are two common medical problems that pregnant women present with in antenatal care. Overweight and obesity at the beginning of the pregnancy, and excessive weight gain during pregnancy, are independent explanatory variables for fetal birthweight and independent risk factors for giving birth to a large for gestational age (LGA) infant. However, the effect of co-morbid depression has received little attention. This study set out to investigate if maternal body mass index (BMI) in early pregnancy moderates antenatal depression effects on infant birthweight. 3965 pregnant women participated in this longitudinal cohort study, where cases (n = 178) had Edinburgh Postnatal Depression Scale (EPDS) score >= 17 in gestational week 17 or 32, and remaining women (n = 3787) were used as controls. The influence of maternal BMI and antenatal depressive symptoms on standardized birthweight was evaluated by analysis of covariance, with adjustment for relevant confounders. Depressed women with BMI 25.0 kg/m(2) or more gave birth to infants with significantly greater standardized birthweight than non-depressed overweight women, whereas the opposite pattern was noted in normal weight women (BMI by antenatal depressive symptoms interaction; F(1,3839) = 6.32; p = 0.012. The increased birthweight in women with co-prevalent overweight and depressive symptoms was not explained by increased weight gain during the pregnancy. Maternal BMI at the beginning of pregnancy seems to influence the association between antenatal depressive symptoms and infant birthweight, but in opposite directions depending on whether the pregnant women is normal weight or overweight. Further studies are needed to confirm our finding.

  • 267. Maddock, Jane
    et al.
    Zhou, Ang
    Cavadino, Alana
    Kuźma, Elżbieta
    Bao, Yanchun
    Smart, Melissa C
    Saum, Kai-Uwe
    Schöttker, Ben
    Engmann, Jorgen
    Kjærgaard, Marie
    Karhunen, Ville
    Zhan, Yiqiang
    Lehtimäki, Terho
    Rovio, Suvi P
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lahti, Jari
    Marques-Vidal, Pedro
    Sen, Abhijit
    Perna, Laura
    Schirmer, Henrik
    Singh-Manoux, Archana
    Auvinen, Juha
    Hutri-Kähönen, Nina
    Kähönen, Mika
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Räikkönen, Katri
    Melhus, Håkan
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Guessous, Idris
    Petrovic, Katja E
    Schmidt, Helena
    Schmidt, Reinhold
    Vollenweider, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Eriksson, Johan G
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Raitakari, Olli T
    Hägg, Sara
    Pedersen, Nancy L
    Herzig, Karl-Heinz
    Järvelin, Marjo-Riitta
    Veijola, Juha
    Kivimaki, Mika
    Jorde, Rolf
    Brenner, Hermann
    Kumari, Meena
    Power, Chris
    Llewellyn, David J
    Hyppönen, Elina
    Vitamin D and cognitive function: A Mendelian randomisation study.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13230Article in journal (Refereed)
    Abstract [en]

    The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

  • 268.
    Maessen, Sarah E.
    et al.
    Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Cutfield, Wayne S.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Univ Auckland, Better Start Natl Sci Challenge, Auckland, New Zealand.
    Derraik, Jose G. B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Auckland, Liggins Inst, Auckland, New Zealand;Univ Auckland, Better Start Natl Sci Challenge, Auckland, New Zealand.
    Maternal smoking early in pregnancy is associated with increased risk of short stature and obesity in adult daughters2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 4290Article in journal (Refereed)
    Abstract [en]

    We assessed anthropometry in 22,421 adult daughters in association with their mothers' tobacco smoking early in pregnancy (at their first antenatal visit) in Sweden, particularly their risk of short stature and obesity. Adult daughters were grouped by maternal smoking levels during pregnancy: Nonsmokers (58.5%), Light smokers (24.1%; smoked 1-9 cigarettes/day), and Heavier smokers (17.4%; smoked >= 10 cigarettes/day). Anthropometry was recorded on the adult daughters at approximately 26.0 years of age. Obesity was defined as BMI >= 30 kg/m(2), and short stature as height more than two standard deviations below the population mean. Daughters whose mothers were Light and Heavier smokers in early pregnancy were 0.8 cm and 1.0cm shorter, 2.3 kg and 2.6 kg heavier, and had BMI 0.84 kg/m(2) and 1.15 kg/m(2) greater, respectively, than daughters of Non-smokers. The adjusted relative risk of short stature was 55% higher in women born to smokers, irrespectively of smoking levels. Maternal smoking had a dose-dependent association with obesity risk, with offspring of Heavier smokers 61% and of Light smokers 37% more likely to be obese than the daughters of Non-smokers. In conclusion, maternal smoking in pregnancy was associated with an increased risk of short stature and obesity in their adult daughters.

  • 269. Magnuson, Martin
    et al.
    Schmitt, Thorsten
    Strocov, Vladimir N.
    Schlappa, Justina
    Kalabukhov, Alexej S.
    Duda, Laurent-Claudius
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Self-doping processes between planes and chains in the metal-to-superconductor transition of YBa2Cu3O6.92014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 7017-Article in journal (Refereed)
    Abstract [en]

    The interplay between the quasi 1-dimensional CuO-chains and the 2-dimensional CuO2 planes of YBa2Cu3O61x (YBCO) has been in focus for a long time. Although the CuO-chains are known to be important as charge reservoirs that enable superconductivity for a range of oxygen doping levels in YBCO, the understanding of the dynamics of its temperature-driven metal-superconductor transition (MST) remains a challenge. We present a combined study using x-ray absorption spectroscopy and resonant inelastic x-ray scattering (RIXS) revealing how a reconstruction of the apical O(4)-derived interplanar orbitals during the MST of optimally doped YBCO leads to substantial hole-transfer from the chains into the planes, i.e. self-doping. Our ionic model calculations show that localized divalent charge-transfer configurations are expected to be abundant in the chains of YBCO. While these indeed appear in the RIXS spectra from YBCO in the normal, metallic, state, they are largely suppressed in the superconducting state and, instead, signatures of Cu trivalent charge-transfer configurations in the planes become enhanced. In the quest for understanding the fundamental mechanism for high-Tc-superconductivity (HTSC) in perovskite cuprate materials, the observation of such an interplanar self-doping process in YBCO opens a unique novel channel for studying the dynamics of HTSC.

  • 270.
    Maharjan, Rajani
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Backman, Samuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Comprehensive analysis of CTNNB1 in adrenocortical carcinomas: Identification of novel mutations and correlation to survival2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8610Article in journal (Refereed)
    Abstract [en]

    The Wnt/β-Catenin signaling pathway is one of the most frequently altered pathways in adrenocortical carcinomas (ACCs). The aim of this study was to investigate the status of Wnt/β-Catenin signaling pathway by analyzing the expression level of β-Catenin and the mutational status of APC, AXIN2, CTNNB1, and ZNRF3 in ACCs. Mutations in APC, CTNNB1, ZNRF3 and homozygous deletions in ZNRF3 were observed in 3.8% (2/52), 11.5% (6/52), 1.9% (1/52) and 17.3% (9/52) of the cohort respectively. Novel interstitial deletions in CTNNB1 spanning intron 1 to exon 3/intron 3 were also found in 7.7% (4/52) of the tumours. All the observed alterations were mutually exclusive. Nuclear accumulation of β-Catenin, increased expression of Cyclin D1 and significantly higher expression of AXIN2 (p = 0.0039), ZNRF3 (p = 0.0032) and LEF1(p = 0.0090) observed in the tumours harbouring the deletion in comparison to tumours without CTNNB1 mutation demonstrates that the truncated β-Catenin is functionally active and erroneously activates the downstream targets. Significantly lower overall survival rate in patients with tumours harbouring alterations in APC/CTNNB1/ZNRF3 in comparison to those without mutation was observed. In conclusion, the discovery of novel large deletions in addition to the point mutations in CTNNB1 infers that activation of Wnt/β-Catenin pathway via alterations in CTNNB1 occurs frequently in ACCs. We also confirm that alterations in Wnt/β-Catenin signaling pathway members have a negative effect on overall survival of patients.

  • 271.
    Makita, M.
    et al.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Vartiainen, I.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Mohacsi, I.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland;LOrme Merisiers, Synchrotron SOLEIL, F-91190 Saint Aubin, France.
    Caleman, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics. Deutsch Elektronen Synchrotron DESY, CFEL, D-22667 Hamburg, Germany.
    Diaz, A.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Jönsson, Olof
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics. KTH Royal Inst Technol, Dept Appl Phys, SE-10691 Stockholm, Sweden.
    Juranic, P.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Medvedev, N.
    Czech Acad Sci, Inst Phys, Prague 18221 8, Czech Republic;Czech Acad Sci, Inst Plasma Phys, Prague 18200 8, Czech Republic.
    Meents, A.
    Deutsch Elektronen Synchrotron DESY, CFEL, D-22667 Hamburg, Germany.
    Mozzanica, A.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Opara, N. L.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland;Univ Basel, C CINA Biozentrum, CH-4058 Basel, Switzerland.
    Padeste, C.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Panneels, V.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Saxena, V.
    Deutsch Elektronen Synchrotron DESY, CFEL, D-22667 Hamburg, Germany;Bhat, Inst Plasma Res, Gandhinagar 382428, India.
    Sikorski, M.
    SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
    Song, S.
    Vera, L.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Willmott, P. R.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Beaud, P.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Milne, C. J.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Ziaja-Motyka, B.
    Deutsch Elektronen Synchrotron DESY, CFEL, D-22667 Hamburg, Germany;Polish Acad Sci, Inst Nucl Phys, PL-31342 Krakow, Poland.
    David, C.
    Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
    Femtosecond phase-transition in hard x-ray excited bismuth2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 602Article in journal (Refereed)
    Abstract [en]

    The evolution of bismuth crystal structure upon excitation of its A(1g) phonon has been intensely studied with short pulse optical lasers. Here we present the first-time observation of a hard x-ray induced ultrafast phase transition in a bismuth single crystal at high intensities (similar to 10(14) W/cm(2)). The lattice evolution was followed using a recently demonstrated x-ray single-shot probing setup. The time evolution of the (111) Bragg peak intensity showed strong dependence on the excitation fluence. After exposure to a sufficiently intense x-ray pulse, the peak intensity dropped to zero within 300 fs, i.e. faster than one oscillation period of the A(1g) mode at room temperature. Our analysis indicates a nonthermal origin of a lattice disordering process, and excludes interpretations based on electron-ion equilibration process, or on thermodynamic heating process leading to plasma formation.

  • 272.
    Malehmir, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Maries, Georgiana
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Backstrom, Emma
    Nord Iron Ore AB, Ludvika, Sweden..
    Schon, Monika
    Nord Iron Ore AB, Ludvika, Sweden..
    Marsden, Paul
    Nord Iron Ore AB, Ludvika, Sweden..
    Developing cost-effective seismic mineral exploration methods using a landstreamer and a drophammer2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10325Article in journal (Refereed)
    Abstract [en]

    To be fully embraced into mineral exploration, seismic data require to be acquired fast, cheaper and with minimum environmental impacts addressing also the often brown-field highly noisy environment where these surveys are employed. Since 2013 and through a number of case studies, we have been testing a newly developed for urban environment, digital-based 240 m long, seismic landstreamer for mine planning and mineral exploration purposes. Here, we present a pilot study examining the potential of the streamer for deep targeting a known, down to approximately 850 m depth, iron-oxide mineralization in the Bergslagen mineral district of central Sweden. Combined streamer (100-3C-MEMS (micro-electromechanical system), 2-4 m spacing) and 75 wireless recorders (mixed 10 Hz and MEMS, 10 m spacing) were used. A Bobcat-mounted drophammer,500 kg, was used to generate the seismic signal. Within 4 days, approximately 3.5 km of seismic data using 2-10 m source and receiver spacing were acquired. Reflection data processing results clearly image the mineralization as a set of strong high-amplitude reflections and likely slightly extending beyond the known 850 m depth. This is encouraging and suggests such a cost-effective exploration method can be used in the area and elsewhere to delineate similar depth range iron-oxide deposits.

  • 273.
    Malehmir, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Maries, Georgiana
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Bäckstrom, Emma
    Nord Iron Ore AB, Ludvika, Sweden..
    Schön, Monika
    Nord Iron Ore AB, Ludvika, Sweden..
    Marsden, Paul
    Nord Iron Ore AB, Ludvika, Sweden..
    Developing cost-effective seismic mineral exploration methods using a landstreamer and a drophammer2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10325Article in journal (Refereed)
    Abstract [en]

    To be fully embraced into mineral exploration, seismic data require to be acquired fast, cheaper and with minimum environmental impacts addressing also the often brown-field highly noisy environment where these surveys are employed. Since 2013 and through a number of case studies, we have been testing a newly developed for urban environment, digital-based 240 m long, seismic landstreamer for mine planning and mineral exploration purposes. Here, we present a pilot study examining the potential of the streamer for deep targeting a known, down to approximately 850 m depth, iron-oxide mineralization in the Bergslagen mineral district of central Sweden. Combined streamer (100-3C-MEMS (micro-electromechanical system), 2-4 m spacing) and 75 wireless recorders (mixed 10 Hz and MEMS, 10 m spacing) were used. A Bobcat-mounted drophammer,500 kg, was used to generate the seismic signal. Within 4 days, approximately 3.5 km of seismic data using 2-10 m source and receiver spacing were acquired. Reflection data processing results clearly image the mineralization as a set of strong high-amplitude reflections and likely slightly extending beyond the known 850 m depth. This is encouraging and suggests such a cost-effective exploration method can be used in the area and elsewhere to delineate similar depth range iron-oxide deposits.

  • 274.
    Manzetti, Sergio
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Fjordforsk A/S.
    Derivation and Numerical analysis of an Attenuation Operator for non-relativistic waves2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16572Article in journal (Refereed)
    Abstract [en]

    Quantum mechanical models for particles are strictly dependent on the Schrödinger equation, where the solutions and the Hermitian polynomials form a mathematical foundation to derive expectation values for observables. As for all quantum systems, the solutions are derived in discrete energy levels, and yield probability density, the kinetic energy and average momentum. In this study however, an attenuation Hamiltonian is derived by the algebraic relation of the momentum and position operators, and the derived equation, where the attenuation of kinetic energy is the eigenvalue, is studied numerically. The numerical solutions suggest that the change in kinetic energy from one transition to the next proceed in an undular fashion, and not in a definite manner. This suggests that any sub-atomic particle which experiences a transition from one level to the next, does so by both gaining and losing energy in an undular manner before reaching an equilibrium with a new and stabilized kinetic energy. The results show also that the phase of the change in kinetic energy between transitions differs between high and low momenta and that higher levels of momentum attenuate more smoothly than transitions between lower energy levels. The investigated attenuation operator may be important for future pinning and quasipinning approaches and play a role in future quantum information processing. Future research is required on the spectrum of the operator and on its potential analytical solutions.

  • 275.
    Marti, J.
    et al.
    CSIC, Inst Earth Sci Jaume Almera, ICTJA, Barcelona, Spain..
    Villasenor, A.
    CSIC, Inst Earth Sci Jaume Almera, ICTJA, Barcelona, Spain..
    Geyer, A.
    CSIC, Inst Earth Sci Jaume Almera, ICTJA, Barcelona, Spain..
    Lopez, C.
    IGN, Observ Geofis Cent, Madrid, Spain..
    Tryggvason, Ari
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Geophysics.
    Stress barriers controlling lateral migration of magma revealed by seismic tomography2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 40757Article in journal (Refereed)
    Abstract [en]

    Understanding how monogenetic volcanic systems work requires full comprehension of the local and regional stresses that govern magma migration inside them and why/how they seem to change from one eruption to another. During the 2011-2012 El Hierro eruption (Canary Islands) the characteristics of unrest, including a continuous change in the location of seismicity, made the location of the future vent unpredictable, so short term hazard assessment was highly imprecise. A 3D P-wave velocity model is obtained using arrival times of the earthquakes occurred during that pre-eruptive unrest and several latter post-eruptive seismic crises not related to further eruptions. This model reveals the rheological and structural complexity of the interior of El Hierro volcanic island. It shows a number of stress barriers corresponding to regional tectonic structures and blocked pathways from previous eruptions, which controlled ascent and lateral migration of magma and, together with the existence of N-S regional compression, reduced its options to find a suitable path to reach the surface and erupt.

  • 276.
    Mashkoori, Mahdi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Björnson, Kristofer
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Black-Schaffer, Annica M.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Impurity bound states in fully gapped d-wave superconductors with subdominant order parameters2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4107Article in journal (Refereed)
    Abstract [en]

    Impurities in superconductors and their induced bound states are important both for engineering novel states such as Majorana zero-energy modes and for probing bulk properties of the superconducting state. The high-temperature cuprates offer a clear advantage in a much larger superconducting order parameter, but the nodal energy spectrum of a pure d-wave superconductor only allows virtual bound states. Fully gapped d-wave superconducting states have, however, been proposed in several cuprate systems thanks to subdominant order parameters producing d + is- or d + id'-wave superconducting states. Here we study both magnetic and potential impurities in these fully gapped d-wave superconductors. Using analytical T-matrix and complementary numerical tight-binding lattice calculations, we show that magnetic and potential impurities behave fundamentally different in d + is- and d + id'-wave superconductors. In a d + is-wave superconductor, there are no bound states for potential impurities, while a magnetic impurity produces one pair of bound states, with a zero-energy level crossing at a finite scattering strength. On the other hand, a d + id'-wave symmetry always gives rise to two pairs of bound states and only produce a reachable zero-energy level crossing if the normal state has a strong particle-hole asymmetry.

  • 277.
    Mateus, André
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Treyer, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Wegler, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. AstraZeneca R&D, Cardiovasc & Metab Dis Innovat Med, DMPK, SE-43183 Molndal, Sweden..
    Karlgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Matsson, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Intracellular drug bioavailability: a new predictor of system dependent drug disposition2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, p. 1-12, article id 43047Article in journal (Refereed)
    Abstract [en]

    Intracellular drug exposure is influenced by cell-and tissue-dependent expression of drug-transporting proteins and metabolizing enzymes. Here, we introduce the concept of intracellular bioavailability (F-ic) as the fraction of extracellular drug available to bind intracellular targets, and we assess how Fic is affected by cellular drug disposition processes. We first investigated the impact of two essential drug transporters separately, one influx transporter (OATP1B1; SLCO1B1) and one efflux transporter (P-gp; ABCB1), in cells overexpressing these proteins. We showed that OATP1B1 increased Fic of its substrates, while P-gp decreased Fic. We then investigated the impact of the concerted action of multiple transporters and metabolizing enzymes in freshly-isolated human hepatocytes in culture configurations with different levels of expression and activity of these proteins. We observed that Fic was up to 35-fold lower in the configuration with high expression of drug-eliminating transporters and enzymes. We conclude that Fic provides a measurement of the net impact of all cellular drug disposition processes on intracellular bioavailable drug levels. Importantly, no prior knowledge of the involved drug distribution pathways is required, allowing for high-throughput determination of drug access to intracellular targets in highly defined cell systems (e.g., single-transporter transfectants) or in complex ones (including primary human cells).

  • 278.
    Matricon, Pierre
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ranganathan, Anirudh
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, SE-10691 Stockholm, Sweden..
    Warnick, Eugene
    NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA..
    Gao, Zhan-Guo
    NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA..
    Rudling, Axel
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, SE-10691 Stockholm, Sweden..
    Lambertucci, Catia
    Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy..
    Marucci, Gabriella
    Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy..
    Ezzati, Aitakin
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, SE-10691 Stockholm, Sweden..
    Jaiteh, Mariama
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dal Ben, Diego
    Univ Camerino, Scuola Sci Farmaco & Prod Salute, Via S Agostino 1, I-62032 Camerino, MC, Italy..
    Jacobson, Kenneth A.
    NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA..
    Carlsson, Jens
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Fragment optimization for GPCRs by molecular dynamics free energy calculations: Probing druggable subpockets of the A(2A) adenosine receptor binding site2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6398Article in journal (Refereed)
    Abstract [en]

    Fragment-based lead discovery is becoming an increasingly popular strategy for drug discovery. Fragment screening identifies weakly binding compounds that require optimization to become high-affinity leads. As design of leads from fragments is challenging, reliable computational methods to guide optimization would be invaluable. We evaluated using molecular dynamics simulations and the free energy perturbation method (MD/FEP) in fragment optimization for the A(2A) adenosine receptor, a pharmaceutically relevant G protein-coupled receptor. Optimization of fragments exploring two binding site subpockets was probed by calculating relative binding affinities for 23 adenine derivatives, resulting in strong agreement with experimental data (R-2 = 0.78). The predictive power of MD/FEP was significantly better than that of an empirical scoring function. We also demonstrated the potential of the MD/FEP to assess multiple binding modes and to tailor the thermodynamic profile of ligands during optimization. Finally, MD/FEP was applied prospectively to optimize three nonpurine fragments, and predictions for 12 compounds were evaluated experimentally. The direction of the change in binding affinity was correctly predicted in a majority of the cases, and agreement with experiment could be improved with rigorous parameter derivation. The results suggest that MD/FEP will become a powerful tool in structure-driven optimization of fragments to lead candidates.

  • 279. Mattesini, M.
    et al.
    Belonoshko, A. B.
    Tkalcic, H.
    Buforn, E.
    Udias, A.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Candy Wrapper for the Earth's Inner Core2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 2096-Article in journal (Refereed)
    Abstract [en]

    Recent global expansion of seismic data motivated a number of seismological studies of the Earth's inner core that proposed the existence of increasingly complex structure and anisotropy. In the meantime, new hypotheses of dynamic mechanisms have been put forward to interpret seismological results. Here, the nature of hemispherical dichotomy and anisotropy is re-investigated by bridging the observations of PKP(bc-df) differential travel-times with the iron bcc/hcp elastic properties computed from first-principles methods. The Candy Wrapper velocity model introduced here accounts for a dynamic picture of the inner core (i.e., the eastward drift of material), where different iron crystal shapes can be stabilized at the two hemispheres. We show that seismological data are best explained by a rather complicated, mosaic-like, structure of the inner core, where well-separated patches of different iron crystals compose the anisotropic western hemispherical region, and a conglomerate of almost indistinguishable iron phases builds-up the weakly anisotropic eastern side.

  • 280.
    Mayrhofer, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, SE-17177 Stockholm, Sweden.
    Viklund, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Isaksson, Anders
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Rawcopy: Improved copy number analysis with Affymetrix arrays2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36158Article in journal (Refereed)
    Abstract [en]

    Microarray data is subject to noise and systematic variation that negatively affects the resolution of copy number analysis. We describe Rawcopy, an R package for processing of Affymetrix CytoScan HD, CytoScan 750k and SNP 6.0 microarray raw intensities (CEL files). Noise characteristics of a large number of reference samples are used to estimate log ratio and B-allele frequency for total and allele-specific copy number analysis. Rawcopy achieves better signal-to-noise ratio and higher proportion of validated alterations than commonly used free and proprietary alternatives. In addition, Rawcopy visualizes each microarray sample for assessment of technical quality, patient identity and genome-wide absolute copy number states. Software and instructions are available at http://rawcopy.org.

  • 281.
    Metsanurk, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Tamm, A.
    Caro, A.
    Aabloo, A.
    Klintenberg, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    First-principles study of point defects at a semicoherent interface2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, p. 7567-Article in journal (Refereed)
    Abstract [en]

    Most of the atomistic modeling of semicoherent metal-metal interfaces has so far been based on the use of semiempirical interatomic potentials. We show that key conclusions drawn from previous studies are in contradiction with more precise ab-initio calculations. In particular we find that single point defects do not delocalize, but remain compact near the interfacial plane in Cu-Nb multilayers. We give a simple qualitative explanation for this difference on the basis of the well known limited transferability of empirical potentials.

  • 282.
    Mezheyeuski, Artur
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus..
    Hrynchyk, Ina
    City Clin Pathologoanat Bur, Minsk, Byelarus..
    Karlberg, Mia
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Portyanko, Anna
    Belarusian State Med Univ, Dept Pathol, Minsk, Byelarus..
    Egevad, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Ragnhammar, Peter
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Edler, David
    Karolinska Univ Hosp Solna, Dept Mol Med & Surg, Stockholm, Sweden..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Östman, Arne
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36149Article in journal (Refereed)
    Abstract [en]

    The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment. Comparative analyses demonstrated that MF metrics out-performed standard histomorphological features such as tumor grade, budding and configuration of invasive front. Notably, the MF analyses-derived "alpha(max)" -metric constitutes the first response-predictive biomarker in stage II-III colon cancer showing significant interactions with treatment in analyses using a randomized trial-derived study population. Based on these results the method appears as an attractive and easy-to-implement tool for biomarker identification.

  • 283.
    Micke, Patrick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mattsson, Johanna Sofia Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Planck, Maria
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22100 Lund, Sweden;Skane Univ Hosp, Dept Resp Med & Allergol, SE-22185 Lund, Sweden.
    Tran, Lena
    Region Skane, Div Lab Med, Dept Genet & Pathol, SE-22185 Lund, Sweden.
    Vidarsdottir, Halla
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22100 Lund, Sweden;Helsingborg Hosp, Dept Surg, SE-25187 Helsingborg, Sweden.
    Nodin, Bjorn
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22100 Lund, Sweden.
    Jirstrom, Karin
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22100 Lund, Sweden;Region Skane, Div Lab Med, Dept Genet & Pathol, SE-22185 Lund, Sweden.
    Brunnstrom, Hans
    Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, SE-22100 Lund, Sweden;Region Skane, Div Lab Med, Dept Genet & Pathol, SE-22185 Lund, Sweden.
    Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1319Article in journal (Refereed)
    Abstract [en]

    Accurate diagnosis of histological type is important for therapy selection in lung cancer. Immunohistochemical (IHC) and histochemical stains are often used to complement morphology for definite diagnosis and are incorporated in the WHO classification. Our main aim was to compare different mucin stains and assess their value in relation to common IHC analyses in lung cancer diagnostics. Using tissue microarrays from 657 surgically treated primary lung cancers, we evaluated the mucin stains periodic acid-Schiff with diastase (PASD), alcian blue-periodic acid-Schiff (ABPAS) and mucicarmine, and compared with the IHC markers p40, p63, cytokeratin 5, thyroid transcription factor 1 (TTF-1), napsin A and cytokeratin 7. Ten or more cytoplasmic mucin inclusions in a tissue microarray core were seen in 51%, 48% and 31% of the 416 adenocarcinomas and 3%, 4% and 0.5% of the 194 squamous cell carcinomas with PASD, ABPAS and mucicarmine, respectively. Diagnostic pitfalls, such as entrapped benign epithelium, apoptotic/necrotic cells and glycogen, partly differed for the mucin stains. TTF-1 and napsin A IHC stainings had similar specificity but better sensitivity for adenocarcinoma than the mucin stains, but addition of PASD or ABPAS identified more tumors as adenocarcinomas (n = 8 and n = 10, respectively) than napsin A (n = 1) in cases with solid growth that were negative for TTF-1 and p40. We conclude that PASD and ABPAS have similar diagnostic performance and that these markers are of value in poorly differentiated cases. However, morphology and TTF-1 and p40 IHC staining is sufficient for correct diagnosis in most non-small cell lung cancers.

  • 284.
    Mir, Showkat H.
    et al.
    Cent Univ Gujarat, Ctr Nano Sci, Gandhinagar 382030, India..
    Jha, Prakash C.
    Cent Univ Gujarat, Sch Chem Sci, Gandhinagar 382030, India..
    Islam, Muhammed Shafiqul
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Banarjee, Amitava
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Luo, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Dabhi, Shweta D.
    Maharaja Krishnakumarsinhji Bhavnagar Univ, Dept Phys, Bhavnagar 364001, Gujarat, India..
    Jha, Prafulla K.
    Maharaja Sayajirao Univ Baroda, Dept Phys, Fac Sci, Vadodara 390002, India..
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Static and Dynamical Properties of heavy actinide Monopnictides of Lutetium2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 29309Article in journal (Refereed)
    Abstract [en]

    In this work, density functional theory within the framework of generalized gradient approximation has been used to investigate the structural, elastic, mechanical, and phonon properties of lutetium monopnictides in rock-salt crystal structure. The spin orbit coupling and Hubbard-U corrections are included to correctly predict the essential properties of these compounds. The elastic constants, Young's modulus E, Poisson's ratio v, shear modulus G, anisotropy factor A and Pugh's ratio are computed. We found that all lutetium monopnictides are anisotropic and show brittle character. From the wave velocities along [100], [110] and [111] directions, melting temperature of lutetium monopnictides are predicted. Dynamical stability of these monopnictides has been studied by density functional perturbation theory.

  • 285.
    Mobarrez, Fariborz
    et al.
    Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Vikerfors, Anna
    Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Gustafsson, Johanna T.
    Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Gunnarsson, Iva
    Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden..
    Zickert, Agneta
    Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Larsson, Anders
    Akad Hosp, Dept Clin Chem & Pharmacol, SE-75185 Uppsala, Sweden.
    Pisetsky, David S.
    Department of Medicine, Duke University Medical Center; Medical Research Service, Durham VA Hospital, NC, USA..
    Wallén, Håkan
    Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden..
    Svenungsson, Elisabet
    Unit of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden..
    Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 36025Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS(+)/PS(-)), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2-10 times more abundant in SLE blood compared to controls. PS(-) MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS(-) MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS(-) MPs, suggests a generalized disturbance in SLE. MPs may be regarded as "liquid biopsies" to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis.

  • 286.
    Molin, Carl Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Westerberg, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 39716Article in journal (Refereed)
    Abstract [en]

    This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.

  • 287.
    Monard, C.
    et al.
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Uppsala BioCtr, POB 7026, SE-75007 Uppsala, Sweden; Univ Rennes 1, UMR ECOBIO 6553, OSUR, CNRS, F-35042 Rennes, France.
    Gantner, Stephan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Uppsala BioCtr, POB 7026, SE-75007 Uppsala, Sweden; Rhein Akad Koln, Vogelsanger Str 295, D-50825 Cologne, Germany.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Hallin, S.
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Uppsala BioCtr, POB 7026, SE-75007 Uppsala, Sweden.
    Stenlid, J.
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, Uppsala BioCtr, POB 7026, SE-75007 Uppsala, Sweden.
    Habitat generalists and specialists in microbial communities across a terrestrial-freshwater gradient2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37719Article in journal (Refereed)
    Abstract [en]

    Observations of distributions of microorganisms and their differences in community composition across habitats provide evidence of biogeographical patterns. However, little is known about the processes controlling transfers across habitat gradients. By analysing the overall microbial community composition (bacteria, fungi, archaea) across a terrestrial-freshwater gradient, the aim of this study was to understand the spatial distribution patterns of populations and identify taxa capable of crossing biome borders. Barcoded 454 pyrosequencing of taxonomic gene markers was used to describe the microbial communities in adjacent soil, freshwater and sediment samples and study the role of biotic and spatial factors in shaping their composition. Few habitat generalists but a high number of specialists were detected indicating that microbial community composition was mainly regulated by species sorting and niche partitioning. Biotic interactions within microbial groups based on an association network underlined the importance of ActinobacteriaSordariomycetesAgaricomycetes and Nitrososphaerales in connecting among biomes. Even if dispersion seemed limited, the shore of the lake represented a transition area, allowing populations to cross the biome boundaries. In finding few broadly distributed populations, our study points to biome specialization within microbial communities with limited potential for dispersal and colonization of new habitats along the terrestrial-freshwater continuum.

  • 288.
    Monazzam, Azita
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Li, Su-Chen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Razmara, Masoud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Rosenström, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable by [Ga-68]Ga-DO3A-VS-Cys(40)- Exendin-4/PET2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 748Article in journal (Refereed)
    Abstract [en]

    Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.

  • 289.
    Morris, Julia
    et al.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Bailey, Mark E. S.
    Univ Glasgow, Coll Med Vet & Life Sci, Sch Life Sci, Glasgow, Lanark, Scotland.
    Baldassarre, Damiano
    Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy;IRCCS, Ctr Cardiol Monzino, Milan, Italy.
    Cullen, Breda
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden.
    Ferguson, Amy
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden;Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden.
    Giral, Philippe
    Grp Hop Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France.
    Goel, Anuj
    Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England;Univ Oxford, Wellcome Ctr Human Genet, Oxford, England.
    Graham, Nicholas
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Humphries, Steve E.
    UCL, Ctr Cardiovasc Genet, Inst Cardiovasc Sci, London, England.
    Johnston, Keira J. A.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland;Univ Glasgow, Coll Med Vet & Life Sci, Sch Life Sci, Glasgow, Lanark, Scotland;Univ Edinburgh, Coll Med, Div Psychiat, Edinburgh, Midlothian, Scotland.
    Lyall, Donald M.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Lyall, Laura M.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Sennblad, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden.
    Silveira, Angela
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Smit, Andries J.
    Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands;Univ Groningen, Groningen, Netherlands.
    Tremoli, Elena
    IRCCS, Ctr Cardiol Monzino, Milan, Italy;Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, Milan, Italy.
    Ward, Joey
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Watkins, Hugh
    Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England;Univ Oxford, Wellcome Ctr Human Genet, Oxford, England.
    Smith, Daniel J.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Strawbridge, Rona J.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland;Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Genetic variation in CADM2 as a link between psychological traits and obesity2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7339Article in journal (Refereed)
    Abstract [en]

    CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p < 1 x 10(-5)) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p < 1 x 10(-5)) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.

  • 290.
    Mourik, Bas C.
    et al.
    Erasmus Univ, Dept Med Microbiol & Infect Dis, Med Ctr, Rotterdam, Netherlands..
    Svensson, Robin J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    de Knegt, Gerjo J.
    Erasmus Univ, Dept Med Microbiol & Infect Dis, Med Ctr, Rotterdam, Netherlands..
    Bax, Hannelore I.
    Erasmus Univ, Sect Infect Dis, Dept Internal Med, Med Ctr, Rotterdam, Netherlands..
    Verbon, Annelies
    Erasmus Univ, Sect Infect Dis, Dept Internal Med, Med Ctr, Rotterdam, Netherlands..
    Simonsson, Ulrika S H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    de Steenwinkel, Jurriaan E. M.
    Erasmus Univ, Dept Med Microbiol & Infect Dis, Med Ctr, Rotterdam, Netherlands..
    Improving treatment outcome assessment in a mouse tuberculosis model2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 5714Article in journal (Refereed)
    Abstract [en]

    Preclinical treatment outcome evaluation of tuberculosis (TB) occurs primarily in mice. Current designs compare relapse rates of different regimens at selected time points, but lack information about the correlation between treatment length and treatment outcome, which is required to efficiently estimate a regimens' treatment-shortening potential. Therefore we developed a new approach. BALB/c mice were infected with a Mycobacterium tuberculosis Beijing genotype strain and were treated with rifapentine-pyrazinamide-isoniazid-ethambutol (R(p)ZHE), rifampicin-pyrazinamide-moxifloxacin-ethambutol (RZME) or rifampicin-pyrazinamide-moxifloxacin-isoniazid (RZMH). Treatment outcome was assessed in n = 3 mice after 9 different treatment lengths between 2-6 months. Next, we created a mathematical model that best fitted the observational data and used this for inter-regimen comparison. The observed data were best described by a sigmoidal E-max model in favor over linear or conventional E-max models. Estimating regimen-specific parameters showed significantly higher curative potentials for RZME and R(p)ZHE compared to RZMH. In conclusion, we provide a new design for treatment outcome evaluation in a mouse TB model, which (i) provides accurate tools for assessment of the relationship between treatment length and predicted cure, (ii) allows for efficient comparison between regimens and (iii) adheres to the reduction and refinement principles of laboratory animal use.

  • 291.
    Mubanga, Mwenya
    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.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nowak, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    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.
    Dog ownership and the risk of cardiovascular disease and death: a nationwide cohort study2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 15821Article in journal (Refereed)
    Abstract [en]

    Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65-0.69) and 0.89 (0.87-0.91), respectively; and CVD death, HR 0.64 (0.59-0.70), and 0.85 (0.81-0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89-0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.

  • 292.
    Mueller, Vilhelm
    et al.
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Rajer, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Frykholm, Karolin
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Nyberg, Lena K.
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Quaderi, Saair
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden.;Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Fritzsche, Joachim
    Chalmers, Dept Appl Phys, Gothenburg, Sweden..
    Kristiansson, Erik
    Univ Gothenburg, Chalmers Univ Technol, Dept Math Sci, Gothenburg, Sweden.;Univ Gothenburg, Ctr Antibiot Resistance Res CARe, Gothenburg, Sweden..
    Ambjornsson, Tobias
    Lund Univ, Dept Astron & Theoret Phys, Lund, Sweden..
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Westerlund, Fredrik
    Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37938Article in journal (Refereed)
    Abstract [en]

    Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples.

  • 293.
    Murali, Mrinal
    et al.
    Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Hofman, Paul L.
    Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Derraik, Jose G. B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Auckland, Better Start Natl Sci Challenge, Auckland, New Zealand;Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Cutfield, Wayne S.
    Univ Auckland, Better Start Natl Sci Challenge, Auckland, New Zealand;Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Hornung, Tim
    Starship Childrens Hosp, Dept Paediat Cardiol, Auckland, New Zealand.
    Gusso, Silmara
    Univ Auckland, Liggins Inst, Auckland, New Zealand.
    Exercise capacity and cardiac function in adolescents born post-term2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 12963Article in journal (Refereed)
    Abstract [en]

    There is some evidence that children born post-term (>= 42 weeks of gestation) have metabolic abnormalities that may be associated with an increased risk of adverse health outcomes in adulthood. However, there are no data as to whether adolescents born post-term display alterations in aerobic capacity or cardiovascular function. We studied 48 adolescents (56% males) in Auckland (New Zealand) with a mean age of 14.3 years (SD = 1.7): 25 born post-term and 23 born at term (37-41 weeks of gestation). Assessments included metabolic markers in blood, whole body DXA scans, 24-hour ambulatory blood pressure monitoring, maximal exercise capacity, as well as cardiac MRI scan at rest and during submaximal exercise. Exercise capacity was lower in the post-term than in control participants (44.5 vs 47.8 ml/kgffm/min; p = 0.04). There were no differences in left ventricular volumes at rest and during exercise between groups. The 24-hour ambulatory blood pressure monitoring also showed no differences between the two groups. Being born post-term was associated with reduced exercise capacity, but with no observed differences in central cardiac function. We speculate that the reduction in exercise capacity may be due to changes in the peripheral vascular system.

  • 294.
    Murer, Fredrik K.
    et al.
    Norwegian Univ Sci & Technol, Dept Phys, Hgsk Ringen 5, N-7491 Trondheim, Norway.
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. UPMC, CNRS, Sorbonne Univ, CR2P,MNHN, 57 Rue Cuvier,CP38, F-75005 Paris, France;ESRF, 71 Ave Martyrs, F-38000 Grenoble, France.
    Alvarez-Murga, Michelle
    ESRF, 71 Ave Martyrs, F-38000 Grenoble, France.
    Di Michiel, Marco
    ESRF, 71 Ave Martyrs, F-38000 Grenoble, France.
    Pfeiffer, Franz
    Tech Univ Munich, Lehrstuhl Biomed Phys, Dept Phys, D-85748 Garching, Germany;Tech Univ Munich, Inst Med Tech, D-85748 Garching, Germany;Tech Univ Munich, Klinikum Rechts Isar, Dept Diagnost & Intervent Radiol, D-81675 Munich, Germany.
    Bech, Martin
    Lund Univ, Dept Med Radiat Phys, Clin Sci, S-22185 Lund, Sweden.
    Breiby, Dag W.
    Univ South Eastern Norway, Dept Microsyst, N-3184 Borre, Norway;Norwegian Univ Sci & Technol, Dept Phys, Hgsk Ringen 5, N-7491 Trondheim, Norway.
    3D Maps of Mineral Composition and Hydroxyapatite Orientation in Fossil Bone Samples Obtained by X-ray Diffraction Computed Tomography2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 10052Article in journal (Refereed)
    Abstract [en]

    Whether hydroxyapatite (HA) orientation in fossilised bone samples can be non-destructively retrieved and used to determine the arrangement of the bone matrix and the location of muscle attachments (entheses), is a question of high relevance to palaeontology, as it facilitates a detailed understanding of the (micro-)anatomy of extinct species with no damage to the precious fossil specimens. Here, we report studies of two fossil bone samples, specifically the tibia of a 300-million-year-old tetrapod, Discosauriscus austriacus, and the humerus of a 370-million-year-old lobe-finned fish, Eusthenopteron foordi, using XRD-CT - a combination of X-ray diffraction (XRD) and computed tomography (CT). Reconstructed 3D images showing the spatial mineral distributions and the local orientation of HA were obtained. For Discosauriscus austriacus, details of the muscle attachments could be discerned. For Eusthenopteron foordi, the gross details of the preferred orientation of HA were deduced using three tomographic datasets obtained with orthogonally oriented rotation axes. For both samples, the HA in the bone matrix exhibited preferred orientation, with the unit cell c-axis of the HA crystallites tending to be parallel with the bone surface. In summary, we have demonstrated that XRD-CT combined with an intuitive reconstruction procedure is becoming a powerful tool for studying palaeontological samples.

  • 295.
    Mäe, Maarja Andaloussi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Li, Tian
    Karolinska Inst, Dept Med, Integrated Cardiometab Ctr, Huddinge, Sweden.
    Bertuzzi, Giacomo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Univ Oxford, Physiol Anat & Genet, Sherrington Bldg,Pk Rd, Oxford, England.
    Raschperger, Elisabeth
    Karolinska Inst, Dept Med, Integrated Cardiometab Ctr, Huddinge, Sweden.
    Vanlandewijck, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, Dept Med, Integrated Cardiometab Ctr, Huddinge, Sweden.
    He, Liqun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Tianjin Med Univ, Gen Hosp, Key Lab Postneuroinjury Neurorepair & Regenerat C, Minist Educ,Tianjin Neurol Inst,Dept Neurosurg, Tianjin, Peoples R China.
    Nahar, Khayrun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Dalheim, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Loyola Univ, Cardinal Bernardin Canc Ctr, Dept Surg, Chicago, IL 60611 USA.
    Hofmann, Jennifer J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Concordia Univ, Austin, TX USA.
    Lavina, Barbara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Keller, Annika
    Zurich Univ, Dept Neurosurg, Clin Neuroctr, Univ Zurich Hosp, Zurich, Switzerland.
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Karolinska Inst, Dept Med, Integrated Cardiometab Ctr, Huddinge, Sweden.
    Genove, Guillem
    Karolinska Inst, Dept Med, Integrated Cardiometab Ctr, Huddinge, Sweden.
    Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17462Article in journal (Refereed)
    Abstract [en]

    Diabetes mellitus is associated with cognitive impairment and various central nervous system pathologies such as stroke, vascular dementia, or Alzheimer's disease. The exact pathophysiology of these conditions is poorly understood. Recent reports suggest that hyperglycemia causes cerebral microcirculation pathology and blood-brain barrier (BBB) dysfunction and leakage. The majority of these reports, however, are based on methods including in vitro BBB modeling or streptozotocininduced diabetes in rodents, opening questions regarding the translation of the in vitro findings to the in vivo situation, and possible direct effects of streptozotocin on the brain vasculature. Here we used a genetic mouse model of hyperglycemia (Ins2(AKITA)) to address whether prolonged systemic hyperglycemia induces BBB dysfunction and leakage. We applied a variety of methodologies to carefully evaluate BBB function and cellular integrity in vivo, including the quantification and visualization of specific tracers and evaluation of transcriptional and morphological changes in the BBB and its supporting cellular components. These experiments did neither reveal altered BBB permeability nor morphological changes of the brain vasculature in hyperglycemic mice. We conclude that prolonged hyperglycemia does not lead to BBB dysfunction, and thus the cognitive impairment observed in diabetes may have other causes.

  • 296.
    Natchimuthu, Sivakiruthika
    et al.
    Linkoping Univ, Dept Themat Studies Environm Change, S-58183 Linkoping, Sweden.
    Wallin, Marcus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Klemedtsson, Leif
    Univ Gothenburg, Dept Earth Sci, S-40530 Gothenburg, Sweden.
    Bastviken, David
    Linkoping Univ, Dept Themat Studies Environm Change, S-58183 Linkoping, Sweden.
    Spatio-temporal patterns of stream methane and carbon dioxide emissions in a hemiboreal catchment in Southwest Sweden2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 39729Article in journal (Refereed)
    Abstract [en]

    Global stream and river greenhouse gas emissions seem to be as large as the oceanic C uptake. However, stream and river emissions are uncertain until both spatial and temporal variability have been quantified. Here we investigated in detail the stream CH4 and CO2emissions within a hemiboreal catchment in Southwest Sweden primarily covered by coniferous forest. Gas transfer velocities (k600), CH4 and CO2 concentrations were measured with multiple methods. Our data supported modelling approaches accounting for various stream slopes, water velocities and discharge. The results revealed large but partially predictable spatio-temporal variabilities in k600, dissolved gas concentrations, and emissions. The variability in CO2 emission was best explained by the variability in k, while dissolved CH4concentrations explained most of the variability in CH4 emission, having implications for future measurements. There were disproportionately large emissions from high slope stream reaches including waterfalls, and from high discharge events. In the catchment, stream reaches with low slope and time periods of moderate discharge dominated (90% of area and 69% of time). Measurements in these stream areas and time periods only accounted for <36% of the total estimated emissions. Hence, not accounting for local or episodic high emissions can lead to substantially underestimated emissions.

  • 297.
    Negi, Devendra Singh
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Idrobo, Juan Carlos
    Ctr Nanophase Mat Sci, Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA..
    Rusz, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Probing the localization of magnetic dichroism by atomic-size astigmatic and vortex electron beams2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 4019Article in journal (Refereed)
    Abstract [en]

    We report localization of a magnetic dichroic signal on atomic columns in electron magnetic circular dichroism ( EMCD), probed by beam distorted by four-fold astigmatism and electron vortex beam. With astigmatic probe, magnetic signal to noise ratio can be enhanced by blocking the intensity from the central part of probe. However, the simulations show that for atomic resolution magnetic measurements, vortex beam is a more effective probe, with much higher magnetic signal to noise ratio. For all considered beam shapes, the optimal SNR constrains the signal detection at low collection angles of approximately 6-8 mrad. Irrespective of the material thickness, the magnetic signal remains strongly localized within the probed atomic column with vortex beam, whereas for astigmatic probes, the magnetic signal originates mostly from the nearest neighbor atomic columns. Due to excellent signal localization at probing individual atomic columns, vortex beams are predicted to be a strong candidate for studying the crystal site specific magnetic properties, magnetic properties at interfaces, or magnetism arising from individual atomic impurities.

  • 298.
    Netzer, Nathan L.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Must, Indrek
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Qiao, Yupu
    Univ South Dakota, Dept Chem, 414 E Clark St, Vermillion, SD 57069 USA..
    Zhang, Shi-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Wang, Zhenqiang
    Univ South Dakota, Dept Chem, 414 E Clark St, Vermillion, SD 57069 USA..
    Zhang, Zhen
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Biomimetic supercontainers for size-selective electrochemical sensing of molecular ions2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 45786Article in journal (Refereed)
    Abstract [en]

    New ionophores are essential for advancing the art of selective ion sensing. Metal-organic supercontainers (MOSCs), a new family of biomimetic coordination capsules designed using sulfonylcalix[4] arenes as container precursors, are known for their tunable molecular recognition capabilities towards an array of guests. Herein, we demonstrate the use of MOSCs as a new class of size-selective ionophores dedicated to electrochemical sensing of molecular ions. Specifically, a MOSC molecule with its cavities matching the size of methylene blue (MB+), a versatile organic molecule used for bio-recognition, was incorporated into a polymeric mixed-matrix membrane and used as an ion-selective electrode. This MOSC-incorporated electrode showed a near-Nernstian potentiometric response to MB+ in the nano-to micro-molar range. The exceptional size-selectivity was also evident through contrast studies. To demonstrate the practical utility of our approach, a simulated wastewater experiment was conducted using water from the Fyris River (Sweden). It not only showed a near-Nernstian response to MB+ but also revealed a possible method for potentiometric titration of the redox indicator. Our study thus represents a new paradigm for the rational design of ionophores that can rapidly and precisely monitor molecular ions relevant to environmental, biomedical, and other related areas.

  • 299.
    Neuvonen, Minna M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tamarit, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Näslund, Kristina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Liebig, Juergen
    School of Life Sciences, Arizona State University, Tempe, AZ, 85287, USA..
    Feldhaar, Heike
    Animal Population Ecology, Department of Animal Ecology I, Bayreuth Center of Ecology and Environmental Research (BayCEER), University of Bayreuth, D-95440, Bayreuth, Germany..
    Moran, Nancy A.
    Department of Integrative Biology, University of Texas, Austin, Texas, USA..
    Guy, Lionel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution.
    Andersson, Siv G. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The genome of Rhizobiales bacteria in predatory ants reveals urease gene functions but no genes for nitrogen fixation2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, p. 1-11, article id 39197Article in journal (Refereed)
    Abstract [en]

    Gut-associated microbiota of ants include Rhizobiales bacteria with affiliation to the genus Bartonella. These bacteria may enable the ants to fix atmospheric nitrogen, but no genomes have been sequenced yet to test the hypothesis. Sequence reads from a member of the Rhizobiales were identified in the data collected in a genome project of the ant Harpegnathos saltator. We present an analysis of the closed 1.86 Mb genome of the ant-associated bacterium, for which we suggest the species name Candidatus Tokpelaia hoelldoblerii. A phylogenetic analysis reveals a relationship to Bartonella and Brucella, which infect mammals. Novel gene acquisitions include a gene for a putative extracellular protein of more than 6,000 amino acids secreted by the type I secretion system, which may be involved in attachment to the gut epithelium. No genes for nitrogen fixation could be identified, but genes for a multi-subunit urease protein complex are present in the genome. The urease genes are also present in Brucella, which has a fecal-oral transmission pathway, but not in Bartonella, which use blood-borne transmission pathways. We hypothesize that the gain and loss of the urease function is related to transmission strategies and lifestyle changes in the host-associated members of the Rhizobiales.

  • 300.
    Nguyen, Diem
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden.
    Boberg, Johanna
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden..
    Cleary, Michelle
    Swedish Univ Agr Sci, Southern Swedish Forest Res Ctr, S-23053 Alnarp, Sweden..
    Bruelheide, Helge
    Martin Luther Univ Halle Wittenberg, Inst Biol Geobot & Bot Garden, D-06108 Halle, Germany.;German Ctr Integrat Biodivers Res iDiv, D-04103 Leipzig, Germany..
    Hoenig, Lydia
    Martin Luther Univ Halle Wittenberg, Inst Biol Geobot & Bot Garden, D-06108 Halle, Germany..
    Koricheva, Julia
    Royal Holloway Univ London, Egham TW20 0EX, Surrey, England..
    Stenlid, Jan
    Swedish Univ Agr Sci, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden..
    Foliar fungi of Betula pendula: impact of tree species mixtures and assessment methods2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 41801Article in journal (Refereed)
    Abstract [en]

    Foliar fungi of silver birch (Betula pendula) in an experimental Finnish forest were investigated across a gradient of tree species richness using molecular high-throughput sequencing and visual macroscopic assessment. We hypothesized that the molecular approach detects more fungal taxa than visual assessment, and that there is a relationship among the most common fungal taxa detected by both techniques. Furthermore, we hypothesized that the fungal community composition, diversity, and distribution patterns are affected by changes in tree diversity. Sequencing revealed greater diversity of fungi on birch leaves than the visual assessment method. One species showed a linear relationship between the methods. Species-specific variation in fungal community composition could be partially explained by tree diversity, though overall fungal diversity was not affected by tree diversity. Analysis of specific fungal taxa indicated tree diversity effects at the local neighbourhood scale, where the proportion of birch among neighbouring trees varied, but not at the plot scale. In conclusion, both methods may be used to determine tree diversity effects on the foliar fungal community. However, high-throughput sequencing provided higher resolution of the fungal community, while the visual macroscopic assessment detected functionally active fungal species.

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